Study of SAR444881 Administered Alone and in Combination With Other Therapeutics in Participants With Advanced Solid Tumors

Sanofi

Status and phase: Terminated; Phase 2; Phase 1

Conditions: Neoplasm; Cancer

Treatments: Drug: Cetuximab; Drug: SAR444881; Drug: Pemetrexed; Drug: Pembrolizumab; Drug: Carboplatin

Study type: Interventional

Funder types: Industry

Identifiers

NCT04717375

BND-22-001

2023-504937-30-00 (Registry Identifier)

TCD17465

U1111-1277-4421 (Other Identifier)

Details and patient eligibility

About

The study will enroll advanced cancer patients with unresectable or metastatic disease who are refractory to or are not candidates for standard approved therapy. The study will be comprised of two parts - a dose escalation phase (Part 1) and a dose optimization/expansion phase (Part 2). Part 1 is comprised of three sub-parts: SAR444881 administered alone (Sub-Part 1A), SAR444881 administered in combination with pembrolizumab (Sub-Part 1B), and SAR444881 administered in combination with cetuximab (Sub-Part 1C). Part 2 is composed of two sub-parts: a dose optimization part where up to two doses of SAR444881 per indication are administered in combination with pembrolizumab, cetuximab, and/or carboplatin and pemetrexed (Sub-Part 2A); and a dose expansion part where SAR444881 is administered alone (Sub-Part 2B). In Sub-Part 2A, a two-stage design will be implemented to conduct dose optimization for each indication with combination therapy- Stage 1 (Preliminary Assessment) and Stage 2 (Randomization). Study is non-randomized except Stage 2 of Sub-Part 2A which will use randomization.

Full description

Estimated Study Duration:

Dose Escalation (Part 1): Approximately 34 months Dose Optimization/Expansion (Part 2): Approximately 28 months

Enrollment: 125 patients

Sex: All

Ages: 18+ years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

• Patients with unresectable or metastatic disease who are refractory to or are not candidates for standard approved therapy
• Histologic confirmation of malignancy
• Measurable disease per RECIST v1.1
• Eastern Cooperative Oncology Group Performance Status (ECOG) of 0 or 1
• Participants must have adequate organ function as defined by laboratory tests
• Part 1: Following tumor types: Breast cancer, cervical cancer, colorectal cancer, adenocarcinoma or squamous cell carcinoma of the esophagus, gastric or gastroesophageal junction adenocarcinoma, squamous cell carcinoma of the head and neck, hepatobiliary cancers (hepatocellular carcinoma (HCC), gallbladder cancer, cholangiocarcinoma), non-small cell lung cancer, renal cell carcinoma, squamous cell carcinoma of the skin, pancreatic adenocarcinoma, ovarian cancer or urothelial carcinoma
• Part 2: Following tumor types: Squamous cell carcinoma of the head and neck, Gastric or gastroesophageal junction adenocarcinoma, non-squamous non-small cell lung cancer, non-small cell lung cancer, colorectal carcinoma (CRC) any RAS, and/or Cholangiocarcinoma

Exclusion criteria

• Active, known or suspected autoimmune disease
• Condition requiring systemic treatment with either corticosteroids or other immunosuppressive medications
• Brain or leptomeningeal metastases
• Known history of positive test for HIV
• Non-HCC patients: acute or chronic hepatitis B virus (HBV) or hepatitis C virus (HCV); HCC patients: untreated active HBV or dual infection with HBV/HCV
• Participants after solid organ or allogeneic hematopoietic stem cell transplant
• History of life-threatening toxicity related to prior immune therapy
• History of life-threatening toxicity related to prior cetuximab or other anti-EGFR antibodies (for Sub-Part 1C)
• Unstable or deteriorating cardiovascular disease within the previous 6 months
• Any major surgery within 4 weeks of study drug administration
• Prior/Concomitant Therapy:
• Cytotoxic/Non-cytotoxic anti-cancer agents, unless at least 4 weeks have elapsed from last dose
• Use of other investigational drugs within 28 days
• Prior treatment with macrophage or natural killer (NK) cells activating therapies
• Administration of a live attenuated vaccine within 28 days

The above information is not intended to contain all considerations relevant to the potential participation in a clinical trial.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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125 participants in 5 patient groups

SAR444881 Dose Escalation (Sub-Part 1A)

Experimental group

Description:

Standard "3 + 3" dose escalation design with enrollment of at least 3 participants per dose level cohort. SAR444881 will be administered intravenously (IV), every 2 weeks (Q2W).

Treatment:

Drug: SAR444881

SAR444881 in Combination with Pembrolizumab Dose Escalation (Sub-Part 1B)

Experimental group

Description:

Standard "3 + 3" dose escalation design with enrollment of at least 3 participants per dose level cohort. SAR444881 and pembrolizumab will be administered intravenously (IV), every 3 weeks (Q3W).

Treatment:

Drug: Pembrolizumab

Drug: SAR444881

SAR444881 in Combination with Cetuximab Dose Escalation (Sub-Part 1C)

Experimental group

Description:

Standard "3 + 3" dose escalation design with enrollment of at least 3 participants per dose level cohort. SAR444881 and cetuximab will be administered intravenously (IV), every 2 weeks (Q2W).

Treatment:

Drug: SAR444881

Drug: Cetuximab

SAR444881 Dose Optimization (Sub-Part 2A)

Experimental group

Description:

SAR444881 Dose Optimization in combination with pembrolizumab/carboplatin/pemetrexed, pembrolizumab, or cetuximab. The indication for the combination cohorts will be non-squamous non-small cell lung cancer (NSCLC), gastric cancer or gastro-esophageal junction adenocarcinoma (GC/GEJ), colorectal carcinoma (CRC) any RAS. Enrollment will start after the recommended dose(s) of SAR444881 have been determined based on data from Sub-Parts 1A, 1B, and 1C.

Treatment:

Drug: Carboplatin

Drug: Pembrolizumab

Drug: Pemetrexed

Drug: SAR444881

Drug: Cetuximab

SAR444881 Dose Expansion (Sub-Part 2B)

Experimental group

Description:

The indication for this monotherapy cohort is cholangiocarcinoma. Enrollment will be opened based on emerging data from the dose-escalation phase and combination optimization data.

Treatment:

Drug: SAR444881