cevostamab (RG6160) / Roche - LARVOL DELTA

Phase 2 study of cevostamab consolidation following BCMA CAR T cell therapy: preliminary safety, efficacy, and correlative data from the "STEM" (Sequential T Cell-Engagement for Myeloma) trial (ASH 2025) - P2 | "Median number of prior lines was 4 (2-10), with 74% triple-class refractory, 11% prior BCMA therapy, and 11% prior talquetamab. Twenty-five (93%) received cilta-cel and 2 (7%) ide-cel... To date, cevostamab consolidation starting 10-12 weeks post-CAR T cell infusion at 3.6mgsingle step-up and 132mg q3wk target dose appears feasible and well-tolerated in heavily-pretreatedRRMM, with low rates of non-hematologic G3/4 TEAE's, including infections. Preliminary efficacy appearspromising, with over 90% showing sustained MRD-negative CR at 1 year. Analyses and follow-up areongoing."

CAR T-Cell Therapy • Clinical • IO biomarker • P2 data • Ataxia • Autoimmune Hepatitis • Cough • Gastroenterology • Gastrointestinal Disorder • Hepatology • Immunology • Infectious Disease • Movement Disorders • Multiple Myeloma • Musculoskeletal Pain • Neutropenia • Respiratory Diseases • Thrombocytopenia

Subcutaneous cevostamab demonstrates manageable safety and clinically meaningful activity in Relapsed/Refractory multiple myeloma (RRMM): First results from the Phase Ib CAMMA 3 study (ASH 2025) - "CRS primarily occurred in C1 and was mostly low Gr (Gr 1: 34.5%; Gr 2: 32.8%; Gr 3: 1.7%).Patients with CRS were frequently managed with tocilizumab (50.0%), steroids (67.5%), or both agents(32.5%); all events resolved. SC cevostamab monotherapy induces deep and durable responses and has manageablesafety in patients with late-line RRMM, many of whom had received prior BCMA-targeted therapies.Efficacy and safety (including CRS) appear generally comparable with that observed with IV cevostamabmonotherapy in patients with late-line RRMM, with the exception of the occurrence of low Gr ISRs."

Clinical • IO biomarker • P1 data • CNS Disorders • Dermatology • Hematological Disorders • Hematological Malignancies • Infectious Disease • Multiple Myeloma • Neutropenia • Pruritus • Thrombocytopenia

GO39775: Dose-Escalation Study of Cevostamab in Participants With Relapsed or Refractory Multiple Myeloma (R/R MM) (clinicaltrials.gov) - P1 | N=355 | Completed | Sponsor: Genentech, Inc. | Active, not recruiting ➔ Completed | Trial completion date: Apr 2026 ➔ Jan 2026 | Trial primary completion date: Apr 2026 ➔ Jan 2026

Trial completion • Trial completion date • Trial primary completion date • Hematological Malignancies • Multiple Myeloma • Oncology

Phase 2 Study of Cevostamab Consolidation Following BCMA CAR T Cell Therapy: Preliminary Safety and Efficacy Data from the "STEM" (Sequential T Cell-Engagement for Myeloma) Trial (IMS 2025) - P2 | "RRMM pts who received standard of care CAR T cells (ide-cel or cilta-cel), with stable disease or better, receive cevo starting 10-12 weeks (wks) post-CART at step-up dose of 3.6mg IV on Cycle 1 Day 1 (C1D1), followed by 132mg starting C1D8, then q3wks for total of 8 cycles...Median number of prior lines was 4 (2-10), with 74% triple-class refractory, 11% prior BCMA therapy, and 11% prior talquetamab... To date, cevostamab consolidation post-CAR T cell infusion appears feasible and well-tolerated in late-line RRMM, with low rates of non-hematologic G3/4 TEAEs, including infections. Preliminary efficacy appears promising, with over 90% showing sustained MRD-negative sCR at 1 year."

CAR T-Cell Therapy • Clinical • IO biomarker • Late-breaking abstract • P2 data • Ataxia • Autoimmune Hepatitis • Cough • Gastroenterology • Gastrointestinal Disorder • Hematological Malignancies • Hepatology • Immunology • Infectious Disease • Inflammation • Movement Disorders • Multiple Myeloma • Neutropenia • Respiratory Diseases • Thrombocytopenia

Enduring Responses after 1-Year, Fixed-Duration Cevostamab Therapy in Patients with Relapsed/Refractory Multiple Myeloma: Early Experience from a Phase I Study (ASH 2022) - P1 | "Early data from this Phase I study suggest that patients can maintain durable responses (≥6 months) after completion of 17 cycles of cevostamab treatment, highlighting the potential for an extended treatment-free period following fixed-duration therapy. Further data are needed to confirm the duration of response and associated correlates following completion of treatment. Additional data on responding patients with premature discontinuation of treatment (i.e."

Clinical • P1 data • Hematological Malignancies • Infectious Disease • Inflammation • Multiple Myeloma • Oncology • Pneumonia • Respiratory Diseases

CEVOSTAMAB IN PATIENTS WITH RRMM WHO ARE TRIPLE-CLASS REFRACTORY AND HAVE RECEIVED A PRIOR BCMA-TARGETED ADC OR CAR T-CELL: INITIAL RESULTS FROM THE PHASE I/II CAMMA 2 STUDY (EHA 2024) - P1/2 | "CRS was managed with tocilizumab (7 pts) or steroids(8 pts); 1 patient received both. Initial data from Cohort A1 of CAMMA 2 demonstrate that cevostamab has promising activity and manageablesafety in pts with RRMM who are triple-class refractory and have received a prior BCMA-targeted ADC or CART-cell therapy."

CAR T-Cell Therapy • Clinical • IO biomarker • P1/2 data • Anemia • CNS Disorders • Epilepsy • Hematological Disorders • Hematological Malignancies • Infectious Disease • Inflammation • Multiple Myeloma • Neutropenia • Oncology • Thrombocytopenia • IL6

Cevostamab Plus Pomalidomide (Pom) and Dexamethasone (dex) in Relapsed/Refractory Multiple Myeloma (RRMM): Phase I Dose-Expansion Results from the CAMMA 1 Study (IMS 2025) - P1 | "Cevostamab plus Pom and dex induces deep responses and has manageable safety in RRMM. Updated data from the Arm B dose expansion will be presented, including initial data from 32 additional pts in Arm B3E who received triple step-up dosing, and emerging biomarker analyses, including minimal residual disease, which will confirm the pattern of response and AEs with the LD and HD regimens."

IO biomarker • P1 data • Anemia • Cardiovascular • Hematological Disorders • Hematological Malignancies • Infectious Disease • Inflammation • Multiple Myeloma • Neutropenia • Pneumonia • Respiratory Diseases • Thrombocytopenia

Cevostamab in Patients with Heavily Pretreated Relapsed/Refractory Multiple Myeloma (RRMM): Updated Results from an Ongoing Phase I Study Demonstrate Clinically Meaningful Activity and Manageable Safety and Inform the Doses and Regimen for Combination Studies (ASH 2024) - P1 | "Pts with CRS were managed with tocilizumab (47.4%), steroids (21.1%), or both agents (10.5%). C1 TS dosing provides effective CRS mitigation. Cevostamab combination studies may use the 0.3/1.2/3.6mg TS regimen and the Q3W 160mg TD (or similar TD exposure)."

Clinical • P1 data • Anemia • Cough • Fatigue • Hematological Disorders • Hematological Malignancies • Hemophagocytic lymphohistiocytosis • Immunology • Infectious Disease • Inflammation • Multiple Myeloma • Neutropenia • Oncology • Rare Diseases • Respiratory Diseases • Septic Shock

Novel combination immunotherapy for relapsed/refractory multiple myeloma (RRMM): initial Phase 1 safety run-in results for cevostamab in combination with pomalidomide and dexamethasone (IMW 2023) - P1 | "Both daratumumab (dara), an anti-CD38 antibody, and pomalidomide (pom), an immunomodulatory drug (IMiD), exhibit T-cell co-stimulatory effects and are clinically active when administered alone or with dexamethasone (dex) in pts with RRMM (Lonial et al. Cevostamab plus pom and dex shows promising activity in pts with RRMM and warrants further evaluation to optimize the benefit/risk profile. Biomarker and updated clinical data will be presented."

Clinical • Combination therapy • IO biomarker • P1 data • Hematological Disorders • Hematological Malignancies • Multiple Myeloma • Neutropenia • Oncology

Pretreatment with Tocilizumab Prior to the CD3 Bispecific Cevostamab in Patients with Relapsed/Refractory Multiple Myeloma (RRMM) Showed a Marked Reduction in Cytokine Release Syndrome Incidence and Severity (ASH 2022) - P1 | "Pts in both arms received corticosteroid, antihistamine and acetaminophen premedication prior to cevostamab. Clinical data from the GO39775 study shows for the first time that TCZ pretreatment can significantly reduce the risk of developing TDB-induced CRS without an apparent impact on anti-myeloma activity. The data support additional investigation of the use of anti-cytokine pretreatment with the goal of substantially reducing the frequency and potentially the severity of CRS."

Clinical • Cytokine release syndrome • Hematological Disorders • Hematological Malignancies • Hepatology • Infectious Disease • Inflammation • Multiple Myeloma • Neutropenia • Oncology • Thrombocytopenia • Transplantation • CRP • IL6 • TNFA

CAMMA 1: A Study Evaluating the Safety, Pharmacokinetics, and Activity of Cevostamab in Participants With Relapsed or Refractory Multiple Myeloma (clinicaltrials.gov) - P1 | N=126 | Active, not recruiting | Sponsor: Genentech, Inc. | Trial primary completion date: Dec 2025 ➔ Dec 2029 | Trial completion date: Dec 2025 ➔ Dec 2029

Monotherapy • Trial completion date • Trial primary completion date • Hematological Malignancies • Multiple Myeloma • Oncology

Cevostamab Following CAR T Cell Therapy for RRMM (clinicaltrials.gov) - P2 | N=30 | Active, not recruiting | Sponsor: University of Pennsylvania | Recruiting ➔ Active, not recruiting

Enrollment closed • Hematological Malignancies • Multiple Myeloma • Oncology

Tumor intrinsic mechanisms leading to cevostamab resistance in multiple myeloma (ASH 2025) - "Allpatients had previously been treated with both immunomodulatory drugs (IMiDs) and proteasomeinhibitors (PI) and eight patients had received daratumumab prior to cevostamab, which was, on average,the 6th line of treatment (mean treatment duration 220±273 days). Due to thelimited sample size, these findings require validation in larger cohorts. Nonetheless, our findings begin toelucidate tumor intrinsic mechanisms associated with cevostamab resistance."

IO biomarker • Hematological Malignancies • Multiple Myeloma • Oncology • SDC1

Tumor clearance, T-cell fitness, and minimal residual disease (MRD) outcomes in patients with relapsed/refractory multiple myeloma (RRMM) treated with cevostamab plus pomalidomide and dexamethasone: Biomarker analyses from CAMMA 1 Arm B (ASH 2025) - P1 | "Combination treatment is also associated with deep and durable declines insBCMA levels and high rates of CR+MRD-negativity. Updated biomarker data will be presented, includingbaseline immune fitness and correlation with MRD negativity."

Biomarker • Clinical • IO biomarker • Minimal residual disease • Residual disease • Hematological Malignancies • Multiple Myeloma • Oncology • CD8

Cevostamab Consolidation After BCMA CAR T-Cell Therapy for Patients With R/R Multiple Myeloma: "STEM" Trial (HMPL Global) - "Getting to the efficacy data, 63% of patients were already incomplete response when they entered the trial post-CAR, that number went up to over 80% after 8 cycles. In the patients who are evaluable at the one year mark, so far, it's over 93% of patients in complete response. The 1 year MRD-negative CR rate is 93%."

P2 data • Multiple Myeloma

Endless possibilities and how to exploit them? What is the optimal treatment sequence? (PubMed, Hematology Am Soc Hematol Educ Program) - "For transplant-eligible, transplant-deferred, and fit transplant-ineligible patients who are younger than 80 years old, we use anti-CD38 mAb-, lenalidomide-, and bortezomib/carfilzomib-based quadruplets as an induction regimen. For early relapse (1-3 prior lines), chimeric antigen receptor T-cell therapies targeting B-cell maturation antigen (BCMA) have demonstrated superiority over standard regimens, with ciltacabtagene autoleucel (cilta-cel) being the most efficacious product currently, albeit with some unique toxicities such as parkinsomism...In late relapse (≥4 prior lines), bispecific antibodies (BsAbs) targeting BCMA (teclistamab, elranatamab, and linvoseltamab) and GPRC5D (talquetamab) have demonstrated impressive single-agent activity with distinct toxicity profiles...For patients with BCMA- and GPRC5D-refractory disease, FcRH5-targeting BsAb (cevostamab), BCL2 inhibitors for t(11;14)-positive disease, and novel trispecific antibodies (BCMAXCD38; BCMAXGPRC5D)..."

Journal • Review • Hematological Malignancies • Multiple Myeloma • Oncology • Transplantation

Initial results from the phase 1b CAMMA 3 study (EUDRACT: 2021-002307-36) shared during the 2025 American Society of Hematology (ASH) Annual Meeting and Exposition showed that subcutaneous (SC) cevostamab achieved clinically meaningful activity in patients with relapsed/refractory multiple myeloma (Cancer Network) - "Of 52 efficacy-evaluable patients, the overall response rate (ORR) was 38.8% (95% CI, 24.1%–53.4%) across all tested dose levels. Further, the agent demonstrated a stringent complete response (sCR) in 14.3% of patients, complete response (CR) in 6.1%, very good partial response (VGPR) in 10.2%, and partial response in 8.2%. The median duration of response (DOR) was 12.3 months (95% CI, 8.3–not estimable). Notably, responses were particularly pronounced among those patients who were B-cell maturation antigen (BCMA) therapy-naive, achieving an ORR of 52.0% (95% CI, 30.4%–73.6%) vs 25.0% (95% CI, 5.6%–44.4%) among those who were BCMA-exposed (n = 26, each group)."

P1 data • Multiple Myeloma

Evaluation of Immune Reconstitution in Patients with Relapsed/Refractory Multiple Myeloma (RRMM) Treated with Cevostamab in Phase I Study GO39775 (ASH 2023) - P1 | "At data cut-off (March 1, 2023), a total of 310 patients were enrolled in GO39775. 76 patients met the inclusion criteria and were eligible for analysis. Median age was 65 years (range: 43–82), with a median of 6 previous lines of therapy (range: 2–12)."

Clinical • P1 data • Hematological Malignancies • Infectious Disease • Multiple Myeloma • Oncology

Tocilizumab Prophylaxis for Patients Treated with Teclistamab: A Single-Center Experience (ASH 2023) - "Emerging data from 28 RRMM patients treated with the bispecific antibody cevostamab (targeting FcRH5 and CD3) indicate that use of prophylactic tocilizumab, an anti-IL6 monoclonal antibody, can reduce the risk of developing CRS significantly, without impacting its anti-myeloma activity (Trudel et al. Our findings suggest that tocilizumab may be effective as a preventative, rather than reactive, measure for patients treated with teclistamab. Larger studies are needed to confirm and expand on our results."

Clinical • Hematological Disorders • Hematological Malignancies • Infectious Disease • Multiple Myeloma • Neutropenia • Oncology • Plasmacytoma

High Dimensional Profiling of Patient-Derived Multiple Myeloma Bone Marrow Specimens Treated with an FcRH5-Targeted Bispecific Ex Vivo (ASH 2023) - P, P1 | "Background: Cevostamab is an FcRH5 (Fc receptor-homolog 5) targeted T cell-dependent bispecific (TDB) currently being evaluated in the clinic, with promising activity and favorable safety profile as a monotherapy in patients (pts) with heavily pre-treated Relapsed/Refractory multiple myeloma (MM) (NCT03275103, Trudel et al... We first examined the T cell compartment by scRNA-seq profiling. Upon FcRH5 TDB treatment, clustering analysis suggested that CD4 and CD8 T cells undergo extensive transcriptional changes compared to control TDB (Fig 1A). A TNF and LTA-expressing CD4 memory cluster was enriched upon treatment in both SoRs and Rs, but to a greater extent in Rs."

IO biomarker • Preclinical • Hematological Malignancies • Multiple Myeloma • Oncology • CCND2 • CD38 • CD44 • CD8 • CXCL9 • HLA-E • IFNG • SDC1 • SOCS1 • SRGN • TNFSF10

Pooled Analysis on Bispecific Antibody-Related Toxicities in Multiple Myeloma (ASH 2023) - "BsAb included in our study were the following: Teclistamab, Elranatamab, REGN-5458, AMG420, AMG701, CC-93269, TNB-383B, Linvoseltamab, Talquetamab, and Cevostamab. The use of BsAbs in MM has demonstrated remarkable efficacy; however, these have been linked to a unique adverse event profile. Our results showed that non-BCMA bsAb were associated less hematotoxicity (combined grade 3-4 events and hypogammaglobulinemia), whereas BCMA bsAb were associated with less CRS rates. This is important information for treatment selection and mitigation strategy development aiming to optimize patient outcomes."

Retrospective data • Anemia • Hematological Disorders • Hematological Malignancies • Infectious Disease • Leukopenia • Multiple Myeloma • Neutropenia • Oncology • Thrombocytopenia

MODULE 4: Bispecific Antibodies in the Treatment of MM (ASH 2023) - "Supported by AbbVie Inc, GSK, Janssen Biotech Inc, administered by Janssen Scientific Affairs LLC, Karyopharm Therapeutics, Legend Biotech, Regeneron Pharmaceuticals Inc, and Sanofi. Similarities and differences in the cellular targets and mechanisms of action among bispecific antibodies for MM Antitumor activity observed with teclistamab in the Phase I/II MajesTEC-1 study leading to its recent FDA approval for R/R MM; optimal incorporation into the treatment paradigm Rate, depth and duration of response observed with elranatamab in the pivotal Phase II MagnetisMM-3 trial for patients with R/R MM; FDA approval and current clinical role Key findings with other promising anti-BCMA bispecific antibody constructions, such as alnuctamab, linvoseltamab and ABBV-383, for heavily pretreated MM Available efficacy and safety findings with non-BCMA-targeted bispecific antibodies for MM, such as talquetamab, cevostamab and RG6234; FDA approval of talquetamab for patients with R/R MM..."

Hematological Malignancies • Hodgkin Lymphoma • Lymphoma • Mantle Cell Lymphoma • Oncology

Epigenetic Silencing of Immunotherapy Targets in Multiple Myeloma (DGHO 2025) - "Known genetic drivers: structural variants (SVs), deletions, single-nucleotide variants (SNVs) in target genes, only account for a minority of resistant cases, suggesting alternative mechanisms e.g. epigenetic ones.We performed long-read Nanopore sequencing on sequential bone marrow samples from patients who relapsed to anti-BCMA (CAR T, elranatamab, belantamab) and anti-FCRL5 therapies (cevostamab). Our findings advocate for the clinical integration of methylation profiling as a predictive and monitoring tool to anticipate resistance. The observations of an "epigenetic resistance memory" argues in favour of a broader, underappreciated role in multidrug resistance."

IO biomarker • Hematological Malignancies • Multiple Myeloma • CRBN • DNMT1 • DNMT3A • DNMT3B

MODULE 4: Bispecific Antibodies for the Treatment of MM (ASH 2024) - "This program is supported by educational grants from GSK, Janssen Biotech Inc, administered by Janssen Scientific Affairs LLC and Karyopharm Therapeutics.Available efficacy and safety findings leading to the FDA approvals of the BCMA-directed bispecific antibodies teclistamab and elranatamab for R/R MM; optimal incorporation into management algorithms Efficacy and safety documented with investigational anti-BCMA bispecific antibodies for pretreated MM, such as linvoseltamab and alnuctamab Available efficacy and safety findings with non-BCMA-targeted bispecific antibodies for MM, such as talquetamab and cevostamab Recent FDA approval and optimal incorporation of talquetamab into disease management Spectrum, incidence and severity of CRS and other toxicities with various BCMA- and non-BCMA-directed bispecific antibodies; optimal mitigation and management strategies Rationale for and early-phase data with bispecific antibodies in combination with other systemic therapies,..."

Hematological Malignancies • Multiple Myeloma • Oncology

Tocilizumab Prophylaxis for Patients with Relapsed or Refractory Multiple Myeloma Treated with Teclistamab, Elranatamab or Talquetamab (ASH 2024) - "J Clin Oncol 2023) and the investigational bispecific antibody cevostamab (Trudel et al...A single repeat dose of tocilizumab was given for ICANS and additional dexamethasone was given to 3 patients for ICANS...Conclusions : Our findings build on previous evidence that tocilizumab may be effective as a preventative, rather than reactive, measure for patients treated with a bispecific antibody for RRMM. Larger randomized studies are needed to confirm and expand on our results."

Clinical • Cerebral Hemorrhage • CNS Disorders • Epilepsy • Hematological Disorders • Hematological Malignancies • Infectious Disease • Leukemia • Multiple Myeloma • Neutropenia • Oncology • Plasma Cell Leukemia • Pneumonia • Respiratory Diseases