A Phase 1/2 Study of REGN7075 (EGFRxCD28 Costimulatory Bispecific Antibody) in Combination with Cemiplimab in Patients with Advanced Solid Tumors

The primary objective of this study is to evaluate the **safety** and tolerability of a REGN7075 monotherapy lead-in and REGN7075 in combination with cemiplimab in patients with advanced solid tumors. This is clinically relevant as it aims to determine the potential adverse effects and the maximum tolerated dose of the investigational drug combination, which is crucial for ensuring patient safety and guiding future therapeutic strategies.

Secondary objectives include:

• Characterizing the pharmacokinetics (PK) of REGN7075 alone and in combination with cemiplimab.
• Assessing the preliminary efficacy of REGN7075 in combination with cemiplimab, as measured by objective response rate (ORR), overall survival (OS), progression-free survival (PFS), duration of response (DOR), complete response (CR) rate, and disease control rate (DCR) per RECIST 1.1 and/or composite response criteria.
• Evaluating the immunogenicity of REGN7075 and cemiplimab.
• Assessing the safety and tolerability of REGN7075 in combination with cemiplimab with or without chemotherapy.
• Characterizing the PK of REGN7075 in combination with cemiplimab with or without chemotherapy.
• Evaluating the effect of REGN7075 alone and in combination with cemiplimab with or without chemotherapy on patient-reported outcomes, including health-related quality of life (HRQoL), as measured by validated instruments such as the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) and others specific to cancer types.

The clinical trial involves a total of **415 participants** diagnosed with **solid tumors**. The study population includes both male and female subjects, with an age range that encompasses adults and older adults. Participants were selected based on specific criteria, including an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, and a histologically or cytologically confirmed cancer. The trial also includes individuals who are anti-programmed cell death protein-1 (PD-1)/programmed cell death ligand-1 (PDL1) naïve. Participants are required to have at least one lesion that meets study criteria and must be willing to provide tumor tissue from a newly obtained biopsy. Adequate organ and bone marrow function, as well as a life expectancy of at least three months, are also necessary for inclusion. The trial population includes vulnerable groups, and lifestyle factors such as diet and physical activity are not specified in the available data.

The clinical trial is designed to evaluate the safety, tolerability, and preliminary efficacy of **REGN7075** in combination with **cemiplimab** in patients with advanced solid tumors. This study is structured as a Phase 1/2 trial, incorporating a **randomized**, **double-blind**, and **controlled** design. The trial is expected to commence on November 1, 2023, and conclude by December 12, 2026, with the primary objective of assessing dose escalation and expansion phases. The trial will involve a series of study visits, beginning with an inclusion (screening) visit to determine eligibility based on criteria such as an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, confirmed cancer diagnosis, and adequate organ function. Participants will be required to provide tumor tissue from a newly obtained biopsy.

Following the screening, participants will undergo a series of follow-up visits to monitor the incidence of dose-limiting toxicities (DLTs), treatment-emergent adverse events (TEAEs), and other safety parameters. The primary endpoints include the incidence and severity of adverse events, while secondary endpoints focus on pharmacokinetics, progression-free survival, and overall survival. The end-of-study visit will assess the overall response rate and disease control rate. Participant involvement is expected to last until the end of the trial, with conditions for early termination including significant adverse events or withdrawal of consent. The trial aims to provide comprehensive data on the efficacy and safety of the investigational combination therapy in a controlled clinical setting.

The clinical trial involves the administration of **REGN7075**, a **powder for solution for injection**. This investigational medication is administered subcutaneously. The specific dosage and frequency of administration are determined based on the study protocol, with careful monitoring of participant compliance. REGN7075 is a protein-based substance developed by Regeneron Pharmaceuticals, Inc., and is not a pediatric formulation.

**LIBTAYO** (cemiplimab) is used as a comparator treatment in the trial. It is provided as a **350 mg concentrate for solution for infusion** and is administered via infusion. The administration schedule is aligned with the study's design to evaluate its efficacy in combination with REGN7075. LIBTAYO is a monoclonal antibody produced by Regeneron Ireland D.A.C.

**Lonsurf**, containing **trifluridine** and **tipiracil hydrochloride**, is included as a non-experimental treatment. It is available in **film-coated tablets** with dosages of 15 mg/6.14 mg and 20 mg/8.19 mg. The tablets are administered orally, following a dosing schedule that supports the trial's objectives. Lonsurf is manufactured by Les Laboratoires Servier (Suresnes).

**Avastin** (bevacizumab) is another non-experimental treatment used in the study. It is a **25 mg/ml concentrate for solution for infusion** and is administered intravenously. Avastin is a monoclonal antibody provided by Roche Registration GmbH, and its administration is conducted according to the trial's protocol.

**Pemetrexed** is included in the trial as a **solution for infusion**. It is available in two formulations: Pemetrexed Fresenius Kabi and Pemetrexed EVER Pharma, both at a concentration of 25 mg/ml. These are administered intravenously, with dosing schedules tailored to the study's requirements. Pemetrexed is a chemical-based medication.

**Cisplatin** is administered as a **solution for infusion** at a concentration of 1 mg/ml. This chemical-based treatment is provided by Accord Healthcare Polska Sp. z o.o. and is used in the trial to assess its effects in combination with other treatments.

**Carboplatin** is also used in the study as a **solution for infusion**. It is provided by Hikma Farmacêutica (Portugal), S.A., and is administered according to the trial's protocol to evaluate its role in the treatment regimen.

**Paclitaxel** is included as a **solution for infusion** at a concentration of 6 mg/ml. This chemical-based treatment is provided by AqVida GmbH and is administered intravenously, following the study's dosing schedule.

The efficacy of the clinical trial will be assessed through a series of primary and secondary endpoints. The primary endpoints include the **Objective Response Rate (ORR)** during the dose expansion phase, which will be evaluated using the Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) and/or composite response criteria. The secondary endpoints encompass a range of measures, including the concentrations of REGN7075 in serum, **Progression Free Survival (PFS)**, **Duration of Response (DOR)**, **Disease Control Rate (DCR)**, **Complete Response (CR) rate**, and **Overall Survival (OS)**. Additionally, the incidence and titers of anti-drug antibodies (ADA) to REGN7075 and cemiplimab will be monitored.

Patient-reported outcomes will also be considered, focusing on quality of life, symptoms, functioning, and general health status, as measured by validated instruments such as the EORTC QLQ-C30 and EQ-5D-5L, among others specific to cancer types. The incidence and severity of treatment-emergent adverse events (TEAEs), adverse events of special interest (AESIs), serious adverse events (SAEs), and grade ≥3 laboratory abnormalities will be documented. These assessments will be conducted at specified intervals throughout the trial to ensure comprehensive data collection and analysis.