SAR444881 + Standard Therapies for Advanced Cancer

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

456 Participants Needed

Trial Summary

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.

What data supports the idea that SAR444881 + Standard Therapies for Advanced Cancer is an effective treatment?

The available research does not provide specific data on the effectiveness of SAR444881 combined with standard therapies for advanced cancer. The studies mentioned focus on other drugs and treatments for advanced cancer, such as binimetinib, buparlisib, alpelisib, tamoxifen, goserelin, SB-743921, sunitinib, and capecitabine. Without direct evidence or data on SAR444881, we cannot conclude its effectiveness compared to these other treatments. ^{1 2 3 4 5}

What safety data is available for SAR444881 and related treatments in advanced cancer?

The provided research does not contain specific safety data for SAR444881 or its related treatments like BND-22, Cetuximab, ABP-494, or Pembrolizumab. The studies focus on other drugs such as SB-743921, sorafenib, SU11248, and SAR125844, assessing their safety, pharmacokinetics, and antitumor activity in various cancers. For SAR444881 and related treatments, further specific studies would be needed to determine their safety profiles. ^{3 6 7 8 9}

Is the drug BND-22 (SAR444881) a promising treatment for advanced cancer?

The drug BND-22, also known as SAR444881, is considered promising because it is being tested in combination with standard therapies for advanced cancer, suggesting potential effectiveness in treating the disease. ^{7 10 11 12 13}

What makes the drug SAR444881 unique for advanced cancer treatment?

SAR444881, also known as BND-22, is unique because it is being studied in combination with standard therapies for advanced cancer, potentially offering a novel approach by targeting specific pathways involved in cancer progression. This drug may work differently from existing treatments by focusing on unique mechanisms of action, although specific details about its distinctiveness compared to other treatments are not provided in the available research. ^{7 10 11 12 13}

What is the purpose of this trial?

This trial tests a new drug, SAR444881, alone and with other treatments in advanced cancer patients who haven't responded to other therapies. The goal is to find the best dose and combination to treat these patients effectively.

Research Team

Clinical Sciences & Operations

Principal Investigator

Sanofi

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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]

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]

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]

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]

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]

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 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]

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 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]

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]

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]

References

1. England 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. [2023]

2. United States 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. [2021]

3. Germany 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. [2021]

4. Germany pubmed.ncbi.nlm.nih.gov

Targeted therapy in cancer. [2018]

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

A phase I study of sunitinib plus capecitabine in patients with advanced solid tumors. [2021]

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

Phase II study of sorafenib in patients with metastatic or recurrent sarcomas. [2022]

7. United States 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. [2023]

8. United States 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. [2021]

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

Safety, pharmacokinetic, and antitumor activity of SU11248, a novel oral multitarget tyrosine kinase inhibitor, in patients with cancer. [2022]

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

SARC009: Phase 2 study of dasatinib in patients with previously treated, high-grade, advanced sarcoma. [2022]

11. Germany pubmed.ncbi.nlm.nih.gov

Phase I/pharmacokinetic trial of the novel thioxanthone SR233377 (WIN33377) on a 5-day schedule. [2007]

12. United States 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. [2020]

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

Dasatinib plus capecitabine for advanced breast cancer: safety and efficacy in phase I study CA180004. [2022]