REGN5668 / Regeneron - LARVOL DELTA

A CD38xCD28 Costimulatory Bispecific Antibody Demonstrates Potent Preclinical Combinatorial Activity with a BCMAxCD3 T Cell-Engager (ASH 2024) - "In RRMM, linvoseltamab activates T cells by engaging the T cell receptor (TCR)/CD3 complex in the presence of BCMA-expressing MM tumor cells leading to tumor cell killing...CD28-targeting bsAbs, including REGN5668 (MUC16xCD28) and REGN5837 (CD22xCD28), are an emerging class of therapeutics capable of providing targeted costimulation and enhancing T cell effector function in combination with CD3-targeted bsAbs...Based on these promising preclinical results, a Phase 1 clinical trial is planned to evaluate the safety, tolerability, and preliminary efficacy of the CD38xCD28 bsAb REGN7945 and the BCMAxCD3 bsAb linvoseltamab in patients with RRMM. This innovative approach, leveraging the combinatorial potential of CD38xCD28 costimulation with linvoseltamab's targeted cytolytic activity, represents a novel therapeutic strategy with the potential to improve RRMM treatment outcomes."

Preclinical • Hematological Malignancies • Multiple Myeloma • Oncology • CD28

R5668-ONC-1938: A Trial to Find Out How Safe REGN5668 is and How Well it Works When Given With Either Cemiplimab or REGN4018 (clinicaltrials.gov) - P1/2 | N=612 | Recruiting | Sponsor: Regeneron Pharmaceuticals | N=326 ➔ 612 | Trial primary completion date: Jan 2027 ➔ Apr 2027

Combination therapy • Enrollment change • Trial primary completion date • Endometrial Cancer • Fallopian Tube Cancer • Oncology • Ovarian Cancer • Peritoneal Cancer • Solid Tumor

Regeneron to Share Progress of Novel Combination Therapies in Oncology at ESMO IO (GlobeNewswire) - P1/2 | N=326 | NCT04590326 | Sponsor: Regeneron Pharmaceuticals | "Regeneron Pharmaceuticals, Inc...announced the presentation of new and updated data on multiple combination therapies from its oncology pipeline at the European Society for Medical Oncology Immuno-Oncology (ESMO IO) Congress 2023 from December 6 to 8 in Geneva, Switzerland. Highlights include first Phase 1 dose-escalation data for the investigational costimulatory bispecific antibody REGN5668 (MUC16xCD28) in combination with PD-1 inhibitor Libtayo® (cemiplimab) showing encouraging initial activity in patients with recurrent ovarian cancer....At the time of initial data cut off (July 14, 2023), 6 patients (21%) had stable disease, while 1 patient (in the 300 mg REGN5668 cohort) had an ongoing confirmed partial response with a 59% target lesion reduction from baseline."

P1/2 data • Gynecologic Cancers • Oncology • Ovarian Cancer • Solid Tumor

REGN5668 (MUC16xCD28 bispecific antibody) with cemiplimab (anti-PD-1 antibody) in recurrent ovarian cancer: Phase 1 dose-escalation study (ESMO-IO 2023) - P1/2 | "Clinical trial identification NCT04590326. Conclusions In 28 heavily pretreated OC pts, an acceptable safety profile, low rates of CRS, and early activity were observed with R5668 + cemi. R5668 dose escalation with cemi or ubamatamab (MUC16xCD3 bsAb) is ongoing."

P1 data • Oncology • Ovarian Cancer • Solid Tumor • IFNG • MUC16

A Phase I/II, multicenter, open-label study of REGN5668 (R5668; mucin [MUC]16 x CD28 bispecific antibody [bsAb]) with cemiplimab or REGN4018 (R4018; MUC16 x CD3 bsAb) in patients with recurrent ovarian cancer (SGO 2023) - No abstract available

Clinical • P1/2 data • Oncology • Ovarian Cancer • Solid Tumor • MUC16

R5668-ONC-1938: Study of REGN5668 Administered in Combination With Cemiplimab or REGN4018 in Adult Women With Recurrent Ovarian Cancer (clinicaltrials.gov) - P1/2 | N=326 | Recruiting | Sponsor: Regeneron Pharmaceuticals | Trial completion date: Jul 2026 ➔ Jul 2027 | Trial primary completion date: Jul 2026 ➔ Jan 2027

Combination therapy • Trial completion date • Trial primary completion date • Fallopian Tube Cancer • Oncology • Ovarian Cancer • Peritoneal Cancer • Solid Tumor

R5668-ONC-1938: Study of REGN5668 Administered in Combination With Cemiplimab or REGN4018 in Adult Women With Recurrent Ovarian Cancer (clinicaltrials.gov) - P1/2 | N=326 | Recruiting | Sponsor: Regeneron Pharmaceuticals | Trial completion date: Feb 2026 ➔ Jul 2026 | Trial primary completion date: Feb 2026 ➔ Jul 2026

Combination therapy • Trial completion date • Trial primary completion date • Fallopian Tube Cancer • Oncology • Ovarian Cancer • Peritoneal Cancer • Solid Tumor

Phase I/II, multicenter, open-label study of REGN5668 (R5668; mucin [MUC]16 x CD28 bispecific antibody [bsAb]) with cemiplimab or REGN4018 (R4018; MUC16 x CD3 bsAb) in recurrent ovarian cancer (rOVCA) (EACR 2022) - P1/2 | "Exclusion criteria include recent biologic therapy (7 days); approved conventional therapy (except biologics or immunotherapy) <3 weeks (wks) or investigational agents <4 wks prior to first study dose; and anti–PD-L1 therapy <5 T 1/2 prior to first study dose. Key exploratory endpoints are correlation between clinical efficacy endpoints and baseline protein expression levels of MUC16 and PD-L1. Results and Discussions NA Conclusion NA"

Clinical • IO biomarker • P1/2 data • Immune Modulation • Inflammation • Oncology • Ovarian Cancer • Peritoneal Cancer • Sarcoma • Solid Tumor • MUC16

[VIRTUAL] A phase I/II, multicenter, open-label study of REGN5668 (mucin [MUC]16 x CD28 bispecific antibody [bsAb]) with cemiplimab (programmed death [PD]-1 Ab) or REGN4018 (MUC16 x CD3 bsAb) in recurrent ovarian cancer (rOVCA). (ASCO 2021) - P1/2 | "Exclusion criteria include recent biologic therapy ( 7 days); approved conventional therapy (except biologics or immunotherapy) < 3 weeks (wks) or investigational agents < 4 wks prior to first study dose; and anti–PD-L1 therapy < 5 half-lives prior to first study dose . In expansion, primary endpoint is ORR by RECIST 1.1 for each combination; key secondary endpoints are TEAEs, serious AEs, deaths . Key exploratory endpoints are correlation between clinical efficacy endpoints and baseline protein expression levels of MUC16 and PD-L1."

Clinical • IO biomarker • P1/2 data • Immune Modulation • Inflammation • Oncology • Ovarian Cancer • Peritoneal Cancer • Sarcoma • Solid Tumor • MUC16 • PD-L2

Libtayo (cemiplimab-rwlc) Presentations at ASCO Highlight Expanding Clinical Data in Diverse Cancers (PRNewswire) - “Regeneron Pharmaceuticals, Inc…announced the company will share a range of presentations for its PD-1 inhibitor Libtayo® (cemiplimab-rwlc) and broader oncology portfolio at the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting from June 4-8, taking place virtually. Presentations include new clinical data and in-depth analyses on the impact of Libtayo in several advanced cancers, including non-small cell lung cancer (NSCLC), cutaneous squamous cell carcinoma (CSCC), basal cell carcinoma (BCC) and melanoma.”

Clinical data • Basal Cell Carcinoma • Gynecologic Cancers • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Squamous Cell Carcinoma • Squamous Cell Skin Cancer

Study of REGN5668 Administered in Combination With Cemiplimab or REGN4018 in Adult Women With Recurrent Ovarian Cancer. (clinicaltrials.gov) - P1/2; N=290; Recruiting; Sponsor: Regeneron Pharmaceuticals; Not yet recruiting ➔ Recruiting

Clinical • Combination therapy • Enrollment open • Fallopian Tube Cancer • Oncology • Ovarian Cancer • Peritoneal Cancer • Sarcoma • Solid Tumor

Study of REGN5668 Administered in Combination With Cemiplimab or REGN4018 in Adult Women With Recurrent Ovarian Cancer. (clinicaltrials.gov) - P1/2; N=290; Not yet recruiting; Sponsor: Regeneron Pharmaceuticals

Clinical • Combination therapy • New P1/2 trial • Fallopian Tube Cancer • Oncology • Ovarian Cancer • Peritoneal Cancer • Sarcoma • Solid Tumor