ubamatamab (REGN4018) / Regeneron, Sanofi - LARVOL DELTA

Sarilumab as a potential mitigator of ubamatamab (MUC16×CD3)-induced cytokine release syndrome (CRS) in patients with advanced ovarian cancer (OC) or endometrial cancer (EC) (SITC 2025) - P1/2 | "The research protocol was approved by the relevant institutional review boards or ethics committees at each site. All patients provided written informed consent.Abstract 546 Figure 1Request permissionsSunburst plot of the incidence of CRS by grade over the first 4 weeks of ubamatamab administration in patients treated A) with sarilumab prophylaxis and B) without sarilumab prophylaxisAbstract 546 Figure 2Request permissionsMedian IL-6 (A) and CRP (B) levels in patients treated with and without sarilumab prophylaxis"

Clinical • Cytokine release syndrome • Metastases • Endometrial Cancer • Oncology • Ovarian Cancer • Solid Tumor • CCL11 • CRP • CXCL8 • IFNG • IL6 • MUC16 • TNFA

Bispecific antibody Ubamatamab elicits patient-specific anti-tumor and immune responses in an ex vivo ovarian cancer platform (SITC 2025) - "Micro-tumors including native TME were isolated from fresh ascites (n=12) or pleural fluid (n=2), seeded and exposed to staphylococcus enterotoxin A (SEA) as positive control, single doses of pembrolizumab and dose ranges of chemotherapeutics and ubamatamab (CD3xMUC16 bispecific T cell engaging antibody in Phase 1/2 clinical trials). Our ex vivo 3D micro-tumor platform enables quantification of immune responses and identification of predictive biomarkers that will facilitate patient stratification for novel immunotherapies.Ethics Approval Ovarian cancer patients from the Netherlands were enrolled under a Western IRB-approved protocol into the TUMOVCA study (protocol number IRB P18.032). The IRB (P18.032) reviewed the protocol and confirmed the trial not being subject to the WMO, as patients received standard-of-care treatment and were not going through extra invasive procedures."

IO biomarker • Preclinical • Oncology • Ovarian Cancer • Solid Tumor • FASLG • GZMB • IFNG

Randomised phase II study of ubamatamab ± cemiplimab in patients (pts) with platinum-resistant ovarian cancer (OC) (ESMO 2025) - P1/2 | "Med follow-up: 4.9 months. *Includes 1 partial response after data cutoff; † Includes 1 immune partial response (iRECIST); ‡ DOR not mature in ubamatamab 800 mg (now 3 pts responding >12 months) and ubamatamab 250 mg + cemiplimab arms."

Clinical • P2 data • Platinum resistant • Oncology • Ovarian Cancer • Solid Tumor • MUC16

Bispecific antibody Ubamatamab induces personalized anti-tumor immune responses in an ex vivo platform for ovarian cancer (AACR-NCI-EORTC 2025) - "Micro-tumors including the native TME were isolated from fresh ascites (n=12) or pleural fluid (n=2), seeded, and treated with pembrolizumab (single dose) and dose ranges of chemotherapeutics and ubamatamab (CD3xMUC16 bispecific T cell engager in Phase 1/2 clinical trials). This study demonstrates the classification and functional characterization of patient-specific sensitivity to ubamatamab, a bispecific T cell engager in clinical development for ovarian cancer. Our ex vivo 3D micro-tumor platform facilitates quantification of immune responses and the discovery of predictive biomarkers to support patient stratification for emerging immunotherapies."

IO biomarker • Preclinical • Oncology • Ovarian Cancer • Solid Tumor • CD8 • CXCL11 • CXCL9 • GZMB • IFNG • IL2

A PHASE 1/2 STUDY OF UBAMATAMAB (REGN4018) IN LOW-GRADE SEROUS OVARIAN CANCER COHORT (IGCS 2025) - P1/2 | "Prior to Q3W dosing of ubamatamab, patients will receive once-weekly step-up dosing to mitigate the risk of cytokine release syndrome, as well as sarilumab 350 mg IV prophylaxis on Day 1. Initial data analysis of the LGSOC-specific cohort is expected by March 2027. Insights gained from the efficacy and safety of ubamatamab in patients with LGSOC from this cohort may further validate MUC16 as a novel therapeutic target for LGSOC."

P1/2 data • Oncology • Ovarian Cancer • Ovarian Serous Adenocarcinoma • Solid Tumor • MUC16

Regeneron will also present data on Libtayo in lung cancer, ubamatamab for platinum-resistant ovarian cancer, and REGN7075, an EGFRxCD28 bispecific antibody, among other research findings. (Investing.com)

Clinical data • Platinum resistant • Non Small Cell Lung Cancer • Ovarian Cancer

A Study to Investigate Ubamatamab With and Without REGN7075 in Adult Participants With Advanced/Metastatic Non-Small Cell Lung Cancer (NSCLC) (clinicaltrials.gov) - P2 | N=300 | Not yet recruiting | Sponsor: Regeneron Pharmaceuticals

New P2 trial • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

R5668-ONC-1938: A Study to Find Out How Safe REGN5668 is and How Well it Works In Adult Women When Given With Either Cemiplimab, or Cemiplimab + Fianlimab, or Ubamatamab (clinicaltrials.gov) - P1/2 | N=612 | Recruiting | Sponsor: Regeneron Pharmaceuticals | Trial completion date: Apr 2027 ➔ Nov 2027

Trial completion date • Endometrial Cancer • Fallopian Tube Cancer • Oncology • Ovarian Cancer • Peritoneal Cancer • Solid Tumor

Mucin 16-Directed Therapy in Pediatric Sarcomas: Case Evidence of Ubamatamab Efficacy in Epithelioid Sarcoma and Its Implications for Other Sarcoma Subtypes. (PubMed, JCO Precis Oncol) - P2 | "MUC16 is frequently detected in ES and MRTs. Ubamatamab is an encouraging anti-MUC16 therapy, demonstrating clinical efficacy. Ongoing trials (ClinicalTrials.gov identifier: NCT06444880) are evaluating ubamatamab in other rare MUC16-positive tumors."

Journal • Retrospective data • Cardiovascular • Dermatology • Oncology • Ovarian Cancer • Pediatrics • Respiratory Diseases • Rhabdoid Tumor • Sarcoma • Soft Tissue Sarcoma • Solid Tumor • MUC16

R4018-ONC-1721: Study of REGN4018 (Ubamatamab) Administered Alone or in Combination With Cemiplimab in Adult Patients With Recurrent Ovarian Cancer or Other Recurrent Mucin-16 Expressing (MUC16+) Cancers (clinicaltrials.gov) - P1/2 | N=890 | Recruiting | Sponsor: Regeneron Pharmaceuticals | Trial completion date: Jun 2026 ➔ Jan 2027 | Trial primary completion date: Jun 2026 ➔ Feb 2026

Platinum resistant • Trial completion date • Trial primary completion date • Endometrial Cancer • Fallopian Tube Cancer • Oncology • Ovarian Cancer • Ovarian Serous Adenocarcinoma • Peritoneal Cancer • Solid Tumor

Investigation of Ubamatamab Combination Therapy in Adult Participants With Platinum-Resistant Ovarian Cancer (clinicaltrials.gov) - P2 | N=220 | Recruiting | Sponsor: Regeneron Pharmaceuticals | Not yet recruiting ➔ Recruiting

Enrollment open • Platinum resistant • Oncology • Ovarian Cancer • Solid Tumor

Investigation of Ubamatamab Combination Therapy in Adult Participants With Platinum-Resistant Ovarian Cancer (clinicaltrials.gov) - P2 | N=220 | Not yet recruiting | Sponsor: Regeneron Pharmaceuticals | Trial completion date: Apr 2028 ➔ Dec 2028 | Trial primary completion date: Apr 2028 ➔ Dec 2028

Platinum resistant • Trial completion date • Trial primary completion date • Oncology • Ovarian Cancer • Solid Tumor

Investigation of Ubamatamab Combination Therapy in Adult Participants With Platinum-Resistant Ovarian Cancer (clinicaltrials.gov) - P2 | N=220 | Not yet recruiting | Sponsor: Regeneron Pharmaceuticals

New P2 trial • Oncology • Ovarian Cancer • Solid Tumor

Translational findings support regimen selection for first-in-human study of ubamatamab (MUC16 × CD3 bispecific antibody) in patients with recurrent ovarian cancer. (PubMed, Clin Transl Sci) - "Integrating preclinical and clinical data determined a target trough concentration range of 5-30 mg/L, which supports evaluation of ubamatamab 250 mg with or without cemiplimab and 800 mg monotherapy once every 3 weeks in expansion cohorts. Preclinical data (cytokine release, tumor regression, monkey PK) had translational value in supporting regimen selection in dose escalation and subsequently in dose expansion after integration with patient data from dose escalation."

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

Phase II Trial of Ubamatamab Alone or in Combination With Cemiplimab in MUC16-Expressing SMARCB1-Deficient Malignancies (clinicaltrials.gov) - P2 | N=40 | Recruiting | Sponsor: M.D. Anderson Cancer Center | Not yet recruiting ➔ Recruiting

Combination therapy • Enrollment open • Oncology

Phase II Trial of Ubamatamab Alone or in Combination With Cemiplimab in MUC16-Expressing SMARCB1-Deficient Malignancies (clinicaltrials.gov) - P2 | N=40 | Not yet recruiting | Sponsor: M.D. Anderson Cancer Center | Trial primary completion date: Jul 2026 ➔ Jul 2028

Combination therapy • Trial primary completion date • Oncology

Ubamatamab, Anti-PD-1 ICI, May Bolster Immune Response in Kidney Cancer (Cancer Network) - "Ubamatamab in combination with anti-PD-inhibition may enhance the immune response in patients with MUC16-expressing SMARCB1-deficient renal medullary carcinoma and epithelioid sarcoma...Additionally, Msaouel outlined steps that will be undertaken in a phase 2 trial assessing the experimental therapy in patients with both cancer types. He said the trial will initially aim to evaluate the clinical effects of ubamatamab alone and follow up with a similar evaluation for ubamatamab in combination with an anti-PD-1 inhibitor, specifically cemiplimab (Libtayo)."

Clinical • Genito-urinary Cancer • Kidney Cancer • Renal Cell Carcinoma • Solid Tumor

Phase II Trial of Ubamatamab in MUC16-Expressing SMARCB1-Deficient Renal Medullary Carcinoma and Epithelioid Sarcoma (KCRS 2024) - "As proof of concept, a 20-year-old patient with metastatic SMARCB1-negative ES expressing high levels of serum CA125 achieved a durable (12+ months) partial response to ubamatamab after progressing on multiple prior therapies, including EZH2 inhibition with tazemetostat as well as antiPD1/CTLA4 immune checkpoint inhibition with nivolumab plus ipilimumab...Patients with disease progression on ubamatamab monotherapy during Stage I can proceed to stage II, which will evaluate the combination of ubamatamab with cemiplimab combination...Mucin 16 (cancer antigen 125) Expression in Epithelioid Sarcoma leads to Single-Patient Study with Bispecific T-Cell Engager Ubamatamab (Mucin16xCD3): A Bench-ToBedside Experience. Connective Tissue Oncology Society, Nov 16–19, 2022, Vancouver, Canada."

IO biomarker • P2 data • Cardiovascular • Kidney Medullary Carcinoma • Oncology • Ovarian Cancer • Renal Cell Carcinoma • Respiratory Diseases • Sarcoma • Soft Tissue Sarcoma • Solid Tumor • MUC16 • SMARCB1

Phase II Trial of Ubamatamab Alone or in Combination With Cemiplimab in MUC16-Expressing SMARCB1-Deficient Malignancies (clinicaltrials.gov) - P2 | N=40 | Not yet recruiting | Sponsor: M.D. Anderson Cancer Center

Combination therapy • New P2 trial • Oncology

A phase 1/2 study of ubamatamab (REGN4018), a MUC16×CD3 bispecific antibody, administered alone or in combination with cemiplimab (anti–PD-1) in patients with recurrent ovarian cancer or MUC16+ endometrial cancer. (ASCO 2024) - P1/2 | "Exploratory objectives include clinical correlation with serum CA-125, MUC16 IHC, and immune markers. The study is currently enrolling to these OC and EC expansion cohorts."

Clinical • Combination therapy • IO biomarker • P1/2 data • Endometrial Cancer • Oncology • Ovarian Cancer • Solid Tumor • MUC16

A phase I/II study of ubamatamab (REGN4018), a MUC16xCD3 bispecific antibody, administered alone or in combination with cemiplimab (anti-PD-1) in patients with recurrent ovarian cancer or MUC16+ endometrial cancer: Trial in progress update (SGO 2024) - P1/2 | "Exploratory endpoints include evaluation of baseline tumor MUC16 IHC expression and other biomarkers as predictors of response. The study is currently recruiting pts to the combination dose escalation, monotherapy dose expansion, and randomized Phase 2 cohorts."

Clinical • Combination therapy • IO biomarker • P1/2 data • Endometrial Cancer • Fallopian Tube Cancer • Oncology • Ovarian Cancer • Peritoneal Cancer • Solid Tumor • MUC16

Exposure-biomarker analyses for cytokine release syndrome or infusion-related reaction, pain, and cytokine concentrations in serum during treatment with ubamatamab, a MUC16xCD3 bispecific antibody, among patients with recurrent ovarian cancer (SGO 2024) - P1/2 | "Ubamatamab is currently being investigated in a first-in-human study (NCT03564340) to evaluate safety, pharmacokinetics, and efficacy in patients with recurrent ovarian cancer as monotherapy and in combination with cemiplimab. The findings indicate that the frequency and severity of acute events such as CRS/IRR, pain, or serum cytokine increase may be associated, at least in part, with ubamatamab Cmax after the initial dose in W1. A step-up dosing regimen of ubamatamab employed prior to full treatment doses limited these TEAEs, which ensured dose escalation up to 800 mg once weekly without reaching a maximum tolerated dose. The lack of exposure dependent increase in CRS/IRR at full-dose levels suggests a potential for desensitization when step-up dosing is utilized at appropriate intervals before a higher target dose level."

Biomarker • Clinical • Cytokine release syndrome • Oncology • Ovarian Cancer • Solid Tumor • IFNG • IL6 • MUC16

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

Study of REGN4018 Administered Alone or in Combination With Cemiplimab in Adult Patients With Recurrent Ovarian Cancer or Other Recurrent Mucin-16 Expressing (MUC16+) Cancers (clinicaltrials.gov) - P1/2 | N=690 | Recruiting | Sponsor: Regeneron Pharmaceuticals | Trial completion date: Jul 2024 ➔ Jun 2026 | Trial primary completion date: Jul 2024 ➔ Jun 2026

Trial completion date • Trial primary completion date • Endometrial Cancer • Fallopian Tube Cancer • Oncology • Ovarian Cancer • Peritoneal 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