KD050 for Advanced solid tumors | Non-small cell lung cancer | Hepatocellular carcinoma | Gastric cancer | Gastroesophageal junction adenocarcinoma | Colorectal cancer | Melanoma | Renal cell carcinoma | Malignant pleural mesothelioma | Esophageal squamous cell carcinoma

Inclusion criteria

• {"criterion_text":"- 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\n- 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.\n- 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.\n- Capable of giving signed informed consent.\n- 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.\n- 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.\n- 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.\n- 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.\n- 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.\n- 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.\n- 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)\n- 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.\n- 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).\n- 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.\n- 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.\n- 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.\n- Measurable Disease: At least 1 measurable lesion per RECIST 1.1 criteria.\n- 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.\n- 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.\n- 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.\n- 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.\n- 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.\n- Dose expansion/optimization Part 2 Cancer diagnosis: Part 2C Cohorts G1, G2 and G3: Participants with histologically confirmed unresectable locally advanced or metastatic melanoma"}

Exclusion criteria

• {"criterion_text":"- Eastern Cooperative Oncology Group (ECOG) performance status of ≥2.\n- 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.\n- Organ transplant requiring immunosuppressive treatment.\n- Uncontrolled or active infection with human immunodeficiency virus (HIV), hepatitis B, or hepatitis C infection, or has a diagnosis of immunodeficiency\n- 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.\n- Predicted life expectancy ≤3 months.\n- 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.\n- Diagnosed of any other malignancies, either progressing or requiring active treatments, within 2 years prior to enrollment.\n- Known active brain metastases or leptomeningeal metastases.\n- 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.\n- 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.\n- Any clinically significant cardiac (including valvular) or vascular (thromboembolic disorders) disease, within 6 months prior to the first IMP administration.\n- 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."}

Primary endpoints

• {"endpoint_text":"- Dose escalation part 1A and Japan Cohort F Presence of dose-limiting toxicities (DLTs) in Cycles 1 and 2","definition_or_measurement_approach":"Assessment of presence of dose-limiting toxicities (DLTs) occurring during Cycles 1 and 2"}
• {"endpoint_text":"- Dose escalation and Japan Cohort F: Percentage of participants experiencing treatment-emergent adverse events (TEAEs)","definition_or_measurement_approach":"Proportion (%) of participants experiencing treatment-emergent adverse events"}
• {"endpoint_text":"- Dose expansion/optimization: Objective response rate (ORR)","definition_or_measurement_approach":""}
• {"endpoint_text":"- Dose escalation part 1B Presence of dose-limiting toxicities (DLTs) in Cycles 1 to 3","definition_or_measurement_approach":"Assessment of presence of dose-limiting toxicities (DLTs) occurring during Cycles 1 to 3"}

Secondary endpoints

• {"endpoint_text":"- Dose escalation and Japan Cohort F Objective response rate (ORR)","definition_or_measurement_approach":""}
• {"endpoint_text":"- Dose escalation, expansion/optimization and Japan Cohort F Duration of response (DoR)","definition_or_measurement_approach":""}
• {"endpoint_text":"- Dose escalation, expansion/optimization and Japan Cohort F Assessment of SAR445877 Cmax","definition_or_measurement_approach":""}
• {"endpoint_text":"- Dose escalation, expansion/optimization and Japan Cohort F Assessment of SAR445877 AUCtau","definition_or_measurement_approach":""}
• {"endpoint_text":"- Dose escalation, expansion/optimization and Japan Cohort F Assessment of SAR445877 Tmax","definition_or_measurement_approach":""}
• {"endpoint_text":"- Dose escalation, expansion/optimization in Combination Assessment of combined therapies Ctrough","definition_or_measurement_approach":""}
• {"endpoint_text":"- Dose escalation, expansion/optimization and Japan Cohort F Percentage of participants with presence of anti-drug antibodies (ADAs) against SAR445877","definition_or_measurement_approach":""}
• {"endpoint_text":"- Dose expansion/optimization Time to response","definition_or_measurement_approach":""}
• {"endpoint_text":"- Dose expansion/optimization Clinical Benefit Rate","definition_or_measurement_approach":""}
• {"endpoint_text":"- Dose expansion/optimization Progression-free survival","definition_or_measurement_approach":""}
• {"endpoint_text":"- Dose expansion/optimization Number of participants with Adverse events (AE)","definition_or_measurement_approach":""}
• {"endpoint_text":"- Dose expansion/optimization Overall survival","definition_or_measurement_approach":""}
• {"endpoint_text":"- Dose escalation, expansion/optimization Percentage of participants with presence of anti-drug antibodies (ADAs) against ADG126","definition_or_measurement_approach":""}

Spain

Earliest CTIS Part Ii Submission Date

10-10-2024

Latest Decision Or Authorization Date

11-02-2026

Processing Time Days

489

Number Of Sites

2

Number Of Participants

86

Netherlands

Earliest CTIS Part Ii Submission Date

10-10-2024

Latest Decision Or Authorization Date

15-05-2026

Processing Time Days

582

Number Of Sites

2

Number Of Participants

61

Primary sponsor

Full Name

Sanofi-Aventis Recherche & Developpement

Organisation Type

Pharmaceutical company

Country Of Registered Address

France

Contract research organisations

Name

PPD Development LP

Responsibilities

Sponsor duties codes: [4]

Name

Pharmaceutical Product Development LLC

Responsibilities

Sponsor duties codes: [4]

Name

Endpoint Clinical Inc.

Responsibilities

Sponsor duties codes: [3]

Name

Navigate Biopharma Services Inc.

Responsibilities

Sponsor duties codes: [4]

Name

Charles River Laboratories Inc.

Responsibilities

Sponsor duties codes: [4]

Third parties

• {"country":"United States","full_name":"PPD Development LP","duties_or_roles":["4"],"organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Charles River Laboratories Inc.","duties_or_roles":["4"],"organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Guardant Health Inc.","duties_or_roles":["4"],"organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"Germany","full_name":"Azenta Germany GmbH","duties_or_roles":["4"],"organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Endpoint Clinical Inc.","duties_or_roles":["3"],"organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Navigate Biopharma Services Inc.","duties_or_roles":["4"],"organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Pharmaceutical Product Development LLC","duties_or_roles":["4"],"organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Medidata Solutions Inc.","duties_or_roles":["6"],"organisation_type":"Non-Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"ESMS Global Limited","duties_or_roles":["15: Centralized 24-Hour Emergency System: eSMS"],"organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"PPD Development LP (Wilmington address)","duties_or_roles":["1","5"],"organisation_type":"Pharmaceutical company"}