A first-in-human, dose escalation and dose expansion study of SAR445877 in adult participants with advanced solid tumors

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Sanofi-Aventis Recherche & Developpement

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

29 Jan 2025 → ongoing

Decision date (initial)

2024-10-31

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Sanofi-Aventis Recherche & Developpement

External identifiers

EU CT number

2023-507141-28-00

EudraCT number

2022-001239-95

WHO UTN

U1111-1277-4827

ClinicalTrials.gov

NCT05584670

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Others, Pharmacodynamic, Safety, Pharmacokinetic, Efficacy

Dose escalation: To determine the maximum tolerated dose (MTD) or maximum administered dose (MAD), recommended dose(s), and the overall safety and tolerability profile of SAR445877 when administered as monotherapy or in combination
Japan Cohort F: To confirm the tolerability of SAR445877 monotherapy in Japanese participants

Dose expansion/optimization: To determine the objective response rate (ORR) of SAR445877 administered as monotherapy or in combination at the recommended dose(s)

Secondary objectives 5

1. Dose escalation and Japan Cohort F: to assess preliminary clinical activity of SAR445877 monotherapy or in combination at the recommended dose(s)
2. Dose escalation, expansion/optimization: To characterize the pharmacokinetic (PK) profile of SAR445877 when administered as monotherapy or in combination and the PK of combined therapies Japan Cohort F: To characterize the pharmacokinetic (PK) profile of SAR445877 when administered as monotherapy
3. Dose escalation, expansion/optimization and Japan Cohort F: To assess the potential immunogenicity of SAR445877 and ADG126
4. Dose expansion/optimization: To assess other indicators of antitumor activity
5. Dose expansion/optimization: To characterize the safety profile of SAR445877 monotherapy or in combination

Conditions and MedDRA coding

Solid tumor

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 23

1. Dose escalation Part 1A and Japan Cohort F Participants with advanced unresectable or metastatic solid tumors for which, in the judgement of the investigator, no standard alternative therapy is available or is not in the best interest of the participant
2. Dose expansion/optimization Part 2 Cancer diagnosis:For participants in Cohorts C1 and C2 (Part 2A): Participants with unknown HER2/neu status must have their HER2/neu status determined locally. Participants with HER2/neu negative are eligible. Participants with HER2/neu positive tumors must have documentation of disease progression on treatment containing an approved HER2 targeted therapy to be eligible.
3. Measurable Disease: At least 1 measurable lesion per RECIST 1.1 criteria.
4. NOTE: Other Inclusion criteria may apply. The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.
5. Dose expansion/optimization Part 2 Cancer diagnosis: Participants in Part 2A Cohorts E1 and E2, Part 2B Cohort E3 and Part 2D Cohorts H1 and H2: Histologically or cytologically confirmed diagnosis of advanced unresectable or metastatic colorectal cancer.
6. Dose expansion/optimization Part 2 Cancer diagnosis: Participants in Part 2A Cohorts E1, and E2 and Part 2B Cohort E3 MSI status: Participants must have MSI status known or determined locally and must have non- MSI-H disease to be eligible.
7. Dose expansion/optimization Part 2 Cancer diagnosis:For participants in Cohorts C1 and C2 (Part 2A): Disease with any CPS scoring. No need for CPS determination at local laboratory.
8. Dose expansion/optimization Part 2 Cancer diagnosis: Participants in Part 2A Cohorts E1, E2, Part 2B Cohort E3 and Part 2D Cohorts H1 and H2: Participants with RAS-mutant and BRAF-mutant colorectal cancer are eligible for enrollment.
9. Dose expansion/optimization Part 2 Cancer diagnosis: Part 2C Cohorts G1, G2 and G3: Participants with histologically confirmed unresectable locally advanced or metastatic melanoma
10. Prior anticancer therapy (For dose expansion/optimization Part 2 only): Participants in Cohorts A1 and A2: Participants must have received at least 1 systemic therapy for the metastatic setting and must not be amenable to the available SOC.
11. Prior anticancer therapy (For dose expansion/optimization Part 2 only): Participants in Cohort B: Participants who have received at least 1 prior anticancer therapy, including an anti-PD1/PD-L1 containing regimen, and for whom have progressed after a primary or secondary resistance to an anti-PD1/PD-L1.
12. Capable of giving signed informed consent.
13. Prior anticancer therapy (For dose expansion/optimization Part 2 only): Participants in Cohorts C1 and C2: Participants should have failed or relapsed after at least 1 prior line of treatment which may or may not include an anti-PD1/PD-L1-based treatment depending on local standard of care.
14. Prior anticancer therapy (For dose expansion/optimization Part 2 only): Participants in Cohort D: Participants must have received at least 1 systemic therapy for their advanced/ metastatic setting and must not be amenable to the available SOC.
15. Prior anticancer therapy (For dose expansion/optimization Part 2 only): Participants in Part 2A Cohorts E1 and E2 and Part 2D Cohorts H1 and H2 should have failed or relapsed on at least 2 prior regimens.
16. Prior anticancer therapy (For dose expansion/optimization Part 2 only): Participants in cohort E3 should have failed or relapsed on at least 1 prior regimen. Participants who have received cetuximab or other anti-EGFR therapy as part of their prior line of treatment are eligible.
17. Prior anticancer therapy (For dose expansion/optimization Part 2 only): Part 2C Cohorts G1, G2 and G3: Participants must have received at least one prior line of therapy for advanced/metastatic melanoma and/or does not have any standard of care (SoC) treatment option or decline or is intolerant to be treated with SoC treatment.
18. Part 2D: Adequate coagulation function for all participants. For participants receiving anti-coagulant therapy (except platelet anti-aggregates) the adequate therapeutic levels of INR should be confirmed.
19. Dose expansion/optimization Part 2 Cancer diagnosis: Participants in Cohorts A1 and A2: (Part 2A): Histologically or cytologically confirmed diagnosis of metastatic non-small cell lung cancer (NSCLC)
20. Dose expansion/optimization Part 2 Cancer diagnosis: Participants in Cohort B: (Part 2A): Histologically or cytologically confirmed diagnosis of advanced unresectable or metastatic hepatocellular carcinoma (HCC), or clinically by American Association for the Study of Liver Diseases (AASLD) criteria in cirrhotic participants (participants without cirrhosis must have had histological confirmation of diagnosis).
21. Dose expansion/optimization Part 2 Cancer diagnosis:Participants in Cohorts C1 and C2 (Part 2A): Histologically or cytologically confirmed diagnosis of advanced unresectable or metastatic gastric cancer (GC) or Siewert Type 2 & 3 gastro esophageal junction (GEJ) adenocarcinoma.
22. Dose escalation Part 1B: Participants with advanced unresectable or metastatic melanoma, NSCLC; renal cell carcinoma (RCC); HCC, colorectal cancer (MSI-H/dMMR), malignant pleural mesothelioma or esophageal squamous cell carcinoma (ESCC). and for who, in the judgement of the investigator, no standard alternative therapy is available or is not in the best interest of the participant.
23. Dose expansion/optimization Part 2 Cancer diagnosis:For participants in Cohorts C1 and C2 (Part 2A): Participants must have MSI or MMR status known or determined locally and must have non-MSI-H or proficient MMR (pMMR) disease to be eligible.

Exclusion criteria 13

1. Eastern Cooperative Oncology Group (ECOG) performance status of ≥2.
2. Predicted life expectancy ≤3 months.
3. For participants with HCC- Cohort B (Part 2): Child Pugh Class B or C liver score. Participants with Child Pugh Class B-7 score are allowed for Part 1.
4. Diagnosed of any other malignancies, either progressing or requiring active treatments, within 2 years prior to enrollment.
5. Known active brain metastases or leptomeningeal metastases.
6. History of 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 or have not resolved to Grade ≤1.
7. Has any condition requiring ongoing/continuous corticosteroid therapy (>10 mg prednisone/day or an anti-inflammatory equivalent) within 1 week prior to the first dose of the study medicine.
8. Any clinically significant cardiac (including valvular) or vascular (thromboembolic disorders) disease, within 6 months prior to the first IMP administration.
9. Ongoing or recent (within 2 years) evidence of significant autoimmune disease that required treatment with systemic immunosuppressive treatments, which may suggest risk for immune-related adverse events.
10. Has a known history or any evidence of interstitial lung disease or active, non-infectious pneumonitis within 3 years prior to the first dose of the study drug.
11. Organ transplant requiring immunosuppressive treatment.
12. Uncontrolled or active infection with human immunodeficiency virus (HIV), hepatitis B, or hepatitis C infection, or has a diagnosis of immunodeficiency
13. NOTE: Other Exclusion criteria may apply. The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 4

1. Dose escalation part 1A and Japan Cohort F Presence of dose-limiting toxicities (DLTs) in Cycles 1 and 2
2. Dose escalation and Japan Cohort F: Percentage of participants experiencing treatment-emergent adverse events (TEAEs)
3. Dose expansion/optimization: Objective response rate (ORR)
4. Dose escalation part 1B Presence of dose-limiting toxicities (DLTs) in Cycles 1 to 3

Secondary endpoints 13

1. Dose escalation and Japan Cohort F Objective response rate (ORR)
2. Dose escalation, expansion/optimization and Japan Cohort F Duration of response (DoR)
3. Dose escalation, expansion/optimization and Japan Cohort F Assessment of SAR445877 Cmax
4. Dose escalation, expansion/optimization and Japan Cohort F Assessment of SAR445877 AUCtau
5. Dose escalation, expansion/optimization and Japan Cohort F Assessment of SAR445877 Tmax
6. Dose escalation, expansion/optimization in Combination Assessment of combined therapies Ctrough
7. Dose escalation, expansion/optimization and Japan Cohort F Percentage of participants with presence of anti-drug antibodies (ADAs) against SAR445877
8. Dose expansion/optimization Time to response
9. Dose expansion/optimization Clinical Benefit Rate
10. Dose expansion/optimization Progression-free survival
11. Dose expansion/optimization Number of participants with Adverse events (AE)
12. Dose expansion/optimization Overall survival
13. Dose escalation, expansion/optimization Percentage of participants with presence of anti-drug antibodies (ADAs) against ADG126

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 4

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Sanofi-Aventis Recherche & Developpement

Sponsor organisation

Sanofi-Aventis Recherche & Developpement

Address

82 Avenue Raspail

City

Gentilly

Postcode

94250

Country

France

Scientific contact point

Organisation

Sanofi-Aventis Research & Development

Contact name

Clinical Sciences and Operations

Public contact point

Organisation

Sanofi-Aventis Research & Development

Contact name

Clinical Sciences and Operations

Third parties 10

Locations

2 EU/EEA countries · 4 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 21 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

6 submissions — initial application plus substantial / non-substantial modifications