vonsetamig (REGN5459) / Regeneron, Sanofi - LARVOL DELTA

REGN5459 Spurs Positive Responses in R/R Myeloma (Targeted Oncology) - P1/2 | N=43 | NCT04083534 | Sponsor: Regeneron Pharmaceuticals | "At a median follow-up of 9 months (range, 1-32), in the total population (N = 43), the objective response rate (ORR) was 65.1%, which included a very good partial response (VGPR) or better rate of 58.1% and a complete response (CR) of 51.2%....Additional efficacy data demonstrated that the ORR was 90.5% with higher doses of REGN5459 ranging from 480 mg to 900 mg (n = 21); the VGPR or better and CR rates were 76.2% and 61.9%, respectively. Among 9 patients who received between 120 mg and 240 mg of REGN5459, the ORR was 66.7%, including a 22.2% CR rate and 44.4% stringent CR (sCR) rate."

P1/2 data • Hematological Malignancies • Multiple Myeloma • Oncology

An Observational Extension Study for Adult Patients Treated in Study R5459-RT-1944 Who Receive a Kidney Transplant (clinicaltrials.gov) - P=N/A | N=20 | Recruiting | Sponsor: Regeneron Pharmaceuticals | N=12 ➔ 20 | Trial completion date: May 2026 ➔ Dec 2027

Enrollment change • Trial completion date • Chronic Kidney Disease • Nephrology • Renal Disease • Transplantation

A Study to Learn How Safe and Tolerable Vonsetamig is in Adult Patients With Chronic Kidney Disease (CKD) Who Need Kidney Transplantation and Are Highly Sensitized to Human Leukocyte Antigen (HLA) (clinicaltrials.gov) - P1/2 | N=56 | Recruiting | Sponsor: Regeneron Pharmaceuticals | Trial completion date: Oct 2025 ➔ Jan 2027 | Trial primary completion date: Oct 2025 ➔ Feb 2026

Trial completion date • Trial primary completion date • Chronic Kidney Disease • Nephrology • Renal Disease • Transplantation

An Observational Extension Study for Adult Patients Treated in Study R5459-RT-1944 Who Receive A Kidney Transplant (clinicaltrials.gov) - P=N/A | N=12 | Recruiting | Sponsor: Regeneron Pharmaceuticals | Trial completion date: Mar 2025 ➔ May 2026 | Trial primary completion date: Mar 2025 ➔ May 2026

Trial completion date • Trial primary completion date • Chronic Kidney Disease • Nephrology • Renal Disease • Transplantation

First In Human (FIH) Study of REGN5459 in Adult Patients With Relapsed or Refractory Multiple Myeloma (MM) (clinicaltrials.gov) - P1/2 | N=43 | Active, not recruiting | Sponsor: Regeneron Pharmaceuticals | Trial completion date: Nov 2023 ➔ Nov 2025 | Trial primary completion date: Aug 2023 ➔ Aug 2025

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

An Observational Extension Study for Adult Patients Treated in Study R5459-RT-1944 Who Receive A Kidney Transplant (clinicaltrials.gov) - P=N/A | N=12 | Recruiting | Sponsor: Regeneron Pharmaceuticals | Not yet recruiting ➔ Recruiting | Trial completion date: May 2026 ➔ Mar 2025 | Trial primary completion date: May 2026 ➔ Mar 2025

Enrollment open • Trial completion date • Trial primary completion date • Chronic Kidney Disease • Nephrology • Renal Disease • Transplantation

BCMAxCD3 Bispecific Yields Robust Responses in Myeloma. (PubMed, Cancer Discov) - "In emerging data from a phase I/II trial, patients with relapsed/refractory multiple myeloma responded well to REGN5459, an investigational BCMA-targeting bispecific T-cell engager. However, despite the drug's low affinity for CD3 on T cells, this design did not mitigate the risk of cytokine release syndrome, a common toxicity."

Journal • Hematological Malignancies • Inflammation • Multiple Myeloma • Oncology

Safety and efficacy from the phase 1/2 first-in-human study of REGN5459, a BCMA×CD3 bispecific antibody with low CD3 affinity, in patients with relapsed/refractory multiple myeloma (AACR 2023) - "Tocilizumab was used in 19% and steroids in 9% of pts. These initial data show that REGN5459 has acceptable safety/tolerability in R/R MM with most CRS of low grade and low incidence of ICANS. Modulation of CD3 affinity on bispecific Abs to maximize tumor killing, and mitigate CRS and T-cell exhaustion, warrants further research. Efficacy in this heavily pre-treated cohort was encouraging, with 100% ORR with the RP2D."

Clinical • P1/2 data • Hematological Malignancies • Lung Cancer • Multiple Myeloma • Oncology • Plasmacytoma • Solid Tumor

Bispecific antibody REGN5459 targeting BCMA and CD3 may be useful for relapsed/refractory multiple myeloma [AACR 2023] [Google translation] (Nikkei) - P1/2 | N=43 | NCT04083534 | Sponsor: Regeneron Pharmaceuticals | "REGN5459, a bispecific antibody that targets BCMA on multiple myeloma cells and CD3 on T cells , may be useful for relapsed/refractory multiple myeloma rice field. It was well tolerated in phase 1/2 trials and confirmed promising anti-tumor effects. At the American Association for Cancer Research Annual Meeting 2023 (AACR2023) held in Orlando from April 14 to 19...The study showed an overall response rate of 65.1% with a database cut-off of 8 December 2022 and a median follow-up of 9 months (1-32). VGPR or higher was 58.1% and CR or higher was 51.2%. In 21 patients receiving 480-900 mg, the response rate was 90.5%, 76.2% VGPR or better, and 61.9% CR or better. Of the 19 patients who were evaluable for measurable residual disease (MRD) among the 22 who achieved a CR or better, 15 were MRD-negative with a threshold of 10-5."

P1/2 data • Hematological Malignancies • Multiple Myeloma • Oncology

"So $REGN reports 90.5% ORR with highest doses of REGN5459. I still see tox problems though #AACR23 slides via Attaya Suvannasankha:" (@JacobPlieth)

Oncology

A Dose Escalation and Proof-of-Concept Study of REGN5459 or REGN5458 (BCMAxCD3 Bispecific Antibodies) for Desensitization of Hemodialysis Patients Who Are Highly Sensitized to Human Leukocyte Antigen (KIDNEY WEEK 2022) - P=N/A, P1/2 | "Secondary objectives include determining dosing regimen(s) that result in a clinically meaningful reduction of anti-HLA alloantibody levels, the effect on cPRA levels and circulating immunoglobulin isotypes, pharmacokinetics, and immunogenicity. In a companion study (NCT05106387), patients enrolled in NCT05092347 who receive a kidney transplant will be followed for 1 year to assess rates of adverse events, graft survival, rates and classification of rejection, and emergence of anti-HLA alloantibodies."

Clinical • Antibody-mediated Rejection • Chronic Kidney Disease • Hematological Malignancies • Multiple Myeloma • Nephrology • Oncology • Renal Disease • Transplantation

A Dose Escalation and Proof-of-Concept Study of REGN5459 or REGN5458 (BCMAxCD3 Bispecific Antibodies) for Desensitization of Hemodialysis Patients Who Are Highly Sensitized to Human Leukocyte Antigen (KIDNEY WEEK 2022) - P=N/A, P1/2 | "Secondary objectives include determining dosing regimen(s) that result in a clinically meaningful reduction of anti-HLA alloantibody levels, the effect on cPRA levels and circulating immunoglobulin isotypes, pharmacokinetics, and immunogenicity. In a companion study (NCT05106387), patients enrolled in NCT05092347 who receive a kidney transplant will be followed for 1 year to assess rates of adverse events, graft survival, rates and classification of rejection, and emergence of anti-HLA alloantibodies."

Clinical • Antibody-mediated Rejection • Chronic Kidney Disease • Hematological Malignancies • Multiple Myeloma • Nephrology • Oncology • Renal Disease • Transplantation

A Dose Escalation and Proof-of-Concept Study of REGN5459 or REGN5458 (BCMAxCD3 Bispecific Antibodies) for Desensitization of Hemodialysis Patients Who Are Highly Sensitized to Human Leukocyte Antigen (KIDNEY WEEK 2022) - P=N/A, P1/2 | "Secondary objectives include determining dosing regimen(s) that result in a clinically meaningful reduction of anti-HLA alloantibody levels, the effect on cPRA levels and circulating immunoglobulin isotypes, pharmacokinetics, and immunogenicity. In a companion study (NCT05106387), patients enrolled in NCT05092347 who receive a kidney transplant will be followed for 1 year to assess rates of adverse events, graft survival, rates and classification of rejection, and emergence of anti-HLA alloantibodies."

Clinical • Antibody-mediated Rejection • Chronic Kidney Disease • Hematological Malignancies • Multiple Myeloma • Nephrology • Oncology • Renal Disease • Transplantation

Efficacy and safety of cilta-cel in patients with progressive multiple myeloma after exposure to BCMA-targeting antibody-drug conjugate treatment (IMW 2022) - P2 | "All 13 who received cilta-cel had prior belantamab mafodotin (as last line of therapy [LOT] in 4 patients); 1 had also received MEDI2228 and 1 had also received BCMA-targeting bispecific antibody (REGN5459). MM patients who had previous exposure to an anti-BCMA ADC therapy had favorable responses, DOR, and PFS following cilta-cel. These results may inform treatment plans, including sequencing and washout period between BCMA-targeting agents."

Clinical • CNS Disorders • Hematological Disorders • Hematological Malignancies • Immune Modulation • Infectious Disease • Inflammation • Movement Disorders • Multiple Myeloma • Novel Coronavirus Disease • Oncology • Parkinson's Disease • Pneumonia • Respiratory Diseases

Study for Desensitization of Chronic Kidney Disease Adult Patients in Need of a Kidney Transplant Who Are Highly Sensitized to Human Leukocyte Antigen (clinicaltrials.gov) - P1/2 | N=60 | Recruiting | Sponsor: Regeneron Pharmaceuticals | Not yet recruiting ➔ Recruiting

Enrollment open • Chronic Kidney Disease • Nephrology • Renal Disease • Transplantation

First In Human (FIH) Study of REGN5459 in Adult Patients With Relapsed or Refractory Multiple Myeloma (MM) (clinicaltrials.gov) - P1/2 | N=43 | Active, not recruiting | Sponsor: Regeneron Pharmaceuticals | Trial completion date: Aug 2023 ➔ Nov 2023

Trial completion date • Hematological Malignancies • Multiple Myeloma • Oncology

Study for Desensitization of Chronic Kidney Disease Adult Patients in Need of a Kidney Transplant Who Are Highly Sensitized to Human Leukocyte Antigen (clinicaltrials.gov) - P1/2 | N=60 | Not yet recruiting | Sponsor: Regeneron Pharmaceuticals | Trial completion date: Mar 2025 ➔ Jul 2025 | Trial primary completion date: Mar 2025 ➔ Jul 2025

Trial completion date • Trial primary completion date • Chronic Kidney Disease • Nephrology • Renal Disease • Transplantation

An Observational Extension Study for Adult Patients Treated in Study R5459-RT-1944 Who Receive A Kidney Transplant (clinicaltrials.gov) - P=N/A | N=12 | Not yet recruiting | Sponsor: Regeneron Pharmaceuticals | Trial completion date: Feb 2027 ➔ Jan 2026 | Initiation date: Mar 2022 ➔ Jul 2022 | Trial primary completion date: Feb 2027 ➔ Jan 2026

Trial completion date • Trial initiation date • Trial primary completion date • Chronic Kidney Disease • Nephrology • Renal Disease • Transplantation

First In Human (FIH) Study of REGN5459 in Adult Patients With Relapsed or Refractory Multiple Myeloma (MM) (clinicaltrials.gov) - P1/2; N=43; Active, not recruiting; Sponsor: Regeneron Pharmaceuticals; Recruiting ➔ Active, not recruiting; N=70 ➔ 43; Trial completion date: Mar 2025 ➔ Aug 2023; Trial primary completion date: Feb 2025 ➔ Aug 2023

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

An Observational Extension Study for Adult Patients Treated in Study R5459-RT-1944 Who Receive A Kidney Transplant (clinicaltrials.gov) - P=N/A; N=12; Not yet recruiting; Sponsor: Regeneron Pharmaceuticals

Clinical • New trial • Chronic Kidney Disease • Nephrology • Renal Disease • Transplantation

Study for Desensitization of Chronic Kidney Disease Adult Patients in Need of a Kidney Transplant Who Are Highly Sensitized to Human Leukocyte Antigen (clinicaltrials.gov) - P1/2; N=60; Not yet recruiting; Sponsor: Regeneron Pharmaceuticals

Clinical • New P1/2 trial • Chronic Kidney Disease • Nephrology • Renal Disease • Transplantation

First In Human (FIH) Study of REGN5459 in Adult Patients With Relapsed or Refractory Multiple Myeloma (MM) (clinicaltrials.gov) - P1/2; N=70; Recruiting; Sponsor: Regeneron Pharmaceuticals; Trial completion date: Oct 2023 ➔ Mar 2025; Trial primary completion date: Sep 2023 ➔ Feb 2025

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

First In Human (FIH) Study of REGN5459 in Patients With Relapsed or Refractory Multiple Myeloma (MM) (clinicaltrials.gov) - P1/2; N=56; Recruiting; Sponsor: Regeneron Pharmaceuticals; Not yet recruiting ➔ Recruiting

Clinical • Enrollment open

Newly added product (clinicaltrials.gov) - P1, Multiple Myeloma

Pipeline update