Cancer, Neoplasm
Conditions
Brief summary
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.
Detailed description
Estimated Study Duration: Dose Escalation (Part 1): Approximately 34 months Dose Optimization/Expansion (Part 2): Approximately 28 months
Interventions
DRUGSAR444881
Pharmaceutical form: Solution for infusion; Route of administration: Intravenous
DRUGPembrolizumab
Pharmaceutical form: Solution for infusion; Route of administration: Intravenous
DRUGCetuximab
Pharmaceutical form: Solution for infusion; Route of administration: Intravenous
DRUGCarboplatin
Pharmaceutical form: Concentrate for solution for infusion; Route of administration: Intravenous
DRUGPemetrexed
Pharmaceutical form: Powder for concentrate for solution for infusion or concentrate for solution for infusion; Route of administration: Intravenous
Sponsors
Sanofi
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part 1: Incidence of treatment-emergent adverse events (TEAEs) dose limiting toxicities (DLT) | Cycle 1 (28 days) | Incidence of TEAEs meeting protocol defined DLT criteria |
| Part 1: Incidence of treatment-emergent adverse events and serious adverse events | Through study completion, an average of 5 months | — |
| Part 2: Objective Response Rate (ORR) per RECIST v1.1 | Through study completion, an average of 3 months | Proportion of participants with a best overall response of complete response (CR) or partial response (PR) per RECIST v1.1 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Part 2: Incidence of ADA | Through study completion, an average of 6 months | — |
| Part 2: Ctrough | Through study completion, an average of 3 months | — |
| Part 1: Objective Response Rate (ORR) per RECIST v1.1 | Through study completion, an average of 3 months | Proportion of participants with a best overall response of complete response (CR) or partial response (PR) per RECIST v1.1 |
| Part 1: Maximum observed plasma concentration [Cmax] | Through study completion, an average of 2 months | — |
| Part 1: Serum concentration at the end of the dosing interval (Ctrough) | Through study completion, an average of 2 months | — |
| Part 1: time of maximum observed serum concentration (Tmax) | Through study completion, an average of 2 months | — |
| Part 1: Terminal elimination half-life [T1/2] | Through study completion, an average of 2 months | — |
| Part 2: Tmax | Through study completion, an average of 3 months | — |
| Part 1: Incidence of anti-drug antibodies (ADA) | Through study completion, an average of 5 months | — |
| Part 2: Progression Free Survival (PFS) | Up to 24 months | Time from the date of first dose of study drug to the date of first documented disease progression or death due to any cause, whichever occurs first. |
| PFS rate | At 3, 6, 9, and 12 months, and up to 24 months | Percentage of participants with PFS, per RECIST v1.1 |
| Part 2: Duration of Response | Through study completion, an average of 6 months | Duration between first documentation of CR or PR to first documentation of disease progression or death due to any cause, whichever occurs first |
| Part 2: Incidence of treatment-emergent adverse events and Serious Adverse Events | Through study completion, an average of 6 months | — |
| Part 2: Cmax | Through study completion, an average of 3 months | — |
| Part 1: Area under the plasma concentration-time curve [AUC] | Through study completion, an average of 2 months | — |
| Part 2: T1/2 | Through study completion, an average of 3 months | — |
| Part 2: AUC | Through study completion, an average of 3 months | — |
Countries
Canada, Israel, United Kingdom, United States
Outcome results
None listed