SAR444881 + Standard Therapies for Advanced Cancer

No longer recruiting at 43 trial locations

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

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Biond Biologics

Must not be taking: Corticosteroids, Immunosuppressives

Disqualifiers: Autoimmune disease, Brain metastases, HIV, others

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

Compensation: Varies

Number of Visits: 4

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new cancer treatment called SAR444881 (also known as BND-22) for patients with advanced cancer that cannot be surgically removed or has spread. It examines the effectiveness of this treatment alone or in combination with other standard cancer drugs. Potential participants include those with specific types of cancer, such as lung, stomach, or colorectal cancer, who have not responded to typical treatments. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify if you must stop taking your current medications. However, you cannot have taken cytotoxic or non-cytotoxic anti-cancer agents within 4 weeks before the trial, and you must not use other investigational drugs or have had a live attenuated vaccine within 28 days before the trial.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain cancer treatments at least 4 weeks before starting the study. If you're on other investigational drugs or have had a live vaccine recently, you may also need to wait 28 days.

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

Researchers are studying the safety of SAR444881, both alone and in combination with treatments like pembrolizumab and cetuximab. Although specific safety information for SAR444881 is not yet available, pembrolizumab and cetuximab are well-known drugs. The FDA has approved pembrolizumab for treating various cancers, indicating it is generally considered safe, though it can have side effects.

SAR444881 is a new drug in the early stages of testing, and researchers are determining its safety. They are focused on finding a safe dose and identifying any side effects. So far, there are no specific reports on how well people tolerate SAR444881. However, since it is being tested with other approved treatments, researchers are closely monitoring for any negative effects.

In summary, while pembrolizumab and cetuximab have established safety records, SAR444881 is still under careful study to understand its safety profile. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about SAR444881 because it represents a new frontier in targeting advanced cancers like non-small cell lung cancer, gastric cancer, and colorectal carcinoma. Unlike most treatments that focus on a single pathway, SAR444881 is being studied in combination with other drugs like pembrolizumab and cetuximab, potentially enhancing the immune response against tumors. Its unique dose optimization and expansion phases aim to fine-tune its effectiveness and safety, paving the way for more personalized cancer care. This multi-targeted approach could offer hope for patients who have limited options with existing therapies.

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

Research has shown that SAR444881, also known as BND-22, targets ILT2, a part of the immune system that can slow the body's fight against tumors. Early studies have demonstrated promising results, with SAR444881 effectively fighting tumors in lab tests. This trial will test SAR444881 in various treatment arms. One arm will combine SAR444881 with pembrolizumab, an approved cancer treatment, to potentially enhance the immune system's ability to fight cancer. Another arm will combine SAR444881 with cetuximab, another cancer treatment, to explore its effectiveness. These combinations aim to treat cancers such as non-small cell lung cancer, gastric cancer, and colorectal cancer by boosting the immune response and attacking cancer cells. ^{1 4 6 7 8}

Who Is on the Research Team?

Clinical Sciences & Operations

Principal Investigator

Sanofi

Are You a Good Fit for This Trial?

This trial is for adults with advanced solid tumors that can't be removed by surgery or have spread, and who haven't responded to standard treatments. They must be physically able to perform daily activities (ECOG 0-1) and have proper organ function. Specific cancers like lung, breast, head and neck among others are included depending on the study part.

Inclusion Criteria

Histologic confirmation of malignancy

Measurable disease per RECIST v1.1

My cancer is one of the following: head and neck, stomach, or non-small cell lung cancer.

Exclusion Criteria

I am on steroids or other drugs that suppress my immune system.

I have had a solid organ or bone marrow transplant.

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

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

SAR444881 administered alone and in combination with pembrolizumab and cetuximab to determine the recommended dose

34 months

Every 2-3 weeks (in-person)

Dose Optimization/Expansion

SAR444881 administered in combination with other therapeutics to optimize and expand dosing

28 months

Every 2-3 weeks (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

24 months

What Are the Treatments Tested in This Trial?

Interventions

• BND-22
• Cetuximab
• Pembrolizumab

Trial Overview

The trial tests SAR444881 alone and in combinations with pembrolizumab, cetuximab, carboplatin, or pemetrexed. It has two parts: dose escalation to find safe levels of SAR444881 (alone/with drugs), then dose optimization/expansion where effective doses are given more widely. Part of the second phase involves random selection for treatment groups.

How Is the Trial Designed?

Group I: SAR444881 in Combination with Pembrolizumab Dose Escalation (Sub-Part 1B) Experimental Treatment 2 Interventions

Standard "3 + 3" dose escalation design with enrollment of at least 3 participants per dose level cohort. SAR444881 and pembrolizumab will be administered intravenously (IV), every 3 weeks (Q3W).

Group II: SAR444881 in Combination with Cetuximab Dose Escalation (Sub-Part 1C) Experimental Treatment 2 Interventions

Standard "3 + 3" dose escalation design with enrollment of at least 3 participants per dose level cohort. SAR444881 and cetuximab will be administered intravenously (IV), every 2 weeks (Q2W).

Group III: SAR444881 Dose Optimization (Sub-Part 2A) Experimental Treatment 5 Interventions

SAR444881 Dose Optimization in combination with pembrolizumab/carboplatin/pemetrexed, pembrolizumab, or cetuximab. The indication for the combination cohorts will be non-squamous non-small cell lung cancer (NSCLC), gastric cancer or gastro-esophageal junction adenocarcinoma (GC/GEJ), colorectal carcinoma (CRC) any RAS. Enrollment will start after the recommended dose(s) of SAR444881 have been determined based on data from Sub-Parts 1A, 1B, and 1C.

Group IV: SAR444881 Dose Expansion (Sub-Part 2B) Experimental Treatment 1 Intervention

The indication for this monotherapy cohort is cholangiocarcinoma. Enrollment will be opened based on emerging data from the dose-escalation phase and combination optimization data.

Group V: SAR444881 Dose Escalation (Sub-Part 1A) Experimental Treatment 1 Intervention

Standard "3 + 3" dose escalation design with enrollment of at least 3 participants per dose level cohort. SAR444881 will be administered intravenously (IV), every 2 weeks (Q2W).

Who Is Running the Clinical Trial?

Biond Biologics

Lead Sponsor

Trials

2

Recruited

740+

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

In a phase 2 trial involving 200 patients with advanced sarcoma, dasatinib showed limited efficacy, with only 6 out of 47 patients with leiomyosarcoma and 8 out of 42 with undifferentiated pleomorphic sarcoma demonstrating clinical benefit, indicating a low clinical benefit rate.

The study found that dasatinib was inactive as a single agent for most sarcoma subtypes, leading to early termination of enrollment in 5 cohorts due to insufficient activity, while the median overall survival for participants was 8.6 months.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

SARC009: Phase 2 study of dasatinib in patients with previously treated, high-grade, advanced sarcoma. Schuetze, SM., Wathen, JK., Lucas, DR., et al.[2022]

In a phase I trial involving 25 patients with solid tumors, SR233377 was found to have tolerable side effects, including mild neutropenia and nausea, but was limited by dose-dependent QTc prolongation, which can increase the risk of serious heart issues.

Despite the safety concerns, some patients experienced significant tumor growth inhibition lasting over 4 months, indicating potential efficacy of SR233377 against solid tumors, although further studies with different dosing schedules are needed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I/pharmacokinetic trial of the novel thioxanthone SR233377 (WIN33377) on a 5-day schedule. Stevenson, JP., DeMaria, D., Reilly, D., et al.[2007]

SAR125844, a selective c-Met kinase inhibitor, was found to have acceptable tolerability in a phase I trial with 38 Asian patients, including those with gastric cancer and MET amplification, with the maximum tolerated dose established at 570 mg/m2.

While no objective responses were observed in the initial dose-escalation cohort, modest antitumor activity was noted in the dose-expansion cohort, particularly in patients with MET-amplified gastric cancer, where two patients achieved partial responses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I dose-escalation study of the c-Met tyrosine kinase inhibitor SAR125844 in Asian patients with advanced solid tumors, including patients with MET-amplified gastric cancer. Shitara, K., Kim, TM., Yokota, T., et al.[2023]

The combination of the MET inhibitor crizotinib and the c-SRC inhibitor dasatinib was found to be safe for administration in a phase I study involving 61 patients, but it had a high rate of dose-limiting toxicities (DLTs), particularly at higher doses.

While some patients experienced partial responses and stable disease for at least 6 months, the overall efficacy was limited, suggesting that the tolerability issues may hinder the use of this combination in precision therapy for cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I study of the combination of crizotinib (as a MET inhibitor) and dasatinib (as a c-SRC inhibitor) in patients with advanced cancer. Kato, S., Jardim, DL., Johnson, FM., et al.[2020]

In a multicenter phase II study involving 145 patients with recurrent or metastatic sarcoma, sorafenib showed a partial response rate of 14% specifically in patients with angiosarcoma, indicating some efficacy for this subtype.

Despite its limited effectiveness in other sarcoma types, sorafenib was associated with significant adverse events, leading to dose reductions in 61% of patients, highlighting the need for careful monitoring and potential combination therapies to enhance its therapeutic impact.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II study of sorafenib in patients with metastatic or recurrent sarcomas. Maki, RG., D'Adamo, DR., Keohan, ML., et al.[2022]

The combination of dasatinib (100 mg daily) and capecitabine (1,000 mg/m² twice daily) was found to be tolerable and resulted in clinical benefits for 56% of patients with advanced breast cancer, with a median progression-free survival of 14.4 weeks.

The study identified the maximum tolerated dose (MTD) and observed significant changes in biomarkers related to angiogenesis, indicating that this treatment may have antiangiogenic effects, as evidenced by decreases in plasma VEGF-A and increases in VEGFR-2 and collagen-IV.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dasatinib plus capecitabine for advanced breast cancer: safety and efficacy in phase I study CA180004. Somlo, G., Atzori, F., Strauss, LC., et al.[2022]

The combination of sorafenib and ifosfamide was found to be safe at a recommended dose of sorafenib 400 mg twice daily and ifosfamide 6 g/m², with some dose-limiting toxicities observed, including severe fatigue and encephalopathy.

Out of 12 patients with advanced sarcoma, 8 achieved stable disease for over 12 weeks, indicating limited preliminary antitumor activity, which supports further investigation in a phase II study.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I trial of sorafenib in combination with ifosfamide in patients with advanced sarcoma: a Spanish group for research on sarcomas (GEIS) study. Martín-Liberal, J., López-Pousa, A., Broto, JM., et al.[2021]

The maximum-tolerated dose (MTD) of SB-743921 was established at 4 mg/m², with neutropenia being the most common dose-limiting toxicity observed in a study involving 44 patients with advanced solid tumors or relapsed/refractory lymphoma.

One patient experienced a durable objective response lasting 11 months, and 6 patients had stable disease for over four treatment cycles, indicating promising efficacy and a favorable safety profile for further development of SB-743921.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A first in human study of SB-743921, a kinesin spindle protein inhibitor, to determine pharmacokinetics, biologic effects and establish a recommended phase II dose. Holen, KD., Belani, CP., Wilding, G., et al.[2021]

Sunitinib, an oral multitargeting tyrosine kinase inhibitor, was found to have manageable toxicity at a recommended dose of 50 mg/day, with common side effects including sore mouth, edema, and thrombocytopenia.

The drug demonstrated antitumor activity in various cancers, including renal cell carcinoma, with six objective responses observed, indicating its potential for further studies in treating advanced malignancies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety, pharmacokinetic, and antitumor activity of SU11248, a novel oral multitarget tyrosine kinase inhibitor, in patients with cancer. Faivre, S., Delbaldo, C., Vera, K., et al.[2022]

In a phase Ib study involving 89 patients with advanced solid tumors, the combination of binimetinib (a MEK inhibitor) and buparlisib (a PI3K inhibitor) showed some efficacy, particularly in RAS/BRAF-mutant ovarian cancer, where 12% of patients achieved a partial response.

However, the treatment was associated with significant toxicities, leading to a lower than expected dose intensity, suggesting that alternative dosing strategies, like pulsatile dosing, may be necessary to improve safety and tolerability in future trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase Ib Study of Combination Therapy with MEK Inhibitor Binimetinib and Phosphatidylinositol 3-Kinase Inhibitor Buparlisib in Patients with Advanced Solid Tumors with RAS/RAF Alterations. Bardia, A., Gounder, M., Rodon, J., et al.[2023]

Targeted therapies in cancer treatment have made significant progress due to advancements in genomics and tumor molecular profiling, which help understand cancer mechanisms and treatment resistance.

Despite these advancements, there remains a gap between preclinical findings and effective therapies, largely due to challenges in drug development, high costs, and limited patient access to clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeted therapy in cancer. Tsimberidou, AM.[2018]

The study established the recommended phase 2 doses (RP2D) for alpelisib (350 mg) and buparlisib (100 mg) when combined with tamoxifen and goserelin in premenopausal women with hormone receptor-positive, HER2-negative advanced breast cancer, showing that both combinations were well-tolerated.

Patients treated with alpelisib experienced a longer progression-free survival of 25.2 months compared to 20.6 months for those on buparlisib, suggesting that alpelisib may be a more effective option for this patient group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Phase Ib Study of Alpelisib or Buparlisib Combined with Tamoxifen Plus Goserelin in Premenopausal Women with HR-Positive HER2-Negative Advanced Breast Cancer. Lu, YS., Lee, KS., Chao, TY., et al.[2021]

In a phase I study involving 73 patients with advanced solid tumors, the combination of sunitinib and capecitabine was found to have an acceptable safety profile, with the maximum-tolerated dose established for different treatment schedules.

The treatment led to nine confirmed partial responses in various cancers, indicating potential antitumor activity, particularly in pancreatic cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase I study of sunitinib plus capecitabine in patients with advanced solid tumors. Sweeney, CJ., Chiorean, EG., Verschraegen, CF., et al.[2021]

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SAR444881 + Standard Therapies for Advanced Cancer

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990O Final results from phase I, first-in-human, dose ...

SAR444881 (SAR), a first-in-class humanized IgG4 mAb, selectively binds to ILT2 on NK/T cells/macrophages, blocking its interaction with MHC I. Here, we report ...