pavurutamab (AMG 701) / Amgen, BeOne Medicines - LARVOL DELTA

Safety and Efficacy of Anti-B-cell Maturation Antigen (Anti-BCMA) Bispecific Antibodies for Relapsed/Refractory Multiple Myeloma: A Systematic Review of Clinical Trials. (PubMed, Cureus) - "AMG-420, AMG-701, elranatamab, REGN5458, teclistamab (Tec), alnuctamab (ALNUC), and ABBV-383 are the seven anti-BCMA-CD3 bispecific Abs currently being assessed in clinical trials as monotherapy and in combination with immunomodulators/proteasome inhibitors against RRMM. Our analysis of the trials revealed that bispecific Abs showed efficacy in RRMM, with CRS and hematologic toxicities being the most common adverse events, mostly low-grade and manageable. Based on the promising efficacy and safety of BCMA targeting bispecific Abs, these drugs are emerging as a new therapeutic option for patients with advanced and RRMM."

Journal • Review • Hematological Disorders • Hematological Malignancies • Inflammation • Multiple Myeloma • Oncology

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

A Study to Assess AMG 701 Montherapy, or in Combination With Pomalidomide, With or Without, Dexamethasone in Subjects With Relapsed or Refractory Multiple Myeloma (clinicaltrials.gov) - P1 | N=174 | Terminated | Sponsor: Amgen | Phase classification: P1/2 ➔ P1

Combination therapy • Monotherapy • Phase classification • Hematological Malignancies • Multiple Myeloma • Oncology

Sequencing of Bispecific Antibodies in Relapsed Refractory Multiple Myeloma (IMW 2024) - "To date, 3 BsAB have been approved for RRMM, two of which – Teclistamab (tec) and elranatamab (elra) target BCMA, while talquetamab (talq) targets the GPRC5D protein...The most utilized first BsAb was tec (56%), followed by elra (19%), AMG 701 (13%), talq (6%), and cevostamab (cevo) (6%)... Treatment of RRMM remains challenging given the limited options and poor outcomes seen in this population. Our results support the sequential use of BsAbs with an ORR of 38% to second BsAb with an average duration of treatment of 232 days for those remaining on their second BsAb at time of analysis. Despite the clinical benefit observed, infectious complications remain a significant risk of this strategy, requiring close and frequent monitoring."

Febrile Neutropenia • Hematological Malignancies • Infectious Disease • Multiple Myeloma • Novel Coronavirus Disease • Oncology • Pneumonia • Respiratory Diseases • Respiratory Syncytial Virus Infections

Comprehensive assessment of adverse event profiles associated with bispecific T cell engagers in multiple myeloma. (ASCO 2024) - "We found 23 studies which include BCMA agents: teclistamab (Tec), elranatamab, linvoseltamab, pavurutamab, and alnuctamab; and non-BCMA targets including: GPRC5D, talquetamab (Tal) and FcRH5, cevostamab, as well as combination therapies including a BiTE, specifically Tec+Tal and Tal+daratumumab (Tal+D)...More instances of CRS and CRS with Tocilizumab occurred with BCMA BiTEs vs non-BCMA BiTes, P < 0... The use of BiTEs in MM has demonstrated remarkable efficacy; however, these have been linked to a unique AE profile. Our results showed that non-BCMA were associated with less hematotoxicity (combined G3+ AEs and hypogammaglobulinemia), whereas BCMA BiTEs were associated with less CRS rates. This is important information for treatment selection and mitigation strategy development aiming to optimize patient outcomes."

Adverse events • Anemia • Hematological Disorders • Hematological Malignancies • Infectious Disease • Multiple Myeloma • Neutropenia • Oncology • Respiratory Diseases

Effectiveness of anti-B-cell maturation antigen (BCMA)-targeting therapy after selinexor treatment (IMW 2023) - P1b/2, P2b, P3 | "The influence of selinexor-based treatment on T cell function, which may alter the efficacy of αBCMA agents following selinexor treatment, is unknown. We analyzed the effectiveness of non-cellular αBCMA (NCA) therapies in pts with MM treated in 4 clinical studies (STORM [NCT02336815]; STOMP [NCT02343042]; BOSTON [NCT03110562], XPORT-MM-028 [NCT04414475]) with selinexor + dexamethasone (Xd), with or without PIs, IMiDs, or αCD38 mAbs, followed by therapy with NCA...Thirty-seven pts (median age: 68, range: 40-87) received NCA therapy at any time following a selinexor regimen (Xd, n=12; Xd + bortezomib, n=9; Xd + pomalidomide, n=6; Xd + daratumumab, n=3; Xd + carfilzomib, n=5; Xd + ixazomib, n=2). NCAs included the ADC belantamab mafodotin (n=28), the BiS teclistamab (n=2), SEA-BCMA (n=2), AMG 701 (n=1), elranatamab (n=1), MEDI2228 (n=1), and investigational (n=3; 2 had αBCMA bispecific antibodies and 1 had αBCMA BITE) (1 pt received 2 NCAs, belantamab and..."

Hematological Malignancies • Multiple Myeloma • Oncology

A Study to Assess AMG 701 Montherapy, or in Combination With Pomalidomide, With or Without, Dexamethasone in Subjects With Relapsed or Refractory Multiple Myeloma (clinicaltrials.gov) - P1/2 | N=174 | Terminated | Sponsor: Amgen | Completed ➔ Terminated; business decision, not safety reasons.

Combination therapy • Monotherapy • Trial termination • Hematological Malignancies • Multiple Myeloma • Oncology

A Study to Assess AMG 701 Montherapy, or in Combination With Pomalidomide, With or Without, Dexamethasone in Subjects With Relapsed or Refractory Multiple Myeloma (clinicaltrials.gov) - P1/2 | N=174 | Completed | Sponsor: Amgen | Active, not recruiting ➔ Completed | Trial completion date: Aug 2027 ➔ Jun 2023

Combination therapy • Monotherapy • Trial completion • Trial completion date • Hematological Malignancies • Multiple Myeloma • Oncology

Effectiveness of anti-B-cell maturation antigen (BCMA)-targeting therapy after selinexor treatment. (ASCO 2023) - P1b/2, P2b, P3 | " We analyzed the effectiveness of non-cellular αBCMA (NCA) therapies in pts with MM treated in 4 clinical studies (STORM [NCT02336815]; STOMP [NCT02343042]; BOSTON [NCT03110562], XPORT-MM-028 [NCT04414475]) with selinexor + dexamethasone (Xd), with or without PIs, IMiDs, or αCD38 mAbs, followed by therapy with NCA...Thirty-seven pts (median age: 68, range: 40-87) received NCA therapy at any time following a selinexor regimen (Xd, n = 12; Xd + bortezomib, n = 9; Xd + pomalidomide, n = 6; Xd + daratumumab, n = 3; Xd + carfilzomib, n = 5; Xd + ixazomib, n = 2). NCAs included the ADC belantamab mafodotin (n = 28), the BiS teclistamab (n = 2), SEA-BCMA (n = 2), AMG 701 (n = 1), elranatamab (n = 1), MEDI2228 (n = 1), and investigational (n = 3; 2 had αBCMA bispecific antibodies and 1 had αBCMA BITE) (1 pt received 2 NCAs, belantamab and teclistamab)... In this cohort of heavily-pretreated pts with MM who received a selinexor regimen prior to NCA, overall..."

Hematological Malignancies • Immune Modulation • Multiple Myeloma • Oncology

Bispecific Antibodies in the Treatment of Multiple Myeloma: An Expert Case-Based Discussion : Episode 11: Bispecific Antibodies Promise to be ‘Transformative’ in Multiple Myeloma (Cancer Network) - "At a recent Around the Practice program, experts spoke about recent advances in multiple myeloma, including the approval of teclistamab-cqyv (Tecvayli), the utility of the FDA's accelerated approval process, and the promise of bispecific antibodies generally....Patel: Those [response rates] are phenomenal. We're all millennial doctors who [began working] in the last 10 years, [and], for us, this is going to be the new normal. [Even] if you see something lower than [those rates], it's still good."

Media quote

AMG 701 Potently Induces Anti-Multiple Myeloma (MM) Functions of T Cells and IMiDs Further Enhance Its Efficacy to Prevent MM Relapse In Vivo (ASH 2019) - P1; "Combination of AMG 701 and len significantly induced superior MM cell regression, compared to either monotherapy, resulting in enhanced tumor regression and prevention of disease relapse. Taken together, these results strongly support AMG 701-based clinical studies, both as monotherapy (NCT03287908) and in combination with IMiDs to enhance elimination of residual diseases and prolong long-term durable responses in MM."

IO Biomarker • Preclinical • CD8 • IFNG

Anti-Bcma BiTE® AMG 701 Potently Induces Specific T Cell Lysis of Human Multiple Myeloma (MM) Cells and Immunomodulation in the Bone Marrow Microenvironment (ASH 2018) - P1; "We here show that AMG 701 significantly induced T cell-mediated lysis of BCMA-positive MM cells resistant or sensitive to current anti-MM agents including bortezomib and lenalidomide (len). Taken together, these results demonstrate that AMG 701 potently induces T cell-directed lysis of BCMA-positive MM cells in and triggers robust immunomodulatory effects to overcome the immunocompromised BM microenvironment. Moreover, these results provide the rationale for clinical trials based of AMG 701, alone and in combination with lenalidomide, to improve patient outcome in MM."

IO biomarker • PD(L)-1 Biomarker • Biosimilar • Hematological Disorders • Hematological Malignancies • Immune Modulation • Inflammation • Multiple Myeloma • Oncology

Efficacy and safety of cilta-cel in patients with progressive multiple myeloma after exposure to BCMA-targeting bispecific antibody treatment (IMW 2022) - P2 | "Of the patients who received cilta-cel, 3 had prior teclistamab, and 1 each had prior AMG 420, AMG 701, PF06863135, and WVT078. Cilta-cel induced favorable responses, DOR, and PFS in heavily pretreated MM patients with prior anti-BCMA BsAb exposure. These initial results may inform treatment plans, including sequencing and washout periods between agents targeting BCMA."

Clinical • CNS Disorders • Gastroenterology • Gastrointestinal Disorder • Hematological Disorders • Hematological Malignancies • Immune Modulation • Immunology • Infectious Disease • Inflammation • Movement Disorders • Multiple Myeloma • Novel Coronavirus Disease • Oncology • Parkinson's Disease • Pneumonia • Respiratory Diseases • Subarachnoid Hemorrhage

A Study to Assess AMG 701 Montherapy, or in Combination With Pomalidomide, With or Without, Dexamethasone in Subjects With Relapsed or Refractory Multiple Myeloma (clinicaltrials.gov) - P1/2 | N=174 | Active, not recruiting | Sponsor: Amgen | Recruiting ➔ Active, not recruiting | N=408 ➔ 174

Combination therapy • Enrollment change • Enrollment closed • Monotherapy • Hematological Malignancies • Multiple Myeloma • Oncology

A Study to Assess AMG 701 Montherapy, or in Combination With Pomalidomide, With or Without, Dexamethasone in Subjects With Relapsed or Refractory Multiple Myeloma (clinicaltrials.gov) - P1/2 | N=408 | Recruiting | Sponsor: Amgen | Trial completion date: Apr 2029 ➔ Aug 2027 | Trial primary completion date: Oct 2024 ➔ Jul 2023

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

A Study to Assess AMG 701 Montherapy, or in Combination With Pomalidomide, With or Without, Dexamethasone in Subjects With Relapsed or Refractory Multiple Myeloma (clinicaltrials.gov) - P1/2 | N=408 | Recruiting | Sponsor: Amgen | Trial completion date: Apr 2028 ➔ Apr 2029 | Trial primary completion date: Oct 2023 ➔ Oct 2024

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

ProxiMMity-1: A Study of Subcutaneous (SC) AMG 701 in Participants With Relapsed or Refractory Multiple Myeloma (RRMM) (clinicaltrials.gov) - P1b | N=0 | Withdrawn | Sponsor: Amgen | N=47 ➔ 0 | Trial completion date: Aug 2024 ➔ Aug 2025 | Not yet recruiting ➔ Withdrawn | Trial primary completion date: Aug 2024 ➔ Aug 2025

Enrollment change • Trial completion date • Trial primary completion date • Trial withdrawal • Hematological Malignancies • Multiple Myeloma • Oncology

AMGEN REPORTS SECOND QUARTER 2022 FINANCIAL RESULTS (PRNewswire) - "Pavurutamab (AMG 701): Clinical development of pavurutamab an anti-B-cell maturation antigen (BCMA) HLE BiTE molecule being investigated for the treatment of multiple myeloma, has been discontinued for strategic reasons."

Discontinued • Hematological Malignancies • Multiple Myeloma • Oncology

ProxiMMity-1: A Study of Subcutaneous (SC) AMG 701 in Participants With Relapsed or Refractory Multiple Myeloma (RRMM) (clinicaltrials.gov) - P1b | N=47 | Not yet recruiting | Sponsor: Amgen | Trial completion date: May 2024 ➔ Aug 2024 | Initiation date: May 2022 ➔ Aug 2022 | Trial primary completion date: May 2024 ➔ Aug 2024

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

AMG 701 Expanded Access Program (clinicaltrials.gov) - P=N/A | N=N/A | Available | Sponsor: Amgen

New trial

A Study to Assess AMG 701 Montherapy, or in Combination With Pomalidomide, With or Without, Dexamethasone in Subjects With Relapsed or Refractory Multiple Myeloma (clinicaltrials.gov) - P1/2; N=408; Recruiting; Sponsor: Amgen; Trial completion date: Nov 2027 ➔ Apr 2028

Clinical • Combination therapy • Monotherapy • Trial completion date • Hematological Malignancies • Multiple Myeloma • Oncology

ProxiMMity-1: A Study of Subcutaneous (SC) AMG 701 in Participants With Relapsed or Refractory Multiple Myeloma (RRMM) (clinicaltrials.gov) - P1b; N=47; Not yet recruiting; Sponsor: Amgen; Trial completion date: Dec 2024 ➔ Feb 2024; Trial primary completion date: Jun 2024 ➔ Jan 2024

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

[VIRTUAL] A Phase 1 First in Human (FIH) Study of AMG 701, an Anti-B-Cell Maturation Antigen (BCMA) Half-Life Extended (HLE) BiTE® (bispecific T-cell engager) Molecule, in Relapsed/Refractory (RR) Multiple Myeloma (MM) (ASH 2020) - P1/2 | "All grade 3 CRS (n=5, 7%) were assessed as dose-limiting toxicities (DLTs); all were reversible with corticosteroids and tocilizumab, with median duration of 2 days. As of July 2, 2020, 75 patients received AMG 701. Patients had a median age of 63 years, a median time since diagnosis of 5.9 years, and a median (range) of 6 (1-25) prior lines of therapy; 27% of patients had extramedullary disease, 83% prior SCT, and 93% prior anti-CD38 Ab; 68% were triple refractory to a PI, an IMiD, and an anti‑CD38 Ab. Median (Q1, Q3) treatment duration was 6.1 (3.1, 15.3) weeks and median follow-up on treatment was 1.7 (1.0, 3.7) months."

IO biomarker • P1 data • Atrial Fibrillation • Cardiovascular • CNS Disorders • Fatigue • Hematological Malignancies • Infectious Disease • Metabolic Disorders • Multiple Myeloma • Neutropenia • Oncology • Pneumonia • Respiratory Diseases • Septic Shock • Thrombocytopenia • Transplantation • CD38

ProxiMMity-1: A Study of Subcutaneous (SC) AMG 701 in Participants With Relapsed or Refractory Multiple Myeloma (RRMM) (clinicaltrials.gov) - P1b; N=47; Not yet recruiting; Sponsor: Amgen

New P1 trial • Hematological Malignancies • Multiple Myeloma • Oncology • PCR

Another one BiTEs the dust as Amgen pauses enrollment for phase 1 bispecific trial (FierceBiotech) - "Amgen disclosed the resumption of enrollment in the study of BCMA BiTE pavurutamab during the second-quarter update. Enrollment for the multiple myeloma clinical trial was paused while the company discussed 'protocol modifications to optimize safety monitoring and mitigation with the FDA.'....Amgen is yet to restart enrollment in the paused CD33 and EGFR studies. The CD33 study is paused pending the generation of 'further information on the CD33 program through progression of AMG 330.' Amgen stopped the EGFR study as it prioritized its portfolio."

Enrollment open • Trial termination • Hematological Malignancies • Multiple Myeloma • Oncology