marlotamig (REGN7075) / Regeneron - LARVOL DELTA

A Phase 1/2 study of REGN7075 (EGFRxCD28 costimulatory bispecific antibody) in combination with cemiplimab (anti-PD-1) in patients with advanced solid tumors: Initial dose-escalation results (SITC 2022) - P1/2 | "Biomarker studies are ongoing. Clinical trial enrollment is ongoing; we are currently evaluating the 100mg cohort."

Clinical • Combination therapy • IO biomarker • P1/2 data • Cervical Cancer • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • CD28 • EGFR

A phase 1/2 study of REGN7075 in combination with cemiplimab (cemi) in patients (pts) with advanced solid tumors: Efficacy and safety results. (ASCO 2024) - P1/2 | "MSS CRC is historically unresponsive to immunotherapy. REGN7075 is one of the first immune therapies to demonstrate clinical activity in pts with MSS CRC (including a pt with liver metastases), and dose escalation was completed through 900 mg with an acceptable safety profile and no DLTs. One pt experienced Grade 1 CRS, demonstrating differentiation from CD28 superagonists and CD3-targeting bsAbs."

Clinical • Combination therapy • IO biomarker • Metastases • P1/2 data • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • CD28 • EGFR • IFNG

NSABP FC-13 (EMPIRE): A phase II platform study of cemiplimab monotherapy or cemiplimab-based combinations in patients with colorectal cancer and minimal residual disease (MRD) after definitive therapy. (ASCO-GI 2026) - P2 | " This multicenter Phase II platform study randomizes patients with MSS stage II–III or oligometastatic stage IV CRC who are ctDNA-positive within 12 weeks of completing definitive therapy (surgery ± chemotherapy/chemoradiotherapy) to one of three arms: 1) Cemiplimab 350 mg IV q3w × 1 year; 2) Cemiplimab 350 mg + fianlimab 1600 mg IV q3w × 1 year; and 3) Cemiplimab 350 mg + REGN7075 2700 mg IV q3w × 1 year. Statistical design: Arm 1 follows a Simon two-stage design with up to 33 patients (α=0.047, power=0.80), and Arms 2 & 3 enroll up to 23 patients each (single-stage; α=0.05, power=0.78). Status: Enrollment began in September 2025 across NSABP Foundation sites and is ongoing."

Clinical • IO biomarker • Minimal residual disease • Monotherapy • P2 data • Residual disease • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor

A Study of Cemiplimab Plus Chemotherapy Versus Cemiplimab Plus Chemotherapy Plus Other Cancer Treatments for Adult Patients With Operable Non-Small Cell Lung Cancer (NSCLC) (clinicaltrials.gov) - P2 | N=120 | Active, not recruiting | Sponsor: Regeneron Pharmaceuticals | Recruiting ➔ Active, not recruiting

Enrollment closed • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

COMBINE-EGFR-1: A Trial to Find Out How Safe REGN7075 is and How Well it Works in Combination With Cemiplimab for Adult Participants With Advanced Cancers (clinicaltrials.gov) - P1/2 | N=548 | Active, not recruiting | Sponsor: Regeneron Pharmaceuticals | Recruiting ➔ Active, not recruiting | N=933 ➔ 548

Enrollment change • Enrollment closed • Colorectal Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma of Head and Neck • Squamous Cell Skin Cancer • Triple Negative Breast Cancer

Capecitabine/Oxaliplatin Chemotherapy and Cemiplimab With or Without Fianlimab or REGN7075 in Locally Advanced Rectal Cancer (clinicaltrials.gov) - P2 | N=66 | Recruiting | Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Not yet recruiting ➔ Recruiting

Enrollment open • Colorectal Cancer • Oncology • Rectal Adenocarcinoma • Rectal Cancer • Solid Tumor

EMPIRE (NSABP FC-13): a biomarker-driven phase II platform trial evaluating cemiplimab-based immunotherapy in microsatellite-stable colorectal cancer with ctDNA-defined minimal residual disease. (PubMed, Future Oncol) - P2 | "Eligible patients have postoperative ctDNA positivity in the absence of radiographic recurrence and are allocated to one of three treatment arms: cemiplimab monotherapy; cemiplimab plus fianlimab (a lymphocyte activation gene-3 inhibitor); or cemiplimab plus REGN7075 (an EGFR×CD28 costimulatory bispecific antibody). Arms 2 and 3 use single-stage phase II designs, whereas Arm 1 follows a Simon two-stage design with early futility stopping. The study integrates comprehensive correlative analyses to characterize mechanisms of response and resistance.Clinical trial registration: The http://www.clinicaltrials.gov identifier is NCT07058012."

Biomarker • Circulating tumor DNA • IO biomarker • Journal • Minimal residual disease • P2 data • Colorectal Cancer • Oncology • Solid Tumor • EGFR • LAG3

NSABP FC-13 (EMPIRE): A phase II platform study of cemiplimab monotherapy or cemiplimab-based combinations in patients with colorectal cancer and minimal residual disease (MRD) after definitive therapy. (ASCO 2026) - P2 | " This multicenter Phase II platform study randomizes patients with MSS stage II–III or oligometastatic stage IV CRC who are ctDNA-positive within 12 weeks of completing definitive therapy (surgery ± chemotherapy/chemoradiotherapy) to one of three arms: (1) Cemiplimab 350 mg IV q3w × 1 year; (2) Cemiplimab 350 mg + fianlimab 1600 mg IV q3w × 1 year; (3) Cemiplimab 350 mg + REGN7075 2700 mg IV q3w × 1 year. Status: Enrollment began in September 2025 across NSABP Foundation sites and is ongoing. Clinical trial registration: NCT07058012."

Clinical • IO biomarker • Minimal residual disease • Monotherapy • P2 data • Residual disease • Colorectal Cancer • Oncology • Solid Tumor

A Phase II Platform Study to Evaluate Treatment With Cemiplimab Monotherapy or Cemiplimab Plus Fianlimab or Other Novel Combinations in Patients With Colorectal Cancer With Minimal Residual Disease Following Definitive Surgery and Chemotherapy (EMPIRE) (clinicaltrials.gov) - P2 | N=79 | Recruiting | Sponsor: NSABP Foundation Inc | Trial primary completion date: Jun 2028 ➔ Apr 2029 | Not yet recruiting ➔ Recruiting

Enrollment open • Minimal residual disease • Monotherapy • Trial primary completion date • Colon Cancer • Colorectal Cancer • Oncology • Solid Tumor

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 | Recruiting | Sponsor: Regeneron Pharmaceuticals | Not yet recruiting ➔ Recruiting

Enrollment open • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • MUC16

COMBINE-EGFR-1: A Trial to Find Out How Safe REGN7075 is and How Well it Works in Combination With Cemiplimab for Adult Participants With Advanced Cancers (clinicaltrials.gov) - P1/2 | N=933 | Recruiting | Sponsor: Regeneron Pharmaceuticals | Trial completion date: Dec 2026 ➔ Apr 2027

Trial completion date • Colorectal Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma of Head and Neck • Squamous Cell Skin Cancer • Triple Negative Breast Cancer

Capecitabine/Oxaliplatin Chemotherapy and Cemiplimab With or Without Fianlimab or REGN7075 in Locally Advanced Rectal Cancer (clinicaltrials.gov) - P2 | N=66 | Not yet recruiting | Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

New P2 trial • Colorectal Cancer • Oncology • Rectal Cancer • Solid Tumor

Mitigating infusion-related reactions (IRRs) with cetirizine and montelukast in patients (pts) receiving REGN7075, an EGFR×CD28 bispecific antibody (bsAb) (ESMO 2025) - P1/2 | "An ongoing first-in-human, open label, phase 1/2 study (NCT04626635) is evaluating REGN7075 ± cemiplimab (anti–programmed cell death-1) in pts with advanced solid tumours. Hypotension as a symptom of IRRs occurred in 36% of pts in the SP cohort versus 6% in the SP + CM cohort. Conclusions The addition of CM prior to the first two doses of REGN7075 led to a reduction in the incidence and severity of IRRs."

Clinical • Oncology • Solid Tumor • CD28 • EGFR

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

A Phase II Platform Study to Evaluate Treatment With Cemiplimab Monotherapy or Cemiplimab Plus Fianlimab or Other Novel Combinations in Patients With Colorectal Cancer With Minimal Residual Disease Following Definitive Surgery and Chemotherapy (EMPIRE) (clinicaltrials.gov) - P2 | N=79 | Not yet recruiting | Sponsor: NSABP Foundation Inc

Minimal residual disease • Monotherapy • New P2 trial • Colorectal Cancer • Oncology • Solid Tumor

A randomized study of neoadjuvant REGN7075 + cemiplimab + chemotherapy (chemo) vs cemiplimab + chemo in patients (pts) with resectable non-small cell lung cancer (NSCLC). (ASCO 2025) - P1/2, P2 | "A Bayesian statistical design will be used to evaluate the posterior probability of at least 15% improvement in MPR for investigational arms vs the control arm. This study is currently enrolling."

Clinical • IO biomarker • Colorectal Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • CD28 • EGFR • PD-L1

Regeneron to Highlight Advances at ASCO with Phase 3 Adjuvant Libtayo (cemiplimab) CSCC Updates and Promising Early Blood Cancer Data with Linvoseltamab Combination (GlobeNewswire) - "Eighteen presentations will share the latest insights from ongoing research of approved and investigational treatment regimens across a range of difficult-to-treat cancers including non-melanoma and melanoma skin cancer, lung cancer, lymphoma and multiple myeloma...Notable presentations at ASCO on Regeneron’s oncology pipeline include detailed efficacy and safety findings from the Phase 3 C-POST trial evaluating the adjuvant use of the PD-1 inhibitor Libtayo in post-surgical high-risk cutaneous squamous cell carcinoma (CSCC). The results will be presented in an oral session on Saturday, May 31...Regeneron will debut results from two cohorts of the LINKER-MM2 trial...which will be featured in two rapid oral presentations on Monday, June 2...In addition, the results of a cooperative group study reporting on the primary analysis of a randomized Phase 2 trial of vidutolimod..."

Clinical data • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Lymphoma • Melanoma • Multiple Myeloma • Non Small Cell Lung Cancer • Non-melanoma Skin Cancer • Squamous Cell Carcinoma of Head and Neck • Squamous Cell Skin Cancer

A Study of Cemiplimab Plus Chemotherapy Versus Cemiplimab Plus Chemotherapy Plus Other Cancer Treatments for Adult Patients With Operable Non-Small Cell Lung Cancer (NSCLC) (clinicaltrials.gov) - P2 | N=120 | Recruiting | Sponsor: Regeneron Pharmaceuticals | Not yet recruiting ➔ Recruiting

Enrollment open • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

A Phase 1/2 Study of REGN7075 (EGFRÃ-CD28) Combined with Cemiplimab (anti-PD-1) In NSCLC: Trial in Progress Update (IASLC-WCLC 2024) - P1/2 | "As of February 23, 2024, 122 patients were enrolled in Part 1. The study is ongoing and open to enrollment."

IO biomarker • P1/2 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • CD28 • EGFR • MET • PD-L1 • ROS1

A Study of Cemiplimab Plus Chemotherapy Versus Cemiplimab Plus Chemotherapy Plus Other Cancer Treatments for Adult Patients With Operable Non-Small Cell Lung Cancer (NSCLC) (clinicaltrials.gov) - P2 | N=120 | Not yet recruiting | Sponsor: Regeneron Pharmaceuticals

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

Promising Anti-tumor Activity of Novel Costimulatory Bispecific Antibody REGN7075 (EGFRxCD28) in Combination with Libtayo (cemiplimab) to be Reported at ASCO (GlobeNewswire) - P1/2 | N=769 | COMBINE-EGFR-1 (NCT04626635) | Sponsor: Regeneron Pharmaceuticals | "Among 94 patients treated as of data cutoff, 65% (n=61) had MSS CRC, of which 51 MSS CRC patients were treated at an active dose level. Efficacy results among these 51 patients were as follows...6% (n=3) overall response rate (ORR) and 29% (n=15) disease control rate (DCR). This included one complete response (CR), two partial responses (PR), and 12 patients with stable disease; Among the subset of 15 patients without liver metastases, there was a 20% ORR (n=3) and 80% DCR (n=12)...REGN7075 and Libtayo showed an acceptable safety profile, and the maximum tolerated dose was not reached...Grade 3 and 4 TEAEs occurred in 35% of patients...While the dose escalation portion of the trial across multiple solid tumor types including non-small cell lung cancer, colorectal cancer, head and neck cancer and other tumor types is ongoing, expansion cohorts in several tumor types have also been initiated."

P1/2 data • Colorectal Cancer • Head and Neck Cancer • Non Small Cell Lung Cancer

Regeneron to Showcase Progress in Advancing Novel Investigational Treatment Approaches for a Broad Range of Solid Tumors and Blood Cancers at ASCO (GlobeNewswire) - "Notably, new safety and efficacy results from a Phase 1/2 trial investigating the costimulatory bispecific antibody REGN7075 (EGFRxCD28) in combination with Libtayo in patients with certain advanced solid tumors will be featured in an oral presentation....Among them are presentations on updated data and new analyses for linvoseltamab (BCMAxCD3) in multiple myeloma; odronextamab (CD20xCD3) in several lymphoma subtypes; REGN6569 (GITR) in combination with Libtayo across solid tumors; and fianlimab (LAG-3 inhibitor) in combination with Libtayo in non-small cell lung cancer, melanoma and head and neck cancer."

Clinical data • P1/2 data • Head and Neck Cancer • Lung Cancer • Lymphoma • Melanoma • Multiple Myeloma • Non Small Cell Lung Cancer • Solid Tumor

A phase 1/2 study of REGN7075 (EGFRxCD28 costimulatory bispecific antibody) in combination with cemiplimab (anti–PD-1) in patients with advanced solid tumors, including colorectal cancer: Trial in progress update. (ASCO-GI 2024) - P1/2 | "This study is ongoing and currently open to enrollment. Clinical trial information: NCT04626635."

Clinical • Combination therapy • Metastases • P1/2 data • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • CD28

A Trial to Find Out How Safe REGN7075 is and How Well it Works in Combination With Cemiplimab for Adult Participants With Advanced Cancers (clinicaltrials.gov) - P1/2 | N=769 | Recruiting | Sponsor: Regeneron Pharmaceuticals | N=434 ➔ 769 | Trial completion date: Apr 2026 ➔ Dec 2026 | Trial primary completion date: Apr 2026 ➔ Aug 2026

Combination therapy • Enrollment change • Metastases • Trial completion date • Trial primary completion date • Colorectal Cancer • Gastrointestinal Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma of Head and Neck • Squamous Cell Skin Cancer • Triple Negative Breast Cancer