SAR444200 + Atezolizumab for Cancer

Recruiting at 25 trial locations

Overseen By Trial Transparency email recommended (Toll free number for US & Canada)

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Sanofi

Must not be taking: Immunosuppressants, Anti-PD1/PD-L1

Disqualifiers: Brain metastases, Cardiovascular disease, HIV, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 21

Duration: Variable (up to 2 years)

33 Participants Needed

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.

Do I need to stop my current medications to join the trial?

The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with the trial team or your doctor.

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. ^{1 2 3 4 5}

What data supports the effectiveness of the drug SAR444200 + Atezolizumab for cancer?

Atezolizumab, one of the drugs in the treatment, has shown effectiveness in enhancing the body's immune response against cancer in several studies, particularly in advanced lung cancer and other solid tumors. ^{1 2 3 4 5}

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. ^{1 5 6 7 8}

What safety data exists for SAR444200 + Atezolizumab in humans?

Atezolizumab, used in various cancers, has shown some mild skin reactions like rashes in about 20% of patients, but serious skin conditions like Stevens-Johnson syndrome are extremely rare. It has been studied in different cancers, including lung and liver cancer, and is generally considered safe, though it can have side effects when combined with chemotherapy. ^{1 5 6 7 8}

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. ^{1 2 4 9 10}

What makes the drug SAR444200 + Atezolizumab unique for cancer treatment?

The combination of SAR444200 and Atezolizumab is unique because it pairs a novel treatment (SAR444200) with Atezolizumab, an immune checkpoint inhibitor that enhances the body's immune response against cancer by blocking PD-L1, a protein that helps cancer cells evade the immune system. This combination aims to boost the immune system's ability to fight cancer more effectively than using Atezolizumab alone. ^{1 2 4 9 10}

Research Team

Clinical Sciences & Operations

Principal Investigator

Sanofi

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

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive SAR444200 as monotherapy or in combination with atezolizumab over a 21-day cycle until disease progression or unacceptable adverse events

Variable (up to 2 years)

Continuous treatment with regular 21-day cycles

End of Treatment

End of Treatment visit occurs 30 days ±7 days from last IMP administration or prior to initiation of further therapy

1 week

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Cemiplimab
• SAR444200

Trial Overview The 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

Group I: SAR444200 and Atezolizumab combination therapy - Dose Escalation Phase (Part 1B) Experimental Treatment 2 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 Treatment 1 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 Treatment 1 Intervention

SAR444200 will be administered as intravenous injection as monotherapy in participants with GPC3+ solid tumors over a 21-day cycle

Who Is Running the Clinical Trial?

Sanofi

Lead Sponsor

Trials

2,246

Recruited

4,085,000+

Paul Hudson

Sanofi

Chief Executive Officer since 2019

Degree in Economics from Manchester Metropolitan University

Christopher Corsico

Sanofi

Chief Medical Officer

MD from Cornell University, MPH in Chronic Disease Epidemiology from Yale University

Findings from Research

Atezolizumab, a monoclonal antibody targeting PD-L1, has shown significant improvements in progression-free and overall survival in patients with advanced non-small-cell lung cancer (NSCLC) and small-cell lung cancer (SCLC) when combined with chemotherapy, as demonstrated in the IMpower studies.

The safety profile of atezolizumab in combination with chemotherapy is acceptable, with common immune-related adverse events including rash (18-28%), hypothyroidism (8-15%), and hepatitis (5-17%), consistent with its known effects as a single agent, indicating no new safety concerns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The safety of atezolizumab plus chemotherapy for the treatment of metastatic lung cancer. Manzo, A., Carillio, G., Montanino, A., et al.[2022]

In a study involving 99 patients with previously treated advanced non-small cell lung cancer (NSCLC), the combination of daratumumab and atezolizumab did not show improved overall response rates compared to atezolizumab alone, with response rates of 4.3% versus 13.0%, respectively.

The study found no significant improvements in progression-free survival (PFS) or overall survival (OS) with the combination therapy, leading to the conclusion that daratumumab does not enhance the efficacy of atezolizumab in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Daratumumab Plus Atezolizumab in Previously Treated Advanced or Metastatic NSCLC: Brief Report on a Randomized, Open-Label, Phase 1b/2 Study (LUC2001 JNJ-54767414). Pillai, RN., Ramalingam, SS., Thayu, M., et al.[2022]

Atezolizumab, an immune checkpoint inhibitor, demonstrated significant efficacy in treating advanced solid tumors, particularly showing a non-progression rate of 44.4% in cervical cancer and 54.5% in follicular/papillary thyroid cancer among 474 patients enrolled in a phase II study.

The treatment was generally well-tolerated, with 55.3% of patients experiencing treatment-related adverse events, mostly mild to moderate, indicating a safety profile consistent with previous studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II multicohort study of atezolizumab monotherapy in multiple advanced solid cancers. Tabernero, J., Andre, F., Blay, JY., et al.[2022]

Atezolizumab significantly improved overall survival in patients with previously treated non-small-cell lung cancer compared to docetaxel, with median survival times of 13.8 months versus 9.6 months, respectively.

The safety profile of atezolizumab was favorable, with only 15% of patients experiencing grade 3 or 4 adverse events, compared to 43% in the docetaxel group, indicating it may be a safer treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab versus docetaxel in patients with previously treated non-small-cell lung cancer (OAK): a phase 3, open-label, multicentre randomised controlled trial. Rittmeyer, A., Barlesi, F., Waterkamp, D., et al.[2022]

Atezolizumab, an inhibitor of PD-L1, was found to be well tolerated in a phase 1-2 trial involving 90 children and young adults with refractory or relapsed solid tumors, with no fatal adverse events reported.

While only 5% of patients achieved an objective response, the study showed comparable serum concentrations of atezolizumab between children and young adults, suggesting potential for future research into optimizing immune checkpoint inhibitors for specific patient populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab for children and young adults with previously treated solid tumours, non-Hodgkin lymphoma, and Hodgkin lymphoma (iMATRIX): a multicentre phase 1-2 study. Geoerger, B., Zwaan, CM., Marshall, LV., et al.[2020]

Atezolizumab, an anti-PD-L1 therapy, demonstrated objective response rates of up to 40% in non-small cell lung cancer (NSCLC) and showed similar pharmacokinetics and safety profiles in Chinese patients compared to global studies.

In patients with PD-L1 positive tumors, the combination of atezolizumab with chemotherapy resulted in a significantly higher response rate of 46.2%, indicating enhanced efficacy when used alongside traditional treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Atezolizumab therapy in Chinese patients with locally advanced or metastatic solid tumors: An open-label, phase Ⅰ study]. Zhang, L., Gong, JF., Pan, HM., et al.[2022]

Atezolizumab, used for advanced non-small cell lung cancer and urothelial carcinoma, shows no significant differences in safety or efficacy across different dosing regimens, including 840 mg every 2 weeks and 1680 mg every 4 weeks compared to the approved 1200 mg every 3 weeks.

The study, which pooled data from multiple phase 1 and 3 trials involving various patient populations, suggests that the alternative dosing regimens can provide similar therapeutic benefits while offering more flexibility for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Alternative dosing regimens for atezolizumab: an example of model-informed drug development in the postmarketing setting. Morrissey, KM., Marchand, M., Patel, H., et al.[2020]

Atezolizumab, an anti-PD-L1 antibody used for treating advanced cancers like metastatic non-small cell lung cancer, has a low incidence of cutaneous side effects, with only 20% of patients experiencing mild rashes that did not require treatment.

There have been no reported cases of severe skin reactions such as Stevens-Johnson syndrome (SJS) or toxic epidermal necrolysis (TEN) associated with atezolizumab, suggesting a favorable safety profile for dermatological side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab-Induced Stevens-Johnson Syndrome in a Patient with Non-Small Cell Lung Carcinoma. Chirasuthat, P., Chayavichitsilp, P.[2020]

Atezolizumab shows consistent pharmacokinetics across various tumor types and treatment settings, whether used alone or in combination, supporting its flexible dosing regimens of 840 mg every 2 weeks, 1200 mg every 3 weeks, and 1680 mg every 4 weeks.

The efficacy of atezolizumab in combination therapies was found to be independent of drug exposure levels, and there was no significant increase in adverse events with higher doses, indicating a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Extension of the Alternative Intravenous Dosing Regimens of Atezolizumab into Combination Settings through Modeling and Simulation. Liu, SN., Marchand, M., Liu, X., et al.[2022]

Atezolizumab has been approved by the FDA as an adjuvant therapy for patients with stage II to IIIA non-small cell lung cancer (NSCLC) who have tumors expressing PD-L1 on 1% or more of tumor cells, based on the IMpower010 trial involving 1,005 patients.

The trial showed a significant improvement in disease-free survival (DFS) for patients receiving atezolizumab compared to those receiving best supportive care, with a hazard ratio of 0.66, indicating a 34% reduction in the risk of disease recurrence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Atezolizumab as Adjuvant Treatment following Surgical Resection and Platinum-Based Chemotherapy for Stage II to IIIA NSCLC. Mathieu, LN., Larkins, E., Sinha, AK., et al.[2023]

References

1. England pubmed.ncbi.nlm.nih.gov

The safety of atezolizumab plus chemotherapy for the treatment of metastatic lung cancer. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

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]

3. England pubmed.ncbi.nlm.nih.gov

Phase II multicohort study of atezolizumab monotherapy in multiple advanced solid cancers. [2022]

4. England pubmed.ncbi.nlm.nih.gov

Atezolizumab versus docetaxel in patients with previously treated non-small-cell lung cancer (OAK): a phase 3, open-label, multicentre randomised controlled trial. [2022]

5. England pubmed.ncbi.nlm.nih.gov

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]

6. China pubmed.ncbi.nlm.nih.gov

[Atezolizumab therapy in Chinese patients with locally advanced or metastatic solid tumors: An open-label, phase Ⅰ study]. [2022]

7. Germany pubmed.ncbi.nlm.nih.gov

Alternative dosing regimens for atezolizumab: an example of model-informed drug development in the postmarketing setting. [2020]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Atezolizumab-Induced Stevens-Johnson Syndrome in a Patient with Non-Small Cell Lung Carcinoma. [2020]

9. England pubmed.ncbi.nlm.nih.gov

Extension of the Alternative Intravenous Dosing Regimens of Atezolizumab into Combination Settings through Modeling and Simulation. [2022]

10. United States pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Atezolizumab as Adjuvant Treatment following Surgical Resection and Platinum-Based Chemotherapy for Stage II to IIIA NSCLC. [2023]