What side effects are associated with this type of intervention?

Common treatments for liver cancer, such as pembrolizumab (an anti-PD1 antibody) and cetuximab (an anti-EGFR antibody), have known side effects. Pembrolizumab can cause immune-related adverse events including fatigue, rash, diarrhea, and more severe conditions like pneumonitis, colitis, hepatitis, endocrinopathies, and nephritis. Cetuximab often leads to skin reactions (acneiform rash), hypomagnesemia, infusion reactions, and gastrointestinal issues like diarrhea. When combined with SAR444245, a non-alpha-IL2 modulating immune response, these treatments may result in overlapping toxicities, particularly immune-related adverse events.

What prior FDA approvals exist?

For the treatment of liver cancer, the FDA has approved several immunotherapy and targeted therapy drugs. Sorafenib (Nexavar) was one of the first targeted therapies approved, inhibiting RAF kinase and VEGFR. More recently, immune checkpoint inhibitors like nivolumab (Opdivo) and pembrolizumab (Keytruda) have been approved for advanced hepatocellular carcinoma (HCC) after prior sorafenib treatment. These drugs enhance T-cell activity by targeting PD-1. While cetuximab (an anti-EGFR antibody) is not specifically approved for liver cancer, it is used in other cancers to inhibit cancer cell growth. The combination of immune modulators and checkpoint inhibitors, similar to SAR444245 with pembrolizumab, represents a promising area of ongoing research.

What other types of research exist?

Promising novel alternatives for liver cancer treatment in 2024 include: 1) CD137 agonist antibodies, which have shown potent antitumor activity with reduced liver toxicity. 2) TCR mimic antibodies targeting specific cancer epitopes, such as alpha-fetoprotein peptide presented by HLA-A*02, which have demonstrated specificity and safety in hepatocellular carcinoma. 3) Combination therapies involving immune checkpoint inhibitors like Nivolumab (anti-PD1) with Ipilimumab (anti-CTLA-4), which have shown encouraging antitumor activity in various cancers.

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EGFR Inhibitor

SAR444245 + Anticancer Therapies for Gastrointestinal Cancer

Q: What is the mechanism of action of this treatment?

Common treatments for liver cancer include immune checkpoint inhibitors like pembrolizumab, which enhance T-cell activity by blocking the PD-1 pathway, allowing the immune system to better attack cancer cells. Another approach involves targeted antibodies such as cetuximab, which inhibits the epidermal growth factor receptor (EGFR) on cancer cells, thereby preventing their growth and proliferation. The combination of these therapies with agents like SAR444245, a non-alpha-IL2 modulator, aims to further boost the immune response against cancer cells. These mechanisms are crucial for liver cancer patients as they offer a way to target the cancer more precisely and potentially improve treatment outcomes by leveraging the body's own immune system.

Phase 2

Waitlist Available

Research Sponsored by Sanofi

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Participant must be ≥18 years of age (or country's legal age of majority if >18 years), at the time of signing the informed consent

Participants with histologically or cytologically confirmed diagnosis of advanced unresectable or metastatic GC or Siewert Type 2 & 3 GEJ

Must not have

Active, known, or suspected autoimmune disease that has required systemic treatment in the past 2 years

Receipt of a live-virus or live attenuated-virus vaccination within 28 days of planned treatment start. Seasonal flu vaccines that do not contain live virus are permitted

Timeline

Screening 3 weeks

Treatment Varies

Follow Up day 1 of cycle 1-2-3-4-6-8-10 + every 4th cycle (each cycle is 21 days), maximum up to approximately 24 months

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing a new drug called SAR444245 in combination with other cancer treatments for adults with advanced gastrointestinal cancers. The goal is to boost the immune system to better fight cancer cells.

Who is the study for?

Adults with advanced gastrointestinal cancers, including esophageal squamous cell carcinoma, gastric cancer or gastro-esophageal junction adenocarcinoma, hepatocellular carcinoma (HCC), and metastatic colorectal cancer (non-MSI-H). Participants must have measurable lesions and agree to contraception. Excluded are those with poor performance status, organ function issues, brain metastases, recent major surgery or therapy, autoimmune diseases requiring treatment in the past 2 years.

What is being tested?

The trial is testing SAR444245 (THOR-707) combined with pembrolizumab or cetuximab in various cohorts of gastrointestinal cancer patients. It aims to see if these combinations can increase the percentage of patients who respond to treatment. The study involves multiple sub-studies targeting different types of tumors.

What are the potential side effects?

Potential side effects may include immune-related reactions due to pembrolizumab or cetuximab such as inflammation in organs; infusion reactions; fatigue; skin rash; digestive issues like diarrhea; liver enzyme elevation could occur from THOR-707.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I am at least 18 years old or the legal age in my country.

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My cancer is advanced, cannot be surgically removed, and is in the stomach or gastroesophageal junction.

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My colorectal cancer is advanced, cannot be surgically removed, and is not MSI-H.

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My liver cancer is advanced and cannot be removed by surgery.

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My esophageal cancer is advanced, cannot be surgically removed, and is a type called squamous cell.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I have an autoimmune disease treated in the last 2 years.

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I have not received a live-virus vaccine in the last 28 days.

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I haven't taken antibiotics (except creams or ointments) in the last 14 days.

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I need assistance with daily activities due to my health condition.

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I have had an organ transplant or received donor tissue.

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I have active cancer spread to my brain or its coverings.

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I have previously received IL2-based cancer treatment.

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I have been treated with drugs that target PD-1/PD-L1 before.

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I haven't had cancer treatment or major surgery in the last 28 days.

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I've been on more than 10 mg of prednisone or similar daily in the last 2 weeks.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ day 1 of cycle 1-2-3-4-6-8-10 + every 4th cycle (each cycle is 21 days), maximum up to approximately 24 months

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~day 1 of cycle 1-2-3-4-6-8-10 + every 4th cycle (each cycle is 21 days), maximum up to approximately 24 months

This trial's timeline: 3 weeks for screening, Varies for treatment, and day 1 of cycle 1-2-3-4-6-8-10 + every 4th cycle (each cycle is 21 days), maximum up to approximately 24 months for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Objective Response Rate (ORR)

Secondary study objectives

Assessment of SAR444245 safety profile when combined with other anti-cancer therapies-Serious Adverse Events (SAEs)

Assessment of SAR444245 safety profile when combined with other anti-cancer therapies-Treatment-emergency adverse events (TEAEs)

Clinical benefit rate

+4 more

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

7Treatment groups

Experimental Treatment

Group I: Cohort D2 (Sub-study 04): 3-6L CRC non-MSI-H RAS wild typeExperimental Treatment2 Interventions

SAR444245 is administered every 3 weeks on Day 1 of each cycle (21 days per cycle) and cetuximab is administered on Day 1, Day 8 and Day 15 of each cycle until progressive disease.

Group II: Cohort D1 (Sub-study 04): 3-6L CRC non-MSI-H any RASExperimental Treatment2 Interventions