Caroline Seymour

Verzenio showed meaningful improvement for some patients with HR-positive, HER2-negative breast cancer after prior CDK4/6 treatment: © stock.adobe.com.

Data from the retrospective rAMBER study, presented at the 

2025 San Antonio Breast Cancer Symposium(SABCS),

 showed that Verzenio (abemaciclib) monotherapy offered clinical benefit to some patients with hormone receptor (HR)–positive, HER2-negative breast cancer who had progressed on prior CDK4/6 inhibitor therapy.

The study evaluated how effective Verzenio could be when used alone after progression on previous CDK4/6 therapy, offering insight into the potential of sequential treatment in this patient population.

Approximately 33% of patients who received Verzenio across four academic centers (30 patients) derived meaningful clinical benefit from the therapy. Verzenio was generally well tolerated for more than 180 days, even in patients whose disease had progressed on prior Ibrance therapy and ongoing endocrine treatments. Most patients (23 of 30) continued on Verzenio until either disease progression or death, while the remaining 7 patients discontinued therapy due to side effects.

The median duration of treatment with Verzenio was 4 months following progression on Ibrance-based therapy, and the median number of intervening lines of therapy between Ibrance and Verzenio was 2, highlighting the potential of Verzenio to offer disease control even after multiple prior treatments.

“CDK4/6 inhibitors have become the standard of care for patients with advanced HR-positive, HER2-negative breast cancer. However, uncertainty remains regarding the efficacy of re-introducing CDK4/6 inhibitors after disease progression on prior therapy,” said Dr. Sahar Shahamatdar, an internal medicine resident at Massachusetts General Hospital, and her coauthors. “rAMBER is the first study to evaluate the effectiveness of Verzenio monotherapy in this setting, offering new insights into sequential CDK4/6 therapy and potential treatment strategies for patients who have exhausted standard options.”

Verzenio was approved by the U.S. Food and Drug Administration (FDA) in February 2018

 for use in combination with an aromatase inhibitor as a frontline therapy for postmenopausal women with HR-positive, HER2-negative advanced or metastatic breast cancer. This decision was supported by prior phase 3 MONARCH 3 data showing a median progression-free survival of 28.2 months with Verzenio versus 14.8 months for patients receiving placebo, confirming its efficacy in first-line settings.

The rAMBER study collected retrospective patient data from Massachusetts General Hospital, Barnes-Jewish Hospital, University of Pittsburgh Medical Center, and Moffitt Cancer Center. Patients with metastatic HR-positive, HER2-negative breast cancer who received Verzenio monotherapy after disease progression on a CDK4/6 inhibitor–based regimen were included. Patients were divided into two subgroups: sequential CDK4/6 therapy (6 patients) and nonsequential therapy (24 patients). Data were collected under Institutional Review Board–approved protocols, examining patient demographics, clinical outcomes, and treatment duration. Serial RECIST measurements were collected from imaging studies, and solid tumor and cell-free DNA were analyzed using targeted sequencing.

Each biopsy was assigned a phenotype based on the best clinical response and duration of response relative to biopsy timing, defined as sensitive, acquired resistant, or intrinsically resistant. One patient achieved a partial response with Verzenio, seven patients experienced stable disease, and eight experienced disease progression. Genomic analysis of 23 biopsies showed RB1 alterations were associated with acquired or intrinsic resistance, and ESR1 alterations were found across all biopsy phenotypes.

“Preliminary genetic analyses revealed enrichment in RB1 alterations in patients with rapid disease progression,” Shahamatdar and her coauthors concluded. These findings highlight the potential of Verzenio monotherapy to provide clinical benefit even after prior CDK4/6 inhibitor therapy and demonstrate the importance of understanding tumor genetics when considering sequential treatment strategies for advanced breast cancer.

“Updated analyses from the retrospective rAMBER study exploring abemaciclib after prior CDK4/6 inhibitor progression in metastatic hormone-receptor positive breast cancer,” by Dr. Sahar Shahamatdar, et al. Presented at: San Antonio Breast Cancer Symposium; December 9-12, 2025; San Antonio, TX. Abstract PS1-10-01.

“FDA approves abemaciclib as initial therapy for HR-positive, HER2-negative metastatic breast cancer,” by the U.S. FDA. News release; Feb. 26, 2018.

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Verzenio (abemaciclib) monotherapy has shown clinical benefits for some patients with hormone receptor-positive, HER2-negative breast cancer who progressed on prior CDK4/6 inhibitor therapy, according to the rAMBER study. Approximately 33% of patients experienced meaningful benefits, with Verzenio generally well tolerated. The study highlights Verzenio's potential for disease control after multiple treatments. Genomic analysis revealed RB1 and ESR1 alterations linked to resistance. These findings underscore the importance of understanding tumor genetics in developing sequential treatment strategies for advanced breast cancer.

Verzenio showed meaningful improvement for some patients with HR-positive, HER2-negative breast cancer after prior CDK4/6 treatment.

Verzenio Offers Potential Benefit After Prior Therapy in HR+/HER2– Breast Cancer

Tukysa added to Herceptin and Perjeta improved progression-free survival versus placebo in HER2-positive metastatic breast cancer after initial therapy.

Tukysa (tucatinib) combined with Herceptin (trastuzumab) and Perjeta (pertuzumab) extended progression-free survival as a frontline maintenance approach compared with placebo plus Herceptin and Perjeta in patients with HER2-positive metastatic breast cancer whose disease had not progressed after docetaxel with Herceptin and Perjeta, according to findings presented at the 

2025 San Antonio Breast Cancer Symposium (SABCS).

Topline results from the phase 3 HER2CLIMB-05 trial were first announced in October 2025, indicating that the study met its primary end point. A preliminary look at the data, with median follow-up of approximately 23 months, showed that the median PFS was 24.9 months with tucatinib/HP (326 patients) versus 16.3 months with placebo/HP (328 patients).

The PFS benefit with tucatinib extended across all prespecified patient subgroups, including diagnosis (de novo or recurrent), hormone receptor (HR) status (negative or positive), brain metastases at baseline (yes or no), prior anti-HER2 therapy (yes or no), best response to THP induction (complete response/partial response or stable disease/non-CR/PR), disease type (visceral or nonvisceral), ECOG performance status (0 or 1), region (North America, Europe, Asia Pacific, or rest of the world), age (under 65 or aged 65 years and older), and race (White, Asian, or other).

“HER2CLIMB-05 has demonstrated that the addition of tucatinib to HP represents an enhanced frontline maintenance therapy option for patients with HER2-positive metastatic breast cancer, providing an opportunity to prolong time to disease progression and time off chemotherapy,” Dr. Erika Hamilton, lead study author and director of breast cancer research at Sarah Cannon Research Institute in Nashville, Tennessee, said during the meeting.

What were the key elements of the HER2CLIMB-05 trial?

First-line treatment for patients with HER2-positive metastatic breast cancer typically includes taxane-based chemotherapy with HP, followed by HP maintenance, but disease progression often prevents patients from reaching second-line therapy. Prior data from the pivotal HER2CLIMB trial showed that adding tucatinib to capecitabine and trastuzumab improved PFS and overall survival (OS) even in heavily pretreated populations, including patients with brain metastases. HER2CLIMB-05 evaluated whether incorporating tucatinib into first-line maintenance with HP could further improve outcomes by intensifying both extracellular and intracellular HER2 targeting.

HER2CLIMB-05 is a randomized, double-blind, placebo-controlled, international trial that enrolled patients with centrally confirmed HER2-positive metastatic breast cancer with no evidence of progression after 4 to 8 cycles of THP, no or asymptomatic brain metastases confirmed by contrast-enhanced MRI at screening, and an ECOG performance status of 0 or 1.

Patients were randomly assigned 1:1 to 300 mg of oral tucatinib twice daily (326 patients) or matched placebo (328 patients), both in combination with HP every 21 days with or without endocrine therapy. Trastuzumab was administered intravenously at 6 mg/kg or 600 mg subcutaneously and pertuzumab at 420 mg IV. The fixed-dose SC combination of 600 mg trastuzumab, 600 mg pertuzumab, and 20,000 units of hyaluronidase-zzxf (Phesgo) was also allowed.

Therapy continued until unacceptable toxicity, disease progression, consent withdrawal, or study closure. Crossover was prohibited.

The primary end point was investigator-assessed PFS per RECIST 1.1 criteria. Secondary end points included OS, PFS per blinded independent central review, central nervous system PFS, safety, health-related quality of life, and pharmacokinetics. Patients were stratified by diagnosis, hormone receptor status, and presence or history of brain metastases.

How did the regimen perform according to hormone receptor status and was an OS benefit seen?

With respect to PFS by hormone receptor status, greater benefit was seen in the hormone receptor–negative population, although benefit was also present in the hormone receptor–positive population. In the hormone receptor–negative cohort, median PFS was 24.9 months with tucatinib versus 12.6 months with placebo. In the hormone receptor–positive cohort, median PFS was 25.0 months with tucatinib versus 18.1 months with placebo. Assessment of OS showed a numerical trend for improvement with tucatinib.

What was the safety profile of the regimen?

“The tucatinib and HP combination showed a manageable safety profile, with diarrhea, nausea, and elevated liver enzymes, mostly low grade, being the most common side effects,” Hamilton reported. Treatment-emergent side effects occurred in 99.1% of patients receiving tucatinib and 96.6% of those receiving placebo. Grade 3 or greater side effects, serious side effects, and side effects leading to death occurred in 43.2%, 16.9%, and 0.3% of tucatinib patients, respectively, and in 24.4%, 8.0%, and 0.3% of placebo patients.

Side effects led to treatment discontinuation in 13.8% of tucatinib patients versus 4.6% of placebo patients. The most common side effects prompting discontinuation were hepatic events (7.7% tucatinib, 0% placebo) and diarrhea (1.5% tucatinib, 0.9% placebo). Dose modifications due to side effects were required in 55.8% of tucatinib patients and 34.6% of placebo patients.

“HER2CLIMB-05: A randomized, double-blind, phase 3 study of tucatinib versus placebo in combination with trastuzumab and pertuzumab as maintenance therapy for HER2+ metastatic breast cancer,” Dr. Erika Hamilton. Presented at: 2025 San Antonio Breast Cancer Symposium; December 9-12, 2025; San Antonio, TX. Abstract GS1-01.

“Tukysa combination significantly improves progression-free survival as first-line maintenance in HER2+ metastatic breast cancer in HER2CLIMB-05 trial,” Pfizer. News release; Oct. 14, 2025. Accessed December 10, 2025.

The combination of tucatinib with trastuzumab and pertuzumab significantly extended progression-free survival (PFS) in HER2-positive metastatic breast cancer patients as a frontline maintenance therapy. The HER2CLIMB-05 trial demonstrated a median PFS of 24.9 months with tucatinib versus 16.3 months with placebo. The PFS benefit was consistent across various patient subgroups, including hormone receptor status and brain metastases. Tucatinib showed a manageable safety profile, with common side effects being diarrhea, nausea, and elevated liver enzymes. The trial highlighted tucatinib's potential to enhance maintenance therapy in this patient population.

Tukysa Combo Boosts Frontline Maintenance in Advanced HER2+ Breast Cancer

Lenvima and Keytruda with chemo did not help patients with metastatic esophageal squamous cell carcinoma live longer than Keytruda and chemotherapy alone.

The combination of Lenvima (lenvatinib) and Keytruda (pembrolizumab) with chemotherapy did not help patients with metastatic esophageal squamous cell carcinoma live longer compared with Keytruda and chemotherapy alone, according to results from a phase 3 study presented at the 2025 ESMO Congress.

The median OS in the Lenvima arm was 17.6 months versus 15.5 months in the chemoimmunotherapy arm. The 12- and 24-month OS rates were 65% and 34% in the investigational arm versus 61% and 32% in the control arm.

In patients with a PD-L1 combined positive score (CPS) of at least 10, the median OS was 18 months in the Lenvima arm versus 15.8 months in the control arm. The 12- and 24-month OS rates were 67% and 36% in the investigational arm versus 63% and 31% in the control arm.

“Lenvatinib plus pembrolizumab and chemotherapy did not significantly improve OS as first-line treatment for patients with metastatic ESCC versus pembrolizumab plus chemotherapy,” lead study author Dr. Jong-Mu Sun, of the Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine in Seoul, Republic of Korea, stated during the presentation.

Overall survival (OS): time from treatment start or diagnosis until death from any cause.

Progression-free survival (PFS): time during and after treatment that a patient lives without cancer growing or spreading.

Duration of response (DOR): length of time a treatment keeps cancer under control after it first responds.

Overall response rate (ORR): percentage of patients whose cancer shrinks or disappears after treatment.

What Are the Key Components of the Trial?

The trial enrolled patients at least 18 years of age with histologically or cytologically confirmed locally advanced, unresectable, or metastatic ESCC. Prior treatment, an ECOG performance status of 2 or higher, and lack of measurable disease per RECIST 1.1 criteria excluded patients from enrollment.

A total of approximately 850 patients were randomly assigned 1:1 to treatment. In the investigational arm, patients received 8 milligrams of oral Lenvima once daily plus 400 milligrams of intravenous (IV) Keytruda every six weeks and either cisplatin plus 5-fluorouracil (FP) or paclitaxel plus cisplatin (TP) every three weeks, or modified FOLFOX6 every two weeks. This was followed by 20 milligrams of Lenvima plus 400 milligrams of Keytruda every six weeks until progression, unacceptable side effects, or withdrawal. In the control arm, patients received 400 milligrams of IV Keytruda every six weeks plus FP or TP every three weeks or modified FOLFOX6 every two weeks in accordance with local standards.

OS served as the primary end point. Secondary end points included progression-free survival (PFS), overall response rate (ORR), duration of response (DOR) by blinded independent central review, and safety.

A total of 850 patients were randomly assigned to the investigational (423 patients) and control (427 patients) arms: 421 and 426 of whom were treated in the respective arms. In the investigational arm, 2 patients completed treatment and 93 patients remained on therapy. Reasons for discontinuation included progressive disease (206 patients), side effects (72 patients), clinical progression (25 patients), patient decision (18 patients), physician decision (3 patients), and protocol violation (2 patients). In the control arm, 23 patients completed treatment and 70 patients remained on therapy. Reasons for discontinuation included progressive disease (202 patients), side effects (73 patients), clinical progression (22 patients), patient decision (25 patients), physician decision (10 patients), and follow-up loss (1 patient).

Baseline characteristics were well balanced between treatment groups, Sun said. Within the investigational arm, the median age was 64; 49% were above 65. Most patients were male (78%), Asian (66%), and from East Asia (66%). ECOG performance status was 1 in 64% of cases, and most patients had a PD-L1 CPS of 10 or greater (66%). Ninety-nine percent of patients did not have brain metastases and had stage 4B disease. The preferred choice of chemotherapy was modified FOLFOX6 (65%), followed by FP (24%) and TP (10%).

Per the study design, efficacy was evaluated in all randomized patients, whereas safety was limited to all randomized patients who received at least one dose of study therapy. PFS and ORR were not tested for statistical significance since OS was not positive. The data cutoff for this analysis was May 8, 2025, at which point approximately 482 OS events had occurred, or 42 months had passed since the first participant had been randomized.

What Additional Efficacy Data Were Presented?

Sun stated that the OS results were consistent across prespecified subgroups, including PD-L1 status (CPS greater or equal to 10 versus CPS less than 10), region (East Asia versus North America and Western Europe versus rest of the world), and chemotherapy (FP versus TP versus modified FOLFOX).

Additional results indicated that the median PFS in all randomized patients was 7.2 months in the Lenvima arm versus 6.9 months in the control arm. The 12- and 24-month PFS rates were 31% and 12% in the investigational arm versus 23% and 15% in the control arm.

The median PFS in patients with a PD-L1 CPS of at least 10 was 8.1 months in the Lenvima arm versus 6.9 months in the control arm. The 12- and 24-month PFS rates were 36% and 16% in the investigational arm versus 25% and 14% in the control arm.

The ORR was 62.2% in the Lenvima arm versus 54.8% in the chemoimmunotherapy arm. In the Lenvima arm, best responses included complete response (16.3%), stable disease (22%), and progressive disease (8%); 7.3% of patients were not evaluable. In the control arm, best responses included complete response (19.2%), partial response (35.6%), stable disease (29.7%), and progressive disease (8.9%); 5.4% of patients were not evaluable.

The median DOR was 8.1 months in the Lenvima arm and 17% of patients experienced a response lasting 24 months or longer. In the control arm, the median DOR was 6.8 months and 21% of patients experienced a response lasting at least 24 months.

What Were the Key Safety Data That Were Presented?

The median duration of treatment exposure was 7.1 months in the Lenvima arm versus 5.6 months in the control arm. In the investigational arm, any-grade side effects occurred in 99.5% of patients (grade 3 [severe] or higher, 81.2%; grade 5 [death], 9.7%). Side effects leading to drug discontinuation occurred in 33.3% of patients. Treatment-related side effects occurred in 97.1% of patients.

In the control arm, any-grade side effects occurred in 99.3% of patients (grade 3 or higher, 79.1%; grade 5, 11.5%). Side effects leading to drug discontinuation occurred in 39% of patients. Treatment-related side effects occurred in 96.5% of patients.

Side effects that occurred in at least 15% of patients in either arm in order of frequency were decreased neutrophil count, nausea, hypertension, diarrhea, decreased platelet count, anemia, hypothyroidism, stomatitis, decreased white blood cell count, fatigue, decreased appetite, palmar plantar erythrodysesthesia syndrome, proteinuria, aspartate aminotransferase increase, vomiting, rash, weight decrease, constipation, alanine aminotransferase increase, pyrexia, increased lipase, increased amylase, peripheral neuropathy, hypoalbuminemia, and pneumonia.

Immune-mediated side effects and infusion reactions in the experimental arm included adrenal insufficiency, colitis, encephalitis, gastritis, hepatitis, hyperthyroidism, hypophysitis, hypothyroidism, infusion reactions, myocarditis, myositis, nephritis, pancreatitis, pneumonitis, severe skin reactions, thyroiditis, type 1 diabetes mellitus, and vasculitis.

“Safety profiles were generally consistent with the known safety profiles of Lenvima in combination with Keytruda and chemotherapy or the Keytruda plus chemotherapy regimen,” Sun concluded.

“Lenvatinib Plus Pembrolizumab and Chemotherapy Versus Pembrolizumab and Chemotherapy in Untreated Metastatic Esophageal Squamous Cell Carcinoma” by Dr. Jong-Mu Sun, et al., ESMO Congress 2025.

“Efficacy and Safety of Pembrolizumab Plus Lenvatinib Plus Chemotherapy in Participants With Metastatic Esophageal Carcinoma” by Dr. Jong-Mu Sun, et al., ClinicalTrials.gov.

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The combination of Lenvima (lenvatinib) and Keytruda (pembrolizumab) with chemotherapy did not significantly improve overall survival (OS) in patients with metastatic esophageal squamous cell carcinoma (ESCC) compared to Keytruda and chemotherapy alone. The median OS was slightly higher in the Lenvima arm, but not statistically significant. Progression-free survival (PFS) and overall response rate (ORR) showed modest improvements. Safety profiles were consistent with known data, with high rates of side effects in both treatment arms. The study involved 850 patients, with balanced baseline characteristics.

Lenvima Combo Fails to Extend Survival in Esophageal Cancer

For patients with relapsed/refractory mantle cell lymphoma Lunsumio plus Polivy was associated with durable responses. Image generated by Google Gemini.

Among patients with relapsed/refractory mantle cell lymphoma (MCL) with prior exposure to BTK inhibition, treatment with Lunsumio (mosunetuzumab-axgb) plus Polivy (polatuzumab vedotin-piiq) was associated with durable responses and was found to be well tolerated, clinical trial results have shown.

Findings from an MCL dose-expansion cohort of a phase 2 trial were presented at the 2025 SOHO Annual Meeting.

Among all treated patients (42 patients), the overall response rate (ORR) was 88%; the complete response (CR) and partial response (PR) rates were 79% and 9%, respectively. The efficacy of this combination was observed across high-risk patient subgroups, including those at least 70 years of age (18 patients; ORR, 83%; CR rate, 78%; PR rate, 5%), those who had received prior CAR-T cell therapy (11 patients; 91%; 82%; 9%), those with a Ki-67 score of at least 50% (28 patients; 93%; 79%; 14%), those with pleomorphic or blastoid MCL (16 patients; 94%; 69%; 25%), and those with TP53 mutations or deletions (13 patients; 100%; 92%; 8%).

Overall response rate: patients who responded partially or completely to treatment.

Progression-free survival: the time a patient lives without their disease spreading or worsening.

Overall survival: the time a patient lives, regardless of disease status.

“[Lunsumio] and [Polivy], in my opinion, is going to be a good off-the-shelf option for relapsed/refractory MCL before or after CAR T-cell therapy,” lead study author Dr. Michael L. Wang, said in the presentation.

Wang is a professor in the Department of Lymphoma/Myeloma and the Department of Stem Cell Transplantation in the Division of Cancer Medicine at The University of Texas MD Anderson Cancer Center in Houston.

What Was the Rationale for Investigating Lunsumio in Combination With Polivy in Patients With MCL?

Lunsumio is a CD20xCD3-directed, T-cell engaging bispecific antibody. Polivy is a CD79-directed antibody-drug conjugate.

“The two are complementary in their mechanisms of action,” Wang noted. “They were synergistic in preclinical studies.”

Previous findings from the dose-expansion large B-cell lymphoma (LBCL) cohort (98 patients) of the phase 2 study showed that at a median follow-up of 23.9 months, Lunsumio plus Polivy elicited an ORR of 59.2% and a CR rate of 45.9%. Furthermore, the median duration of CR was not reached.

What Was the Design of the MCL Portion of the Phase 2 Study of Lunsumio Plus Polivy in Relapsed/Refractory MCL?

This phase 2 study is investigating the efficacy, safety, pharmacokinetics and pharmacodynamics of Lunsumio plus Polivy in patients with B-cell non-Hodgkin lymphoma, including LBCL, follicular lymphoma and MCL.

Patients received the investigational combination in a fixed-duration treatment approach that included Lunsumio administered subcutaneously at 45 mg in 21-day cycles (5-mg step-up dosing occurred in cycle 1) for a total of 17 cycles; and intravenous Polivy administered at 1.8 mg/kg on day 1 of cycles 1 through 6. Hospitalization was not required. Patients received corticosteroid premedication before each dose in cycle 1.

What Were the Baseline Characteristics of Patients Included in the Trial?

Patients had a median age of 68 years and had received three prior lines of therapy. Prior therapies included BTK inhibition (100%), CAR T-cell therapy (26%) and autologous stem cell transplant (31%). In total, 93% of patients were refractory to their last prior therapy. TP53 mutations or deletions were present in 39% of patients, 38% of patients had blastoid or pleomorphic disease, and 43% of patients had bone marrow involvement. Ki-67 scores of at least 30% and at least 50% were reported in 76% and 67% of patients, respectively. Additionally, 48% of patients had a simplified International Prognostic Index for MCL score of at least 6. Overall, 71% of patients had at least three high-risk features.

“This is a high-risk, heavily treated population,” Wang contextualized.

What Additional Efficacy Data Were Observed With Lunsumio Plus Polivy?

The responses observed with this combination were early and durable, Wang noted. At a median follow-up of 15.9 months, among all responders (37 patients), the median time to first response was 2.7 months, the median DOR was not reached and the 12-month response rate was 66%. Among complete responders (33 patients), the median time to first CR was 2.8 months, the median duration of CR was not reached and the 12-month response rate was 71.9%.

Among all treated patients, the median progression-free survival (PFS) was 18.6 months, and the 12-month PFS rate was 74.8%. The median overall survival (OS) was 20.7 months and the 12-month OS rate was 83.1%.

What Was the Safety Profile of Lunsumio Plus Polivy in Patients With MCL?

All patients experienced side effects, and 93% of patients experienced treatment-related side effects. The rates of grade 3 (severe)/4 (life-threatening) side effects and treatment-related side effects were 69% and 60%, respectively. Serious side effects and treatment-related side effects were reported in 62% and 41% of patients, respectively. Grade 5 (fatal) side effects and treatment-related side effects occurred in 12% and 2% of patients, respectively; these included COVID-19 pneumonia (three patients), pneumonia (one patient) and West Nile virus encephalitis (one patient). Treatment discontinuation related to side effects and treatment-related side effects occurred in 24% and 12% of patients, respectively. Patients received a median of 15 Lunsumio cycles and six Polivy cycles.

Side effects and treatment-related side effects that occurred in at least 20% of patients included fatigue, injection site reaction, neutropenia/decreased neutrophil counts, diarrhea, cytokine release syndrome (CRS), nausea, dyspnea, constipation, cough, headache, pyrexia, thrombocytopenia/decreased platelet counts, COVID-19 and myalgia. Side effects of interest included injection site reaction (grade 1 (mild), 52%; grade 2 (moderate), 5%), peripheral neuropathy (grade 1, 29%; grade 2, 12%), immune effector cell–associated neurotoxicity syndrome (grade 2, 2%), infections (any grade, 71%; grade 3/4, 14%; grade 5, 12%), tumor flare (grade 1, 5%; grade 2, 7%), neutropenia/decreased neutrophil counts (any grade, 45%; grade 3/4, 41%), and febrile neutropenia (grade 3, 5%).

Notably, B-cell depletion occurred rapidly during treatment, and investigators observed recovery of B-cell counts following treatment.

Wang ML, Kamdar M, Assouline S, et al. Fixed-duration outpatient subcutaneous mosunetuzumab + polatuzumab vedotin shows robust efficacy in a phase II study of relapsed/refractory post-BTKi mantle cell lymphoma. Presented at: 2025 SOHO Annual Meeting. September 3-6, 2025; Houston, TX. Abstract MCL-1493.

Budde LE, Olszewski AJ, Assouline S, et al. Mosunetuzumab with polatuzumab vedotin in relapsed or refractory aggressive large B cell lymphoma: a phase 1b/2 trial. 

. 2024;30(1):229-239. doi:10.1038/s41591-023-02726-5

A study to evaluate the safety and efficacy of mosunetuzumab (BTCT4465A) in combination with polatuzumab vedotin in B-cell non-Hodgkin lymphoma. ClinicalTrials.gov. Updated November 29, 2024. Accessed September 6, 2025. https://www.clinicaltrials.gov/study/NCT03671018

Lunsumio (mosunetuzumab-axgb) combined with Polivy (polatuzumab vedotin-piiq) demonstrated significant efficacy and tolerability in patients with relapsed/refractory mantle cell lymphoma (MCL) previously treated with BTK inhibitors. The phase 2 trial showed an overall response rate of 88%, with complete and partial response rates of 79% and 9%, respectively. The combination was effective across high-risk subgroups, including those with prior CAR-T therapy and TP53 mutations. Despite a high incidence of side effects, the treatment was generally well-tolerated, with manageable safety profiles and durable responses.

For patients with relapsed/refractory mantle cell lymphoma Lunsumio plus Polivy was associated with durable responses.

Caroline Seymour

Verzenio Offers Potential Benefit After Prior Therapy in HR+/HER2– Breast Cancer

Tukysa Combo Boosts Frontline Maintenance in Advanced HER2+ Breast Cancer

Lenvima Combo Fails to Extend Survival in Esophageal Cancer

Lunsumio plus Polivy Associated With Responses in MCL

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