SAR444200 + Atezolizumab for Cancer

Not currently recruiting at 28 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)

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment called SAR444200, alone or with atezolizumab, for certain advanced cancers. It aims to assess the treatment's safety and effectiveness in patients whose cancer has worsened despite other treatments. The trial seeks participants with specific cancers, such as liver cancer or certain lung cancers, who have not benefited from standard treatments. Eligible participants should have cancer that shows a specific marker called GPC3 and lack other effective treatment options. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive it.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that SAR444200, when used alone, has been safe at certain tested doses for patients with advanced solid tumors. Studies indicate that this treatment targets specific tumor cells, reducing unwanted side effects.

Specific safety details for the combination of SAR444200 with atezolizumab are not yet available. However, since SAR444200 alone has been well-tolerated, researchers hope for its safe use in combination treatments. It is important to note that this study is in its early stages, focusing mainly on safety. While promising evidence exists, the complete safety profile is still being developed. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about SAR444200 because it targets GPC3+ solid tumors, which isn't the focus of many existing therapies. Most current treatments for these cancers, like chemotherapy and radiation, target rapidly dividing cells but don't specifically hone in on GPC3, a protein often found in certain tumors. SAR444200, used alone or combined with atezolizumab, offers a new mechanism of action by potentially enhancing the immune system's response directly against these tumors. This targeted approach could mean more effective treatment with possibly fewer side effects.

What evidence suggests that this trial's treatments could be effective for cancer?

Research shows that SAR444200 targets a protein called Glypican-3 (GPC3), often present in certain cancer cells. By targeting this protein, SAR444200 enhances the immune system's ability to recognize and attack cancer cells. Early studies have shown that SAR444200 is safe and can help shrink tumors in patients with GPC3-positive solid tumors. In this trial, some participants will receive SAR444200 alone, while others will receive it in combination with atezolizumab. When combined with atezolizumab, SAR444200 remains safe and may still effectively fight these tumors. These findings suggest that SAR444200, both alone and with atezolizumab, may help treat cancers with GPC3. ^{1 3 4 6 7}

Who Is on the Research Team?

Clinical Sciences & Operations

Principal Investigator

Sanofi

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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]

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]

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 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 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 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]

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 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, 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]

Citations

1. onclive.com onclive.com/view/sar444200-demonstrates-safety-signals-of-clinical-activity-in-advanced-gpc3-hcc-other-solid-tumors

SAR444200 Demonstrates Safety, Signals of Clinical ... SAR444200-mediated targeting of GPC3-expressing solid tumors was safe and showed early signs of antitumor activity in a phase 1/2 study.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12375816/

Targeting Glypican-3 for Liver Cancer Therapy ... SAR444200 has received implied authorization for clinical trials, targeting GPC3-positive advanced solid tumors. SAR444200 is a GPC3/TCR ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT05450562

NCT05450562 | Dose Escalation and Expansion Study of ... This is Phase 1/Phase 2, open label, multiple cohort, first-in-human study to evaluate safety, PK, PDy and efficacy of SAR444200 as a monotherapy or in ...

4. researchgate.net researchgate.net/publication/374880064_1046P_Phase_III_open-label_study_on_an_anti-GPC3_T_cell_engager_SAR444200_in_patients_with_advanced_solid_tumors_Preliminary_dose_escalation_results

1046P Phase I/II open-label study on an anti-GPC3 T cell ... In a phase 1/2 open-label trial (EudraCT 2021-006623-17/NCT05450562), SAR444200 demonstrated a favorable safety profile in patients with ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11764197/

Mechanisms of Resistance and Novel Treatment Approaches In this review, we provide an overview of the current landscape of immunotherapy for unresectable HCC and delve into the tumor intrinsic and extrinsic ...

6. withpower.com withpower.com/trial/phase-2-neoplasms-6-2022-004ca

SAR444200 + Atezolizumab for Cancer · Info for Participants However, specific safety data for SAR444200 in combination with Atezolizumab is not detailed in the provided research. Show more.

7. congress.sanofimedical.com congress.sanofimedical.com/s3fs-public/2024-05/Pharmacokinetics%20and%20Biomarker%20Analysis%20From%20a%20Phase%2012%20Open-label%20Study%20of%20The%20Anti-GPC3%20T-cell%20Engager.pdf?VersionId=FnT4Qy_h2197ZLZCx73ivXDYzZbwDmCW

Maxime Chenard-Poirier1, Khaldoun Almhanna2, Darren Wan ... • Results suggest that SAR444200 was tolerated at the tested dose levels in patients with GPC3+ advanced solid tumors ... • Positive GPC3 expression on tumor ...