SAR444200 + Atezolizumab for Cancer
Recruiting in Palo Alto (17 mi)
+25 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 1 & 2
Waitlist Available
Sponsor: Sanofi
No Placebo Group
Breakthrough Therapy
Trial Summary
What is the purpose of this trial?
This trial is testing a new drug called SAR444200, either alone or with other cancer treatments. It targets adults with advanced cancer who have already received other treatments. The study will check if the drug is safe, how it behaves in the body, and if it helps treat cancer.
Do I need to stop my current medications to join the trial?
The trial protocol does not specify if you need to stop your current medications. However, certain conditions like significant cardiovascular disease, ongoing adverse effects from prior cancer therapy, or recent live-virus vaccination may affect eligibility. It's best to discuss your specific medications with the trial team.
What data supports the idea that SAR444200 + Atezolizumab for Cancer is an effective treatment?
The available research shows that Atezolizumab, when used alone, has been effective in treating various types of cancer, including non-small-cell lung cancer (NSCLC). It has been shown to improve survival rates and enhance the body's immune response against cancer cells. However, there is no specific data provided on the combination of SAR444200 with Atezolizumab for cancer treatment. Therefore, while Atezolizumab alone has demonstrated effectiveness, the effectiveness of the combination with SAR444200 is not directly supported by the provided information.12345
What safety data exists for SAR444200 and Atezolizumab in cancer treatment?
The safety data for Atezolizumab, a PD-L1 inhibitor, includes reports of mild maculopapular rash in 20% of patients, with no treatment required. There is a rare case of Atezolizumab-induced Stevens-Johnson Syndrome (SJS) reported. Studies have evaluated its safety in various cancers, including non-small cell lung cancer, esophageal cancer, gastric cancer, hepatocellular carcinoma, nasopharyngeal cancer, and urothelial carcinoma. Atezolizumab has been studied in combination with chemotherapy for metastatic lung cancer and in children and young adults with solid tumors and lymphomas. However, specific safety data for SAR444200 in combination with Atezolizumab is not detailed in the provided research.15678
Is the drug SAR444200 a promising treatment for cancer?
SAR444200, when combined with atezolizumab, could be promising because atezolizumab has shown to boost the body's immune response against cancer. It has been effective in improving survival rates in lung cancer patients and is approved for use in combination with other therapies. This suggests that SAR444200, when used with atezolizumab, might also help in fighting cancer effectively.124910
Eligibility Criteria
Adults with advanced solid tumors that have progressed after standard treatments or for whom no effective standard treatment exists. Specifically, it includes those with metastatic liver cancer (HCC) or non-liver solid tumors, and a subset with metastatic lung cancer (NSCLC). Participants must be able to consent and have measurable disease; however, they can't join if they have certain heart conditions, active infections like HIV or hepatitis B/C, severe autoimmune diseases, recent live vaccines, specific lung conditions, poor performance status, certain liver scores (for HCC), brain metastases, organ transplants history of severe immune-related side effects from previous cancer treatments.Inclusion Criteria
Cancer diagnosis for participants for Part 1A and Part 1B: Metastatic and/or unresectable HCC diagnosed by histology and/or cytology, or diagnosed clinically by the American Association for the Study of Liver Diseases (AASLD) criteria for participants with liver cirrhosis (participants without liver cirrhosis must be diagnosed histologically) OR Other histology/cytology proven advanced and/or metastatic non-HCC solid tumors not amenable to available standard of care: participants must have experienced disease progression on/after standard of care, or no acceptable standard curative or palliative treatments exist (or are no longer effective), according to Investigator judgement, or the participant declines standard of care therapy. Cancer diagnosis for participants for Part 2A: Metastatic NSCLC with no actionable driver gene mutants (such as epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK)), diagnosed by histology and/or cytology not amenable to available standard of care and must have progressed on/after therapy that included an anti-PD(L)-1 agent with or without platinum-based chemotherapy. Progressive disease should be observed during the course of anti-PD(L)-1 therapy or within 12 weeks from the last dose of anti-PD(L)-1 therapy Additional for Part 2A: At least 1 measurable lesion per RECIST 1.1 criteria For all participants: Positive GPC3 expression on tumor tissue as determined locally or centrally Capable of giving signed informed consent
Exclusion Criteria
Eastern Cooperative Oncology Group (ECOG) performance status of ≥2 Predicted life expectancy ≤3 months For participants with HCC: Child Pugh Class B or C liver score within 14 days of initiation of IMP Participants with Child Pugh Class B-7 score are allowed for Part 1A Known active brain metastases or leptomeningeal metastases History of allogenic or solid organ transplant Treatment-related immune-mediated (or immune-related) AEs from immune-modulatory agents (including but not limited to anti-PD1/PD-L1 agents and anti-cytotoxic T lymphocyte associated protein 4 monoclonal antibodies) that caused permanent discontinuation of the agent, or that were Grade 4 in severity Significant cardiovascular disease within 3 months prior to initiation of IMP, uncontrolled arrhythmia requiring medication, or unstable angina Ongoing AEs caused by any prior anti-cancer therapy >Grade 2 Known uncontrolled human immunodeficiency virus (HIV), hepatitis B infection, or known untreated current hepatitis C infection Known second malignancy either progressing or requiring active treatment within the last year For combination therapy: Ongoing or recent (within 5 years) evidence of significant autoimmune disease that required treatment with systemic immunosuppressive treatments, which may suggest risk for immune-related adverse events Receipt of a live-virus vaccination within 28 days of planned treatment start For Part 2A, has received prior GPC3 targeted anticancer treatment Current pneumonitis or interstitial lung disease, or history of interstitial lung disease or pneumonitis that required oral or IV glucocorticoids to assist with management
Treatment Details
Interventions
- Cemiplimab (Monoclonal Antibodies)
- SAR444200 (Monoclonal Antibodies)
Trial OverviewThe trial is testing SAR444200 alone or combined with Atezolizumab in adults with advanced cancers. It's an early-stage study to check the safety of different doses (Phase 1) and see how well the drugs work together (Phase 2). The goal is also to understand how the body processes these drugs and their impact on tumor growth.
Participant Groups
3Treatment groups
Experimental Treatment
Group I: SAR444200 and Atezolizumab combination therapy - Dose Escalation Phase (Part 1B)Experimental Treatment2 Interventions
SAR444200 in combination with atezolizumab will be administered as intravenous injection in participants with GPC3+ solid tumors over a 21-day cycle
Group II: SAR444200 - Dose Expansion Phase (Part 2A)Experimental Treatment1 Intervention
SAR444200 will be administered as intravenous injection in participants with GPC3+ NSCLC over a 21-day cycle
Group III: SAR444200 - Dose Escalation Phase (Part 1A)Experimental Treatment1 Intervention
SAR444200 will be administered as intravenous injection as monotherapy in participants with GPC3+ solid tumors over a 21-day cycle
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Investigational Site Number : 1240002Toronto, Canada
USC Norris Comprehensive Cancer Center- Site Number : 8400004Los Angeles, CA
Icahn School of Medicine at Mount Sinai- Site Number : 8400005New York, NY
Lifespan Corporation- Site Number : 8400002Providence, RI
More Trial Locations
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Who Is Running the Clinical Trial?
SanofiLead Sponsor
References
The safety of atezolizumab plus chemotherapy for the treatment of metastatic lung cancer. [2022]Atezolizumab is a humanized monoclonal antibody against PD-L1 capable of enhancing antitumor immune activity, with a demonstrated activity as single agent in patients with advanced non-small-cell lung cancer (NSCLC).
Daratumumab Plus Atezolizumab in Previously Treated Advanced or Metastatic NSCLC: Brief Report on a Randomized, Open-Label, Phase 1b/2 Study (LUC2001 JNJ-54767414). [2022]The programmed death-ligand 1 inhibitor atezolizumab improves progression-free survival (PFS) and overall survival (OS) for patients with previously treated advanced NSCLC. Preclinical studies indicate that targeting CD38-positive cells with daratumumab may synergistically enhance atezolizumab's antitumor activity by increasing the effector T-cell activity.
Phase II multicohort study of atezolizumab monotherapy in multiple advanced solid cancers. [2022]The programmed death-ligand 1 inhibitor atezolizumab had shown clinical activity against several advanced malignancies.
Atezolizumab versus docetaxel in patients with previously treated non-small-cell lung cancer (OAK): a phase 3, open-label, multicentre randomised controlled trial. [2022]Atezolizumab is a humanised antiprogrammed death-ligand 1 (PD-L1) monoclonal antibody that inhibits PD-L1 and programmed death-1 (PD-1) and PD-L1 and B7-1 interactions, reinvigorating anticancer immunity. We assessed its efficacy and safety versus docetaxel in previously treated patients with non-small-cell lung cancer.
Atezolizumab for children and young adults with previously treated solid tumours, non-Hodgkin lymphoma, and Hodgkin lymphoma (iMATRIX): a multicentre phase 1-2 study. [2020]Atezolizumab is an inhibitor of PD-L1, which can lead to enhanced anticancer T-cell activity. We aimed to evaluate the safety, pharmacokinetics, and activity of atezolizumab in children and young adults with refractory or relapsed solid tumours, with known or expected PD-L1 expression.
[Atezolizumab therapy in Chinese patients with locally advanced or metastatic solid tumors: An open-label, phase Ⅰ study]. [2022]To evaluate pharmacokinetics (PK), efficacy, and safety of atezolizumab (anti-PD-L1) in high interest cancers in China, including esophageal cancer (EC), gastric cancer (GC), hepatocellular carcinoma (HCC), nasopharyngeal cancer (NPC), and non-small cell lung can-cer (NSCLC).
Alternative dosing regimens for atezolizumab: an example of model-informed drug development in the postmarketing setting. [2020]To determine the exposure-response (ER) relationships between atezolizumab exposure and efficacy or safety in patients with advanced non-small cell lung cancer (NSCLC) or urothelial carcinoma (UC) and to identify alternative dosing regimens.
Atezolizumab-Induced Stevens-Johnson Syndrome in a Patient with Non-Small Cell Lung Carcinoma. [2020]Atezolizumab is a humanized anti-PD-L1 immune checkpoint antibody that is currently used in many kinds of advanced carcinoma including metastatic non-small cell lung cancer. The cutaneous side effect profile reported only 20$ of the patients which had only mild maculopapular rash that required no treatment. There is no case report of anti-PD-L1 antibody-induced Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) eruptions. To the best of our knowledge, there is no case report of atezolizumab-induced SJS or SJS/TEN induced by anti-PD-L1 immune checkpoint antibodies. We believe that our report will be useful to dermatologists who are consultants in the inpatient settings, as atezolizumab is an anti-neoplastic agent that has a potential to be used in multiple malignancies.
Extension of the Alternative Intravenous Dosing Regimens of Atezolizumab into Combination Settings through Modeling and Simulation. [2022]Atezolizumab is approved as an intravenous (IV) infusion for use as a single agent and in combination with other therapies in a number of indications. The objectives of this publication are to characterize atezolizumab pharmacokinetics (PK) across indications with the available clinical data from one phase I and eight phase III studies, to determine the exposure-response (ER) relationships in combination settings across a variety of tumor types, and to provide the clinical safety to support the extension of the 840 mg q2w, 1200 mg q3w, and 1680 mg q4w IV dosing regimens across various indications in combination settings. Across all clinical studies, atezolizumab PK remained in the dose-linear range and were similar across tumor types when used in combination therapy or as a monotherapy. In the combination studies, efficacy was independent of the exposures tested and there was no significant increase in adverse events with increasing atezolizumab exposure (flat ER). The safety profile of atezolizumab in the individual combination studies was generally consistent with the established safety profile of atezolizumab, the combination partners, and the disease under study. The similar atezolizumab PK across monotherapy and combination therapy settings as well as the flat ER in new tumor types and combination therapies support the use of the 3 interchangeable atezolizumab dosing regimens in the combination setting. Atezolizumab is now approved with 3 interchangeable IV dosing regimens of 840 mg q2w, 1200 mg q3w, and 1680 mg q4w for single-agent and combination therapy use in the USA and EU.
FDA Approval Summary: Atezolizumab as Adjuvant Treatment following Surgical Resection and Platinum-Based Chemotherapy for Stage II to IIIA NSCLC. [2023]On October 15, 2021, the FDA approved atezolizumab as adjuvant therapy in patients with stage II to IIIA non-small cell lung cancer (NSCLC) whose tumors have programmed cell death ligand 1 (PD-L1) expression on ≥1% of tumor cells (TC), as detected by an FDA-approved test. The approval was based on results from the IMpower010 trial, in which 1,005 patients with NSCLC who had completed tumor resection and cisplatin-based adjuvant chemotherapy were randomly assigned 1:1 to receive atezolizumab for 16 cycles or best supportive care. The primary endpoint of disease-free survival (DFS) as assessed by investigator was tested hierarchically in the following analysis populations: stage II-IIIA NSCLC with PD-L1 expression on ≥1% of TCs (PD-L1 ≥ 1% TC); all randomly assigned patients with stage II-IIIA NSCLC; and the intent-to-treat population comprising all randomly assigned patients. At the prespecified interim DFS analysis, IMpower010 demonstrated a statistically significant and clinically meaningful improvement in DFS in the stage II-IIIA PD-L1 ≥ 1% TC analysis population, with an HR of 0.66 (95% confidence interval, 0.50-0.88; P = 0.004) favoring the atezolizumab arm. The safety profile of atezolizumab was generally consistent with known toxicities of anti-PD-(L) antibodies. The VENTANA PD-L1 (SP263) Assay (Ventana Medical Systems, Inc.) was contemporaneously approved as a companion diagnostic device to select patients with NSCLC who are PD-L1 ≥ 1% TC for adjuvant treatment with atezolizumab. Atezolizumab is the first immune checkpoint inhibitor approved by FDA for the adjuvant treatment of NSCLC.