As the multiple myeloma treatment paradigm continues to evolve and expand, the navigation of this landscape requires nuance and an understanding that emerging data will continue to reshape the space, according to Ajai Chari, MD.

“When I meet my patients now, I don’t spend too much time prognosticating. I’ll answer their questions, but what I say is, ‘What I tell you today will be obsolete in a year or 2 from now, because that’s how quickly the field is moving,’” Chari said. “That should give patients incredible hope for their future with myeloma, because it’s such an exciting time for clinical research in myeloma.”

Bridging the Gaps in Leukemia, Lymphoma, and Multiple Myeloma Conference

 in 2025, Chari and colleagues published consensus recommendations for the management of multiple myeloma that emerged from the meeting.

 During the meeting, 16 multiple myeloma experts from the United States offered 11 consensus recommendations across smoldering multiple myeloma, frontline therapy, transplant, maintenance, and relapsed/refractory disease management.

, Chari outlined some of the key consensus viewpoints and recommendations featured in the publication.

Chari is a professor of medicine and director of the Multiple Myeloma Program at the University of California, San Francisco.

: With meetings like Bridging the Gaps, what is the importance of having opinions from different experts help inform treatment strategies and recommendations that could be applicable to clinical practice?

: Many people look at the National Comprehensive Cancer Network Guidelines [NCCN] as a barometer of what [they] should do. The problem with that is [the guidelines are] a little overwhelming. I look at NCCN Guidelines as [an outline of treatment options that may be] insurance-approved, but when you have a table with 30 choices, how does that help you at the bedside?

Studies have shown that a patient with myeloma who has contact with an academic center has a better overall survival [OS]. Ideally, we would like to have partnerships where communities are working with academia. The goal of this paper is to try to give practical guidelines in areas that maybe don’t have a clear answer yet, [like for] community oncologists seeing 3 or 4 patients, [where some patients may not be able to travel long distances]. This kind of publication helps fill that gap [that remains with] current guidelines.

I’ll also quickly mention there is a lot of interest in artificial intelligence [AI]. Let’s say I'm giving a talk on a very current topic. AI falls apart at these data gaps. It cannot pull what we might have heard at a [recent] conference or saw in a poster. That’s where this kind of manuscript is helpful, because [some of these recommendations] are not yet in the NCCN Guidelines, and the data may not be in any other paper, so AI doesn’t help you.

Looking at the recommendations in multiple myeloma stemming from Bridging the Gaps, what were some of the key points regarding the management of smoldering myeloma?

The high-level problem with smoldering myeloma is that some patients have monoclonal gammopathy of undetermined significance [MGUS], and some have active myeloma. When you have this clinical definition without biological correlates, you’re throwing darts a little, and that’s why there’s a lot of uncertainty about what to do with this population. We now have data from the phase 3 AQUILA study [NCT03301220] to help guide this decision-making and give an option that’s generally well tolerated [with daratumumab (Darzalex)]. [Data] show a progression-free survival [PFS] and OS benefit [vs surveillance].

 However, the [Bridging the Gaps] group could not reach a consensus on what we should be doing here, and I think it’s because of this heterogeneity. People wanted better risk definitions.

A 2025 expert consensus from Bridging the Gaps highlights the rapid evolution of multiple myeloma care and provides practical guidance to help clinicians navigate complex and expanding treatment options beyond existing guidelines.

While quadruplet therapies are now favored in frontline treatment, uncertainty remains around their use in older patients, the role of stem cell transplant, and duration of maintenance therapy.

Newer targeted treatments, including BCMA-directed therapies and CAR T-cell therapies, show strong benefits, with experts emphasizing early referral, careful sequencing considerations, and infection management to optimize patient outcomes.

One of the problems with smoldering myeloma is, if you take a particular snapshot in time, that’s just a photograph. You need to understand the movie. What was happening prior to this visit? Where was the patient diagnosed? What’s happening after the initial diagnosis? A lot of us would like to see an evolving model incorporated, but AQUILA gives providers and patients an option, particularly for patients who might be older or have comorbidities. We’ll look forward to future versions of this meeting to see if the group is getting closer to a consensus on what to do with this complex topic [in smoldering myeloma].

Regarding the frontline setting for patients with active multiple myeloma, what was the consensus regarding up-front combination approaches and the role of autologous stem cell transplant (ASCT)?

Multiple phase 3 studies have shown that quadruplets are better than triplets, so that [recommendation] was a no-brainer. There’s a joke: If you ask 12 myeloma doctors, you’ll get 20 opinions. But on this, I think everybody agreed. The nuance is: Do frail or older patients need a quadruplet? That’s unclear.

Quadruplets are great, but because their efficacy is so good, the question is: Are we ready to forego ASCT? I don’t think we have a clear answer for that yet. [All patients] should still be considered [for ASCT]. For example, [some] excellent outcomes from quadruplet induction did include transplant.

Delving a little bit deeper into quadruplets, no one's doing twice-weekly bortezomib [Velcade], which is what the studies did, and that's important for practitioners to be aware of. Lastly, you can't say, on the one hand, quadruplet induction, transplant, and maintenance has a projected PFS of 13 to 20 years, and then say everybody needs prolonged, indefinite maintenance therapy. There's a lot of interest in stopping maintenance therapy in standard-risk myeloma with 2 consecutive minimal residual disease [MRD]-negativity [results]. I don't think we need to be giving people 17 years of therapy, and I think the group agreed that we should be starting to drill down on discontinuing therapy.

With the integration of CAR T-cell therapies, bispecific antibodies, antibody-drug conjugates (ADCs], and other combination strategies, in the relapsed/refractory multiple myeloma setting, what were some of the consensus view points on the treatment of this patient population?

We have pivotal phase 3 studies showing that BCMA-directed therapy has beaten standard of care [SOC], and it's important to highlight that these are not the historic triplet vs doublet [regimens]. SOC arms were, in fact, triplets. BCMA is beating SOC, and that's a big message to get across. We should be trying to move these therapies as early as possible, based on the indication and label.

Everybody [at the meeting] agreed, particularly for CAR T-cell therapy, that patients should be referred as early as possible, especially when we start having access to ADCs and bispecifics that could then affect the CAR T outcomes. We don't want to forego a great option for patients without at least having that conversation with the patient and their local doctor.

The other theme that's come up is, if a patient has had a BCMA-directed therapy, it's probably time to switch to a different target, like GPRC5D. Talquetamab-tgvs [Talvey] is [the only GPRC5D-directed agent currently approved for multiple myeloma], but there are other studies going on [with other agents].

With both CAR T-cell therapy and, importantly, bispecifics, when you're targeting BCMA, you get rid of myeloma, but you also get rid of normal plasma cells. Therefore, it's important to prevent infections with IVIG. We would [recommend] 6 months with CAR T-cell therapy and for as long as needed while on bispecifics, even going past that with BCMA-directed bispecifics and IVIG.

Since CAR T-cell therapy referrals require coordination with academic institutions and community practice, what is the importance of early referral?

If you look at, for example, ciltacabtagene autoleucel [cilta-cel; Carvykti], data have shown in advanced myeloma, [the CAR T-cell therapy generates a high] response rate [capable of] lasting 3 or more years with the treatment-free interval. However, from small datasets, the PFS after a prior bispecific targeting BCMA is only approximately 5 months, and after a prior [BCMA-directed] ADC, it is only approximately 9 months. To take a product [like cilta-cel] that is this good and also has cost, using it after these other therapies doesn't make sense from a clinical perspective, a patient perspective, a treatment-free interval perspective, or even a cost perspective.

We're not saying that everybody needs to get CAR T-cell therapy, but that conversation needs to happen at least, because if you get a BCMA-directed CAR T-cell therapy, there are other salvage options down the road that will work, [although] maybe still not as well.

That's the other theme that's come up. So far, it does seem like once you touch BCMA by any modality—ADC, bispecific, or CAR T-cell therapy—it does affect the next effort to target that same antigen, which is why we discussed target switch. What we need to understand more is how fixed-duration treatment or a treatment-free interval after an ADC, bispecific, and a T-cell boosting therapy [affect sequencing].

Right now, we don't have that data, so the message should be: pick up the phone. Call a community doctor, call your academic partner, and say, here's a patient scenario. Would you like to see this person, or should I start something else? As long as that conversation happens, then I think the community doctor can feel good about having checked that box, and then it's up to the referring provider to listen to the [patient and disease] factors that will help guide whether to move forward with an alternative [treatment] or to bring the patient in [for CAR T-cell therapy].

Chari A, Costello C, Krishnan A, et al. Integrating recent evidence and expert perspectives into the management of multiple myeloma: consensus recommendations from the 2025 Bridging the Gaps Conference. 

. Published online April 21, 2026. doi:10.1002/ajh.70339.

Dimopoulos MA, Voorhees PM, Schjesvold F, et al. Daratumumab or active monitoring for high-risk smoldering multiple myeloma. 

. 2025;392(18):1777-1788. doi:10.1056/NEJMoa2409029

Ajai Chari, MD, outlines key consensus viewpoints and recommendations for multiple myeloma management from Bridging the Gaps 2025.

Consensus Viewpoints Offer Guidance in Rapidly Evolving Multiple Myeloma Management

Simlukafusp Alfa Regimens in Metastatic RCC: 

©Image by Ashling Wahner & MJH Life Sciences Using AI

The novel immunocytokine simlukafusp alfa (FAP-IL2v) combined with atezolizumab (Tecentriq), with or without bevacizumab (Avastin), demonstrated a manageable safety profile and encouraging antitumor activity in patients with unresectable, metastatic renal cell carcinoma (RCC), according to results from a phase 1b study (NCT03063762) published in the 

Among patients receiving the doublet (n = 28) the objective response rate (ORR) was 25.0% (90% CI, 14.2%-40.2%), the disease control rate (DCR) was 60.7% (90% CI, 45.2%-74.3%), and the median duration of response (DOR) was not estimable (NE; 95% CI, 15.3 months to NE). The median progression-free survival (PFS) with the doublet was 6.3 months (95% CI, 1.9-18.2).

The triplet regimen (n = 38) yielded an ORR of 47.4% (90% CI, 34.7%-60.4%), a DCR of 89.5% (90% CI, 78.5%-95.2%), and a median DOR of NE (95% CI, 12.6 months to NE). The median PFS with the triplet was 18.3 months (95% CI, 11.0–22.1).

Although the triplet therapy demonstrated greater clinical activity across key parameters, the investigators noted that formal statistical comparisons between arms were not performed.

“The combination of [simlukafusp alfa] plus atezolizumab with or without bevacizumab did not improve response rates, as compared with current standard therapy for metastatic RCC,” Jose Luis Perez-Gracia, MD, PhD, a consultant oncologist at Clinica Universidad de Navarra, Pamplona, Spain, and his coauthors wrote in the publication.

The novel immunocytokine simlukafusp alfa plus atezolizumab, with or without bevacizumab, demonstrated a manageable safety profile and antitumor activity in patients with unresectable, mRCC.

However, the doublet and triplet regimens did not improve response rates compared with standard therapies.

Pharmacodynamic results confirmed the ability of IL-2–based therapies to induce an inflammatory infiltrate, supporting continued research of IL-2–based therapies and other novel immunocytokines in mRCC.

The randomized, multicenter, open-label phase Ib study enrolled adult patients with confirmed unresectable advanced/metastatic RCC with a component of clear cell and/or sarcomatoid histology.

 Patients were also required to have measurable disease per RECIST 1.1 criteria, an ECOG performance status of 0 or 1, an evaluable Memorial Sloan-Kettering Cancer Center risk score, and a life expectancy of at least 12 weeks.

The phase Ib study comprised 2 parts: a dose-escalation phase using a 3+3 design and a dose-extension phase. During dose escalation, patients with unresectable metastatic RCC who had received up to 1 prior systemic therapy were enrolled. All patients received simlukafusp alfa plus atezolizumab during cycle 1 before random assignment to either the doublet arm (arm A: simlukafusp alfa plus atezolizumab every 2 weeks) or the triplet arm (arm B: simlukafusp alfa plus atezolizumab and bevacizumab every 2 weeks). During dose-extension, treatment-naive patients were randomly assigned receive the doublet or triplet as a twice-weekly dose (arms A and B) or 3 times a week (arms C and D).

The recommended dose of simlukafusp was 10 mg; this dose was selected for the extension phase based on the previously established monotherapy dose, potential additive toxicity from combination therapy, and evidence that 10 mg generated profound lymphocyte expansion and activation. The maximum tolerated dose (MTD) was not reached.

The study’s primary end points were the incidence of dose-limiting toxicities, determining the MTD of simlukafusp alfa, determining the recommended dose of simlukafusp alfa, and ORR. Secondary end points included pharmacokinetic measures, DCR, complete response rate, DOR, PFS, and overall survival.

What were the pharmacokinetic and safety data that were shared in the publication?

In terms of safety, all 66 patients experienced at least 1 adverse effect (AE) considered related to simlukafusp alfa, the most common of which were pyrexia (83%), chills (68%), and nausea (52%). Serious AEs occurred in 58% of patients overall, 47% of which were considered related to any study drug.

Expected IL-2 class–specific AEs were observed, including liver function test abnormalities (70%), infusion-related reactions (38%), and hypotension (15%). Notably, no cases of capillary leak syndrome were reported. Only 3 cases of serious treatment-related hypotension, all of which were grade 3, were documented.

Two treatment-related deaths were recorded: 1 from grade 5 acute kidney injury (arm A, attributed to simlukafusp alfa and atezolizumab) and another from pancytopenia that occurred 236 days after the last dose of study treatment. A third death, from grade 5 hemothorax in arm D, was considered possibly related to antiplatelet treatment. Rates of AEs leading to simlukafusp alfa dose interruption or modification were 61% during dose escalation and 53% during dose extension.

Pharmacodynamic analyses supported the mechanism of action of IL-2. In peripheral blood, simlukafusp alfa induced pronounced and sustained expansion of natural killer (NK) cells, CD8-positive T cells, and CD4-positive T cells. Peripheral regulatory T cell (Treg) levels remained unchanged, consistent with simlukafusp alfa‘s engineered selectivity away from Treg activation. Expansion of immune cell populations in early cycles was accompanied by elevated levels of soluble CD25, a marker of sustained systemic immune activation.

In paired tumor biopsies from 18 patients in arms A and B, a significant increase in T effector signature score was observed on-treatment vs baseline (

 = .002). Marked increases in tumor-infiltrating lymphocyte density, including CD3-positive and CD8-positive T cells, proliferating CD8-positive T cells, and perforin-positive cytotoxic T and NK cells, were documented following both regimens. Responders demonstrated more pronounced on-treatment changes in tumor tissue compared with non-responders, particularly for CD3-positive T cells and NK cells.

“Our results do not support further development of [simlukafusp alfa] in this setting. However, our pharmacodynamic results confirm the ability of IL-2–based therapies to induce an inflammatory infiltrate, supporting continued research of IL-2–based therapies and other novel immunocytokines in metastatic RCC,” Perez-Gracia and his coauthors wrote in their conclusion.

Perez-Gracia JL, Mellado B, Hansen AR, et al. Simlukafusp alfa (FAP-IL2v) plus atezolizumab with or without bevacizumab in unresectable, metastatic renal cell carcinoma: a randomized, open-label phase Ib study. 

. 2026;14(4):e012466. doi:10.1136/jitc-2025-012466

Study to evaluate safety, pharmacokinetics and therapeutic activity of RO6874281 as a combination therapy in participants with unresectable advanced and/​or metastatic renal cell carcinoma (RCC). ClinicalTrials.gov. Updated February 17, 2023. Accessed May 5, 2026. https://clinicaltrials.gov/study/NCT03063762

Simlukafusp alfa (FAP-IL2v) plus atezolizumab, with or without bevacizumab, showed manageable but IL-2–class toxicity and pharmacodynamic evidence of robust effector immune activation in unresectable/metastatic RCC. Clinical activity favored the bevacizumab-containing triplet, with higher ORR (47.4% vs 25.0%) and longer median PFS (18.3 vs 6.3 months), while DOR was not estimable in both arms. Despite tumor and peripheral immune-infiltrate augmentation, response rates did not exceed contemporary standards, limiting further development in this setting.

Simlukafusp alfa plus atezolizumab with/without bevacizumab was safe and active but did not improve upon responses with SOC treatments in metastatic RCC.

Simlukafusp Alfa Regimens Show Manageable Safety and Activity But Do Not Outperform SOC in Metastatic RCC

The investigational fourth-generation EGFR inhibitor HS-10504 demonstrated encouraging efficacy and a manageable safety profile at the 400-mg dose in patients with advanced 

-mutant non–small cell lung cancer (NSCLC) harboring the C797S resistance mutation, according to initial data from the phase 1 first-in-human HS-10504-101 trial (NCT06461156) that were presented at the 

“HS-10504 monotherapy demonstrated an encouraging result in [patients with] advanced NSCLC harboring the C797S mutation post EGFR TKI treatment,” Zhanhong Xie, MD, lead study author and faculty within the Department of Respiratory and Critical Care Medicine and the Department of Oncology at The First Affiliated Hospital of Guangzhou Medical University in China, said in a presentation of the data. “Promising efficacy results [were seen] in a high unmet need population,” Xie added. 

Promising response rates were seen in pretreated patients with 

The agent is designed to target C797S resistance mutation after TKI failure.

Continuous daily dosing proved feasible and was associated with a manageable safety profile.

What makes HS-10504 a next-generation EGFR inhibitor?

Osimertinib’s (Tagrisso) role as a frontline standard of care for patients with 

-mutant advanced NSCLC has been upheld by data showing significantly improved progression-free survival (PFS) and overall survival (OS) vs first-generation EGFR TKIs. However, responses wane in the face of acquired resistance and development of progressive disease (PD).

The primary resistance mutation associated with the use of osimertinib in either the first or second-line setting is C797S, present in approximately 7% and 14% of cases, respectively. The mutation has also been documented with the use of other third-generation EGFR TKIs such as aumolertinib and furmonertinib.

HS-10504 is a novel, potent, fourth-generation EGFR TKI that is highly selective for 

sensitizing mutations and the C797S resistance mutation, with or without a concomitant T790M mutation.

The single-arm, open-label, multicenter study enrolled patients with histologically or cytologically confirmed locally advanced or metastatic stage IIIB, IIIC, IV, or above NSCLC. An 

 sensitizing mutation––either exon 19 deletion or L858R mutation––and a C797S mutation with or without a T790M mutation was required, alongside at least 1 target lesion according to RECIST 1.1 criteria and an ECOG performance status of 0 or 1.

In part 1 dose escalation a rolling 6 design was used to evaluate the following doses of HS-10504: 50 mg (n = 1), 100 mg (n = 4), 200 mg (n = 4), 300 mg (n = 3), 400 mg (n = 5), and 500 mg (n = 4).

In part 2 dose expansion two dose levels were evaluated: 300 mg (n = 31) and 400 mg (n = 30).

The primary end point was the maximum tolerated dose or maximum applicable dose.

 Secondary end points included safety, pharmacokinetics, objective response rate (ORR), disease control rate (DCR), duration of response (DOR), PFS, and OS.

Treatment was administered orally, once daily on a continuous basis until disease progression or other criteria for discontinuation were met.

Who were the patients enrolled in this study?

Baseline characteristics were presented in the dose expansion population of patients who received HS-10504 at either 300 mg (n = 34) or 400 mg (n = 35). In the former population, the median age was 63.5 years (range, 37-78) and most patients were female (n = 19; 55.9%) and had stage IVB disease (n = 23; 67.6%) according to the American Joint Committee on Cancer (AJCC) 8th edition staging manual. ECOG performance status was largely 1 (n = 28; 82.4%) and most patients had a concomitant T790M mutation (n = 19; 55.9%). Central nervous system (CNS) metastases were found in the minority of patients (n = 6; 17.6%) as was prior exposure to chemotherapy (n = 10; 29.4%). With respect to prior treatment, patients had either received 1 (n = 13; 38.2%), 2 (n = 16; 47.1%), or 3 or more (n = 5; 14.7%) lines.

In the latter population the median age was 61.0 years (range, 35-78) and most patients were female (n = 25; 71.4%) and had stage IVB disease (n = 19; 54.3%) according to the AJCC 8th edition staging manual. ECOG performance status was largely 1 (n = 30; 85.7%) and most patients did not have a concomitant T790M mutation (n = 20; 57.1%). CNS metastases were found in the minority of patients (n = 6; 17.1%) as was prior exposure to chemotherapy (n = 14; 40.0%). With respect to prior treatment, patients had either received 1 (n = 13; 37.1%), 2 (n = 13; 37.1%), or 3 or more (n = 9; 25.7%) lines.

How safe and tolerable is HS-10504 at different dose levels?

The 400-mg dose was found to be manageable, Xie said, with most adverse effects (AEs) resolving after symptom management and/or dose interruption or modification. Only 1 patient discontinued treatment because of treatment-related AEs (TRAEs), supporting continuous dosing.

Median follow-up was 3.1 months (range, 0.1-11.5) and 5.3 months (range, 0.9-9.0) in the 300-mg and 400-mg cohorts, respectively. In the former population, any AEs, grade 3 or greater AEs, and any serious AEs occurred at rates of 91.2% (n = 31), 35.3% (n = 12), and 5.9% (n = 2), respectively. AEs led to treatment interruption in 20.6% (n = 7) of patients, and no events led to treatment reduction, discontinuation, or death. In the latter population, any AEs, grade 3 or greater AEs, and any serious AEs occurred at rates of 100.0% (n = 35), 65.7% (n = 23), and 31.4% (n = 11), respectively. AEs leading to treatment interruption, reduction, and discontinuation occurred at rates of 40.0% (n = 14), 42.9% (n = 15), and 2.9% (n = 1), respectively. No events led to death.

Common TRAEs that occurred in at least 25% of patients and grade 3 or greater TRAEs were also presented for the 400-mg dose cohort. Xie shared that most TRAEs were grade 1 or 2 and most grade 3 events that occurred in at least 10% of patients included decreased lymphocyte count (n = 11; 31.4%) and anemia (n = 5; 14.3%).

Any-grade and grade 3 or greater TRAEs, respectively, included increased blood bilirubin (82.9%; 5.7%), anemia (60.0%; 14.3%), increased alanine aminotransferase levels (57.1%; 2.9%), rash (54.3%; 0%), increased aspartate aminotransferase levels (48.6%; 0%), decreased lymphocyte count (45.7%; 31.4%), diarrhea (42.9%; 2.9%), decreased appetite (40.0%; 2.9%), increased blood creatinine (40.0%; 0%), hypoalbuminemia (37.1%; 0%), decreased white blood cell count (31.4%; 2.9%), hypokalemia (28.6%; 8.6%), increased blood urea (28.6%; 0%), increased conjugated bilirubin (28.6%; 2.9%), increased blood lactate dehydrogenase (25.7%; 0%), increased blood creatine phosphokinase (25.7%; 2.9%), and asthenia (25.7%; 0%).

What were the key response rates at 300 mg vs 400 mg?

Within the efficacy-evaluable population of the 300-mg cohort (n = 22), the ORR and confirmed ORR were each 31.8% (95% CI, 13.9%-54.9%), with 7 patients (31.8%) achieving a partial response (PR), 13 (59.1%) with stable disease (SD), and 2 (9.1%) with PD. The DCR was 90.9% (95% CI, 70.8%-98.9%) and the median time to response (TTR) was 1.5 months.

Within the efficacy-evaluable population of the 400-mg cohort (n = 34), the ORR and confirmed ORR were 50.0% (95% CI, 32.4%-67.6%) and 47.1% (95% CI, 29.8%-64.9%), respectively. No complete responses were observed; 17 patients (50.0%) achieved a PR, 14 (41.2%) had SD, and 3 (8.8%) experienced PD. The DCR was 91.2% (95% CI, 76.3%-98.1%), and the median TTR was 1.4 months.

At the latest data cutoff of March 6, 2026, among efficacy-evaluable patients in the 400-mg cohort, the ORR reached 52.9% (n = 18) and the confirmed ORR was 50.0% (n = 17).

These responses also proved not only higher but more durable in the 400-mg cohort. As of the updated data cutoff, the median PFS was 9.6 months (95% CI, 5.3-not available).

What does ctDNA clearance reveal about treatment activity?

Biomarker analyses further supported the clinical activity of HS-10504 at the 400-mg dose, with circulating tumor DNA (ctDNA) clearance data revealing rapid and deep molecular responses across key 

Among 20 patients with NSCLC who had detectable 

mutational profiles at baseline and were evaluable for changes in mutation allele levels on treatment, marked reductions in variant allele frequency were observed in both classical 

 mutations and acquired resistance mutations after just one, 21-day cycle of treatment.

 mutations (n = 20), 95.0% (n = 19) achieved at least 50% ctDNA clearance, and 70.0% (n = 14) achieved complete ctDNA clearance. Among those with the C797S resistance mutation (n = 13), 100% of patients achieved at least 50% clearance and 84.6% (n = 11) achieved complete clearance. In patients harboring the T790M resistance mutation (n = 9), 88.9% (n = 8) achieved at least 50% clearance, and 66.7% (n = 6) achieved complete clearance.

What comes next for HS-10504 in clinical development?

“These results suggest that HS-10504 is a potential best-in-class oral option, as a new targeted therapy with a promising efficacy and safety profile, for EGFR TKI–pretreated patients with a C797S mutation. Further clinical development is ongoing,” Xie concluded.

Xie had no financial relationships to disclose.

Xie Z, Wang Q, Wu L, et al. The safety, tolerability, and efficacy of HS-10504 in patients with EGFR mutation-positive locally advanced or metastatic NSCLC: initial results from a first-in-human phase 1 study. 

. 2026;86(suppl 8):CT302. doi:10.1158/1538-7445.AM2026-CT302

A study of HS-10504 in patients with advanced or metastatic non-small-cell lung cancer(NSCLC). ClinicalTrials.gov. Updated September 17, 2025. Accessed May 5, 2026. https://clinicaltrials.gov/study/NCT06461156

HS-10504, a fourth-generation EGFR TKI selective for sensitizing EGFR mutations and C797S (±T790M), showed early clinical activity in heavily pretreated advanced EGFR-mutant NSCLC. In dose expansion, 400 mg yielded higher response rates than 300 mg (confirmed ORR ~50% vs ~32%) with rapid time to response (~1.4–1.5 months) and median PFS 9.6 months on updated follow-up. Toxicities were generally manageable, though grade ≥3 events and dose modifications were more frequent at 400 mg. ctDNA clearance supported deep molecular responses.

Phase 1 data show HS-10504 yields encouraging responses and manageable safety in EGFR C797S–mutant NSCLC post TKI therapy.

HS-10504 Shows Promising Activity in EGFR C797S–Mutant NSCLC After TKI Resistance

2026 European Society for Medical Oncology (ESMO) Breast Cancer Congress

, taking place May 6 to 8, 2026, in Berlin, Germany, 

® asked leading breast oncologists to share the presentations and conversations at the top of their lists. We gathered exclusive insights from:

Sarah Sammons, MD, associate director of the Metastatic Breast Cancer Program and a senior physician at Dana-Farber Cancer Institute, as well as an assistant professor of medicine at Harvard Medical School, both in Boston, Massachusetts

Paolo Tarantino, MD, PhD, a clinical fellow at Dana-Farber Cancer Institute

Sara M. Tolaney, MD, MPH, chief of the Division of Breast Oncology and associate director of the Susan F. Smith Center for Women’s Cancers and a senior physician at Dana-Farber Cancer Institute, as well as an associate professor of medicine at Harvard Medical School

“I always love going to Berlin for ESMO Breast, because there are always so many interesting subanalyses and updates that sometimes affect practice or at least tell us how to treat patients better and what to prioritize,” Tarantino emphasized. “ESMO Breast 2026 has several interesting oral presentations, mini-oral presentations, and posters. Among these are some I'm very curious about. I cannot wait to go to Berlin and jump into the presentations and posters. If you will be in Berlin, feel free to reach out! One of the things I love most about ESMO Breast is that it always provides a small space where people can meet, discuss, and build collaborations.”

Read on for a glance at studies you should keep an eye on, as well as how their results might propel the future of breast oncology.

What data updates in HER2-positive early-stage breast cancer are important to note?

LBA1 - Residual Cancer Burden (RCB) Following Neoadjuvant Treatment (NAT) With Trastuzumab Deruxtecan (T-DXd) Followed by Paclitaxel + Trastuzumab + Pertuzumab (THP) vs Dose-Dense Doxorubicin + Cyclophosphamide Followed by THP (ddAC-THP) in High-Risk HER2+ Early-Stage Breast Cancer (eBC)

4-4:10 PM Central CEST (Central European Summer Time)

214O - Chemotherapy-Free, Pathological Complete Response (pCR)-Guided Strategy With Trastuzumab-Pertuzumab (HP) and T-DM1 in HER2+ Early Breast Cancer (EBC): PHERGain-2

216RO - 5-Year Invasive Disease-Free Survival (iDFS) of the Strategy-Based, Randomized Phase II PHERGain Trial Evaluating Chemotherapy (CT) De-Escalation in HER2[+] Early Breast Cancer (EBC) Patients (pts)

: The [phase 3] DESTINY-Breast11 trial [NCT05113251] was a landmark study investigating the novel treatment regimen of fam-trastuzumab deruxtecan-nxki [T-DXd; Enhertu] followed by paclitaxel plus trastuzumab [Herceptin] and pertuzumab [Perjeta; THP] in HER2-positive early-stage breast cancer. We've already seen 

 showing that T-DXd followed by THP outperforms dose-dense doxorubicin and cyclophosphamide plus THP (ddAC-THP) in terms of pathologic complete response [pCR] rate.

 We'll see an update of the study regarding residual breast cancer burden [RCB] at [ESMO Breast 2026], and 

: Some of the data are covering updated analyses from prior presentations. We've seen data from DESTINY-Breast11, and we will see data that will evaluate RCB within that trial that will be interesting. We'll also see updated data from the [phase 2] PHERGain trial [NCT03161353] that investigated pre-operative trastuzumab plus pertuzumab. We'll also see data from the phase 2 PHERGain-2 trial [NCT04733118]. These 3 studies assess different perspectives of escalation of care in the preoperative setting, as well as what I would consider more de-escalation of preoperative treatment for patients with HER2-positive disease.

: PHERGain-2 is a trial testing a chemotherapy-free strategy as neoadjuvant treatment for HER2-positive breast cancer with selective trastuzumab/pertuzumab and ado-trastuzumab emtansine [Kadcyla] escalation in patients who require it, as well as the predictive ability of MRI to understand whether this can help tailor treatment in early-stage HER2-positive breast cancer. This trial is going to be extremely interesting. Then there is a subanalysis of a trial that [may change] practice: DESTINY-Breast11, which investigated T-DXd in the neoadjuvant setting, with or without sequential THP. Investigators will present the analysis of outcomes by RCB. This is intriguing and will tell us more about this regimen, which we expect may be approved over the coming months to manage early-stage HER2-positive breast cancer, [and may be] moving to other subtypes of disease, [including] the metastatic setting.

Which clinical trials will provide insights into antibody-drug conjugate sequencing in metastatic breast cancer?

422RO - A Phase 2 Study of Patritumab Deruxtecan (HER3-DXd) in Patients (pts) With Metastatic Breast Cancer (MBC)

LBA4 - Efficacy and Safety of Gacituzumab Govitecan (SG) Plus Trastuzumab in Patients With HER2+ Metastatic Breast Cancer After Prior Trastuzumab Deruxtecan (T-DXd): Results From the Phase II SATEEN Trial

: In advanced HER2-positive breast cancer, we will see [data from the phase 2] SATEEN trial [NCT06100874], presented by Dr Tarantino and colleagues from Dana-Farber, evaluating sacituzumab govitecan-hziy [Trodelvy] plus trastuzumab following [prior treatment] with T-DXd. This is one of the first prospective studies looking at the sequencing of topoisomerase inhibitor antibody-drug conjugates [ADCs] one after the other to see whether there's any efficacy [when using] one topoisomerase inhibitor after another. That will be interesting.

: We'll see data on ADC sequencing from prospective trials. To date, we've only seen retrospective data from case series, but we will see data from the SATEEN trial investigating the combination of sacituzumab govitecan and trastuzumab in patients who've previously received T-DXd for metastatic HER2-positive breast cancer. We'll also see data [from a phase 2 trial (NCT04699630)] with HER3-DXd in patients who previously received T-DXd for metastatic HER2-positive breast cancer. That will be the first set of prospective studies that I'm aware of that evaluate sequential ADC use. That's been a long-anticipated question that needed to be addressed.

: HER3-DXd is an interesting and active ADC, including in patients who have received prior T-DXd. I feel there's going to be a lot more data [with this agent]. ADC sequencing is one of the most controversial and discussed topics in breast oncology because we're starting to have several ADCs. Finally, at ESMO Breast, we will have at least some data [in this area]. We need so much more, and there are large trials ongoing, but ESMO Breast will be one of the first conferences where there are some data in this setting.

What early-phase data in triple-negative breast cancer might lead to paradigm-shifting advances?

426RO - Pumitamig in Combination With DB-1305/BNT325 as First-Line (1L) Treatment for Patients With Advanced or Metastatic Triple-Negative Breast Cancer (a/mTNBC): Efficacy and Safety From a Multicenter, Open-Label, Phase 1/2 Trial

: We will also see exciting novel combination data in the triple-negative setting with a VEGF-targeted bispecific antibody called pumitamig [BNT327/BMS986545] given with a TROP2-directed ADC. The phase 1/2 data [NCT05438329] with pumitamig plus DB-1305/BNT325 appear to show an exciting overall response and disease-control rates for first-line metastatic TNBC [triple-negative breast cancer], where we still have a long way to go to improve outcomes.

What research is evaluating the role of ovarian suppression in breast cancer?

LBA2 - A Window-of-Opportunity (WOO) Trial of Giredestrant +/- LHRH Analogue vs Anastrozole + LHRHa in Premenopausal Patients With ER+/HER2- Early breast Cancer: PREcoopERA

: I’m also looking forward to seeing data from the phase 2 PREcoopERA study [NCT05896566], which is trying to understand whether we need to use ovarian suppression when giving an oral selective estrogen receptor degrader. This has been a critical question, and it will be important to see [these results].

Harbeck N, Modi S, Pusztai L, et al. DESTINY-Breast11: neoadjuvant trastuzumab deruxtecan alone (T-DXd) or followed by paclitaxel + trastuzumab + pertuzumab (T-DXd-THP) vs SOC for high-risk HER2+ early breast cancer (eBC). 

. 2025;36(suppl 2):S302-S303. doi:10.1016/j.annonc.2025.08.720

Enhertu followed by THP supplemental biologics license application accepted in the US for patients with high-risk HER2-positive early-stage breast cancer prior to surgery. News release. Daiichi Sankyo. October 1, 2025. Accessed May 5, 2026. https://www.daiichisankyo.com/files/news/pressrelease/pdf/202510/20251001_E.pdf

Experts in a range of breast cancer subtypes highlight research data being presented at the 2026 ESMO Breast Cancer Congress.

Breast Cancer Experts Preview Abstracts to Watch at the 2026 ESMO Breast Cancer Congress

For decades, the relationship between fat and cancer has been treated as a question of quantity: eat less fat, reduce your risk of developing cancer.

, a journal of the American Association for Cancer Research, shows that for pancreatic cancer, the type of fat you consume matters more than the amount.

"It's really the type of fat that you're consuming, not just total fat content," says 

, an associate research scientist in YSM’s Department of Genetics and lead author of the study. "Depending on the type of fat that you consume, it can go completely different ways. We found that some fats promote cancer, as we would expect, while other fats are really good at suppressing cancer."

One fat in particular—oleic acid, the primary fatty acid in olive oil—may be accelerating tumor growth in ways scientists never anticipated. The result was surprising given oleic acid's reputation in medicine. "It's traditionally been considered a healthy type of fat for cardiovascular health," Ruiz says.

Pancreatic ductal adenocarcinoma (PDAC) is among the deadliest cancers. Only about 13% of patients diagnosed with PDAC survive five years. "More than 65,000 people are expected to be diagnosed with PDAC in the U.S. this year, with over 50,000 deaths,” Ruiz notes. “At the moment, effective treatment options are limited, especially for advanced disease. Therefore, prevention strategies are sorely needed to move the needle on PDAC mortality."

High-fat diets have long been associated with increased PDAC risk, but the precise biological mechanisms have not been pinned down. The new study, led by senior author 

, associate professor of genetics and of internal medicine at YSM, takes direct aim at that gap.

Muzumdar is also a member of Yale Cancer Center and the Yale Cancer Biology Institute at West Campus.

To find out the effects of each fat, Ruiz and colleagues designed a comprehensive dietary screen using 12 high-fat diets, each identical in caloric content but differing solely in fat source. The diets were modeled on real patterns of modern American fat consumption.

Ruiz says that, for decades, the research community broadly “gave mice very high levels of fat in their diet, often using a single fat source.” Most prior studies used lard-based diets at 60% fat by calories—a formulation that neither reflects what most people actually eat nor isolates the effects of specific fatty acids.

“Exactly what components of dietary fat cause cancer has remained a mystery,” Ruiz adds.

What the team found was striking. Diets rich in oleic acid—a monounsaturated fatty acid (MUFA) found in, among other foods, olive oil, high-oleic safflower oil, high-oleic sunflower oil, peanuts, and lard—significantly accelerated tumor development in mice carrying a genetic mutation that leads to illness closely mimicking human PDAC development. However, diets high in polyunsaturated fatty acids (PUFAs) suppressed it, especially omega-3 fatty acids, such as those found in fish oil.

"When we fed mice diets enriched with fish oil, we saw a 50% reduction in disease compared with mice fed a standard fat diet."

These findings prompted the team to explore ferroptosis, a form of programmed cell death triggered by lipid oxidation. When fatty acids are incorporated into pancreatic cell membranes, their chemical properties determine how vulnerable those cells are to oxidative damage. PUFAs oxidize readily, which makes cancer cells susceptible to ferroptosis and cell death. MUFAs resist oxidation, shielding cancer cells from that fate.

"Monounsaturated fats really protect the cancer cells from lipid oxidation," Ruiz explains. "Because oxidation is reduced, they're less likely to undergo ferroptosis." The effect on tumor development was direct and measurable. "When we increased the ratio of MUFAs to PUFAs in the diet, disease burden increased. Conversely, when we decreased the ratio, disease burden was reduced."

The study also found sex-based differences: The tumor-promoting effects of oleic acid were significant in male mice but largely absent in females. In contrast, dietary PUFAs suppressed cancer development in both sexes. Ruiz notes that these findings contribute to a growing recognition that sex can influence metabolic regulation of tumor development and highlight the need for further study in this area.

Though the study has not been replicated in humans, the clinical implications could be most immediate for high-risk groups: people with chronic pancreatitis, a family history of pancreatic cancer, late-onset diabetes, or obesity.

"One of the most common questions clinicians get is ‘What can I change in my diet to prevent cancer?’" Ruiz says. "Right now, we don’t have clear answers, but this study begins to shed light on how we might address that question."

Ruiz says the next step is determining whether dietary fat composition can improve outcomes in patients with established tumors and whether the ratio of MUFAs to PUFAs in blood could serve as an early biomarker for pancreatic cancer risk.

Pancreatic ductal adenocarcinoma risk appears to be driven more by dietary fat composition than total fat intake. In genetically engineered PDAC-prone mice, oleic acid–enriched diets accelerated tumorigenesis, whereas PUFA-rich diets, particularly omega-3 fish oil, suppressed disease by roughly 50% versus standard-fat controls. Mechanistically, membrane fatty-acid composition altered susceptibility to lipid peroxidation and ferroptosis: PUFAs promoted oxidative damage and ferroptotic cell death, while MUFAs conferred resistance. Oleic acid effects were male-specific, underscoring sex-dependent metabolic regulation and potential prevention-focused translational avenues.

Research from Yale Cancer Center showed that the type of fat consumed may matter more than amount in pancreatic cancer.

The Type of Fat—Not the Amount—Fuels Pancreatic Cancer

The phospholipid-drug conjugate radiotherapeutic Iopofosine I 131 (CLR 131) exhibited strong efficacy data, including durable responses, in patients with relapsed or refractory Waldenström macroglobulinemia, according to a report of long-term follow-up data from the phase 2b CLOVER WaM trial (NCT02952508) that was requested by the FDA .

Data showed that patients in the per-protocol population (n =55) achieved a major response rate (MRR) of 61.8% and an overall response rate (ORR) of 83.6%. Patients also experienced a median duration of response (DOR) of 17.8 months in addition to a 13.5-month median progression-free survival (PFS). These data met both primary and secondary end points for the trial and support the filing of an NDA seeking accelerated approval from the FDA. Notably, the FDA also granted 

breakthrough therapy designation to Iopofosine I 131 for this indication in June 2025

Moreover, in patients with Waldenström macroglobulinemia who had either received prior BTK inhibition (n = 39) or were refractory to BTK inhibitors (n = 33), the respective MRRs were 64.1% and 63.6%. The median DOR was 18.2 months in both subgroups, and the median PFS values were 15.9 months and 14.8 months, respectively.

“The depth, durability, and consistency of responses observed across both the total population and BTK inhibitor–treated subsets underscore iopofosine I 131’s potential as a meaningful new treatment option in Waldenström macroglobulinemia and differentiate it from currently available therapies,” Jarrod Longcor, chief operating officer of Cellectar Biosciences, stated in a news release. “With the completion of at least 12-month follow-up on all patients, we believe this dataset meets key regulatory expectations for an accelerated approval submission and positions us well as we advance toward initiating our confirmatory study.”

The open-label, multicenter trial enrolled patients who were at least 18 years of age with histologically or cytologically confirmed Waldenström macroglobulinemia.

Patients also needed to have an ECOG performance status of 2 or lower, a life expectancy higher than 6 months, and received at least 2 prior lines of therapy for Waldenström macroglobulinemia.

If patients had ongoing grade 2 or higher adverse effects (AEs) from prior treatments, malignancies in addition to Waldenström macroglobulinemia, or received total- or hemi-body irradiation prior to enrollment, they were not included in the trial.

Iopofosine I 131 in Waldenström macroglobulinemia: CLOVER-WaM Highlights

Patients in the per-protocol population achieved an MRR of 61.8% in addition to an ORR of 83.6% and a median DoR of 17.8 months.

The MRRs for patients who had previously been exposed to BTK inhibitors or were refractory to BTK inhibitors were 64.1% and 63.6%, respectively.

Iopofosine I 131 demonstrated a manageable and predictable safety profile.

Patients received a fixed-dose regimen of 4 approximately 30-minute infusions of iopofosine I 131.

MRR served as the trial’s primary end point, whereas DOR, ORR, and clinical benefit rate served as as secondary end points.

Baseline characteristics revealed that patients had received a median of 4 prior lines of therapy (range, 2-15).

 Among patients who had received prior BTK inhibition, 77% had refractory disease compared with 60% of those who had received prior chemotherapy and 58% of those who were previously exposed to both BTK inhibitors and rituximab (Rituxan).

What additional updated data have been reported with iopofosine I 131 in CLOVER WaM?

Patients in the per-protocol population achieved a very good partial response or complete response rate of 14.5% and a disease control rate of 98.2%.

Regarding safety, iopofosine I 131 demonstrated a predictable and manageable safety profile, with rates of bleeding AEs and infections both occurring in less than 10% of patients. Cytopenias were reported as the most common treatment-emergent AEs, and the nonhematologic AEs were primarily grade 2 or less.

“These mature 12-month follow-up data, as required by the FDA, further strengthen the compelling clinical profile of iopofosine I 131,” James Caruso, president and chief executive officer of Cellectar Biosciences, concluded in the news release. “Importantly, the durability of response continues to improve over time, and the consistency of activity in post–BTK inhibitor patients reinforces the potential of iopofosine I 131 to address a critical unmet need in the second-line setting and beyond. We remain committed to providing iopofosine I 131 to the thousands of patients who can benefit from treatment and plan to initiate our confirmatory study.”

Cellectar Biosciences reports positive 12-month follow-up data from phase 2b Clover WaM study demonstrating durable responses and efficacy of iopofosine I 131 in r/r Waldenström macroglobulinemia. News Release. GlobeNewswire. May 5, 2026. Accessed May 5, 2026. https://www.cellectar.com/investors/news-events/press-releases/detail/390/cellectar-biosciences-reports-positive-12-month-follow-up-data-from-phase-2b-clover-wam-study-demonstrating-durable-responses-and-efficacy-of-iopofosine-i-131-in-rr-waldenstrm-macroglobulinemia

Cellectar granted U.S. FDA breakthrough therapy designation for iopofosine I 131 in Waldenstrom macroglobulinemia (WM). News release. Cellectar Biosciences. June 4, 2025. Accessed May 5, 2026. https://www.cellectar.com/news-media/press-releases/detail/359/cellectar-granted-u-s-fda-breakthrough-therapy-designation

Study of Iopofosine I-131 (CLR 131) in select B-cell malignancies (CLOVER-1) with expansion in Waldenstrom (CLOVER-WaM). ClinicalTrials.gov. Updated March 18, 2026. Accessed May 5, 2026. https://clinicaltrials.gov/study/NCT02952508

Iopofosine I-131 (CLR 131), a phospholipid-drug conjugate radiotherapeutic, produced durable activity in relapsed/refractory Waldenström macroglobulinemia with 12-month FDA-requested follow-up. In the per-protocol cohort (n=55), major response rate was 61.8% and overall response rate 83.6%, with median duration of response 17.8 months and median PFS 13.5 months. Responses were consistent after prior or refractory BTK inhibition (MRR ~64%; DOR 18.2 months; PFS ~15 months). Toxicity was largely predictable, dominated by cytopenias, with low bleeding and infection rates.

Iopofosine I 131 produced strong responses in Waldenström macroglobulinemia, according to 12-month folllow-up data from CLOVER WaM requested by the FDA.

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