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A First-in-human, Dose Escalation and Dose Expansion Study of SAR445877 in Adult Participants With Advanced Solid Tumors

ConditionSolid Tumor
Trial statusRecruiting
Trial phasePhase 1, Phase 2
Trial typeInterventional
Biological sexAll
Age18+
SponsorSanofi

About this trial

This is a Phase 1/2, open label, multiple cohort study to assess the safety and preliminary efficacy of SAR445877 as a monotherapy or in combination with other anticancer therapies for participants aged at least 18 years with advanced unresectable or metastatic solid tumors.

The study will include 2 parts:

A dose escalation Part 1: for finding the therapeutic dose(s) of SAR445877 in a monotherapy given every 2 weeks (Q2W) or weekly (QW) and in combination with other anticancer therapies when applicable.

A multicohort dose expansion/dose optimization Part 2: for the assessment of safety and preliminary efficacy of SAR445877 in monotherapy and in combination with cetuximab or with next generation aCTLA4 (ADG126) or with bevacizumab. 2 recommended doses for expansion/optimization of SAR445877 identified from dose escalation part 1 will be tested in different indications in monotherapy and in combination with other anticancer therapies as applicable.

Approximately 542 participants will be exposed to the study intervention:

* approximately 123 participants in part 1, * up to 410 participants in expansion/dose optimization part (part 2) * and up to 9 participants in Japan cohort F.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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

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.

Disqualifiers

Eastern Cooperative Oncology Group (ECOG) performance status of ≥2

Predicted life expectancy ≤3 months

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.

Diagnosed of any other malignancies, either progressing or requiring active treatments, within 2 years prior to enrollment

Trial design

Design model

Sequential

Treatments tested in this trial

  • SAR445877

    Drug

    Concentrate for solution for infusion

  • Cetuximab

    Drug

    Solution for infusion

  • ADG126

    Drug

    Solution for infusion

  • Bevacizumab

    Drug

    Solution for infusion

  • Nivolumab

    Drug

    Solution for infusion

  • Ipilimumab

    Drug

    Solution for infusion

Treatment groups

542 Participants
are divided into 18 treatment groups

18

Treatment groups

See each treatment group below.

Group A: SAR445877 Escalation Phase (Part 1A)Experimental treatment 1 intervention
Group B: SAR445877 Escalation Phase (Part1B)Experimental treatment 2 interventions
Group C: SAR445877 Escalation Phase (Part 1C)Experimental treatment 2 interventions
Group D: SAR445877 Expansion/Optimization Phase: Cohort A1 (Part 2A)Experimental treatment 1 intervention
Group E: SAR445877 Expansion/Optimization Phase: Cohort A2 (Part 2A)Experimental treatment 1 intervention
Group F: SAR445877 Expansion/Optimization Phase: Cohort B (Part 2A)Experimental treatment 1 intervention
Group G: SAR445877 Expansion/Optimization Phase: Cohort C1 (Part 2A)Experimental treatment 1 intervention
Group H: SAR445877 Expansion/Optimization Phase: Cohort C2 (Part 2A)Experimental treatment 1 intervention
Group I: SAR445877 Expansion/Optimization Phase: Cohort D (Part 2A)Experimental treatment 1 intervention
Group J: SAR445877 Expansion/Optimization Phase: Cohort E1 (Part 2B)Experimental treatment 1 intervention
Group K: SAR445877 Expansion/optimization Phase: Cohort E2 (Part 2A)Experimental treatment 1 intervention
Group L: SAR445877 Expansion/optimization Phase: Cohort E3 (Part 2B)Experimental treatment 2 interventions
Group M: SAR445877 Japan Cohort FExperimental treatment 1 intervention
Group N: SAR445877 Expansion/Optimization Phase Cohort G1 (Part 2C)Experimental treatment 2 interventions
Group O: SAR445877 Expansion/Optimization Phase Cohort G2 (Part 2C)Experimental treatment 2 interventions
Group P: SAR445877 Expansion/Optimization Phase Cohort G3 (Part 2C)Experimental treatment 2 interventions
Group Q: SAR445877 Expansion/Optimization Phase Cohort H1 (Part 2D)Experimental treatment 2 interventions
Group R: SAR445877 Expansion/Optimization Phase Cohort H2 (Part 2D)Experimental treatment 2 interventions

Trial outcomes

Primary outcomes

1

Dose escalation part 1A, 1C and Japan Cohort F: Presence of dose-limiting toxicities (DLTs) in Cycles 1 and 2

DLTs will be defined using NCI CTCAE version 5.0 or ASTCT criteria for CRS or immune effector cell-associated neurotoxicity syndrome (ICANS)

Time frame
Cycles 1 & 2 - 14 days per cycle
2

Dose escalation part 1B: Presence of dose-limiting toxicities (DLTs) in Cycle 1 to 3 in part B

Time frame
Cycle 1 to 3 -14 days per cycle
3

Dose escalation and Japan Cohort F: Percentage of participants experiencing treatment-emergent adverse events (TEAEs)

Presence of TEAEs, SAEs, and lab abnormalities, according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 and American Society for Transplantation and Cellular Therapy (ASTCT) consensus grading

Time frame
The time from the first dose of study interventions up to 30 days after last dose of study interventions
4

Dose expansion/optimization: Objective response rate (ORR)

Proportion of participants who have a confirmed complete response (CR) or a partial response (PR), as the best overall response (BOR) determined by the Investigator as per the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1

Time frame
From baseline to the end of dose expansion/optimization (up to 2 years)

Secondary outcomes

1

Dose escalation and Japan Cohort F: Objective response rate (ORR)

Proportion of participants who have a confirmed complete response (CR) or a partial response (PR), as the best overall response (BOR) determined by the Investigator as per the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1

Time frame
From baseline to the end of dose escalation (up to 2 years)
2

Dose escalation, expansion/optimization and Japan Cohort F: Duration of response (DoR)

DoR is defined as the time from first documented evidence of confirmed CR or PR until progressive disease (PD) determined by Investigator per RECIST 1.1 or death from any cause, whichever occurs first

Time frame
From baseline to the end of study (up to 2 years)
3

Dose escalation, expansion/optimization and Japan Cohort F: Assessment of SAR445877 Cmax

Maximum plasma concentration observed

Time frame
Cycle 1 Day 1 to Day 8 or Day 14 (cycle duration of 14 days)
4

Dose escalation, expansion/optimization and Japan Cohort F: Assessment of SAR445877 AUCtau

Area under the concentration versus time curve calculated using the trapezoidal method during a dosing interval (T)

Time frame
Cycle 1 Day 1 to Day 8 or Day 14 (cycle duration of 14 days)

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Sanofi

Lead sponsor

Source ClinicalTrials.gov
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