Dose Escalation and Expansion Study of SAR443216 in Participants With Relapsed/Refractory HER2 Expressing Solid Tumors

Sponsor
Sanofi (Industry)
Overall Status
Recruiting
CT.gov ID
NCT05013554
Collaborator
(none)
184
8
5
50.5
23
0.5

Study Details

Study Description

Brief Summary

Primary Objectives:

Part 1 (Dose Escalation)

  • To determine the MTD/maximum administered dose (MAD) of SAR443216 administered as a single agent in participants with HER2 expressing solid tumors and determine the RP2D in the dose escalation part.

  • To determine the maximum lead-in dose and the recommended target dose for phase 2.

  • To determine the safety of SAR443216

Part 2 (Dose expansion)

-To assess preliminary clinical activity of single agent SAR4443216 at the RP2D in participants with HER2 expressing solid tumors, with various levels of HER2 expression.

Secondary Objectives:

Part 1

-To assess preliminary clinical activity of single agent SAR443216 at the R2PD in participants with HER2 expressing solid tumors, with various levels of HER2 expression.

Part 2

-To determine the safety of SAR443216

Part 1 and 2

  • To characterize the pharmacokinetic (PK) profile of SAR443216 when administered as a single agent

  • To evaluate the immunogenicity of SAR443216

Condition or Disease Intervention/Treatment Phase
Phase 1

Detailed Description

The expected duration of study intervention for participants may vary, based on progression date; median expected duration of study per participant is estimated to be:

  • 7.5 months (up to 1 month for screening, a median of 3.5 months for treatment, and a median of 3 months for long term follow-up) in escalation.

  • 9.5 months (up to 1 month for screening, a median of 5.5 months for treatment, and a median of 3 months for long term follow-up) in expansion.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
184 participants
Allocation:
Non-Randomized
Intervention Model:
Sequential Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase 1/1b Open-label, First-in-human, Single Agent, Dose Escalation and Expansion Study for the Evaluation of Safety, Pharmacokinetics, Pharmacodynamics, and Anti-tumor Activity of SAR443216 in Participants With Relapsed/Refractory HER2 Expressing Solid Tumors.
Actual Study Start Date :
Aug 23, 2021
Anticipated Primary Completion Date :
Nov 7, 2025
Anticipated Study Completion Date :
Nov 7, 2025

Arms and Interventions

Arm Intervention/Treatment
Experimental: SAR443216-Dose Escalation

Participants with metastatic solid tumors that express HER2 in tumor tissue and/or with HER2 aberration will receive an IV infusion administration of SAR443216

Drug: SAR443216
Solution for infusion: IV infusion

Experimental: SAR443216-Dose Expansion - metastatic breast cancers with HER2 high expression: Cohort A

Participants with metastatic breast cancers with HER2 high expression will receive an IV infusion administration of SAR443216

Drug: SAR443216
Solution for infusion: IV infusion

Experimental: SAR443216-Dose Expansion- metastatic breast cancers with HER2 low expression: Cohort B

Participants with metastatic breast cancers with HER2 low expression or HER2 mutation (without amplification) will receive an IV infusion administration of SAR443216

Drug: SAR443216
Solution for infusion: IV infusion

Experimental: SAR443216-Dose Expansion- metastatic gastric cancers with HER2 low expression: Cohort C

Participants with metastatic gastric cancers with HER2 low expression or HER2 mutation (without amplification) will receive an IV infusion administration of SAR443216

Drug: SAR443216
Solution for infusion: IV infusion

Experimental: SAR443216-Dose Expansion - metastatic NSCLC with HER2 low or high expression: Cohort D

Participants with metastatic NSCLC with HER2 low or high expression and/or HER2 mutation will receive an IV infusion administration of SAR443216

Drug: SAR443216
Solution for infusion: IV infusion

Outcome Measures

Primary Outcome Measures

  1. Part 1: Dose Escalation Determine the MTD/maximum administered dose (MAD) and RP2D of SAR443216 [Cycle 1, cycle duration is 28 days]

    Incidence of study dose limiting toxicities (DLTs)

  2. Part 1: Dose Escalation: Assessment of Adverse events (AEs) [Baseline until end of study, up to approximately 7.5 months]

    Incidence of treatment emergent adverse events (TEAEs) and serious adverse events (SAEs) according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0.

  3. Part 2: Dose Expansion Objective response rate (ORR) of SAR443216 in all participants [From date of enrollment until the end of treatment, up to approximately 9.5 months]

    Objective response rate is defined as the proportion of participants who achieve a complete response (CR) or partial response (PR) per RECIST v1.1.

  4. Part 2: Dose Expansion Duration of response (DoR) of SAR443216 in all participants. [From date of enrollment until the end of treatment, up to approximately 9.5 months]

    Duration of response per RECIST v1.1 is defined as the interval from the first documentation of CR or PR to the earlier of the first documentation of definitive disease progression or death due to any cause, whichever occurs first.

Secondary Outcome Measures

  1. Part 1: Objective response rate (ORR) of SAR443216 in all participants [From date of enrollment until the end of treatment, up to approximately 7.5 months]

    Objective response rate is defined as the proportion of participants who achieve a complete response (CR) or partial response (PR) per RECIST v1.1.

  2. Part 1: Duration of response (DoR) of SAR443216 in all participants. [From date of enrollment until the end of treatment, up to approximately 7.5 months]

    Duration of response per RECIST v1.1 is defined as the interval from the first documentation of CR or PR to the earlier of the first documentation of definitive disease progression or death due to any cause, whichever occurs first

  3. Part 1: Progression Free Survival (PFS) [From date of enrollment until the end of treatment, up to approximately 7.5 months]

    Progression free survival (PFS) will be assessed by the Investigator per RECIST v1.1 and will be summarized using the Kaplan-Meier method

  4. Part 2: Assessment of TEAEs and SAEs [Baseline until the end of the study, up to approximately 9.5 months]

    Number of participants with treatment emergent adverse events (TEAEs) and serious adverse events (SAEs) according to NCI CTCAE Version 5.0

  5. Part 1 and Part 2: Pharmacokinetic Parameter: Cmax of SAR443216 [From date of enrollment until the end of treatment, up to approximately 7.5 months for Part 1 and 9.5 months for Part 2]

    Maximum observed plasma concentration

  6. Part 1 and Part 2: Pharmacokinetic Parameter: Ctrough of SAR443216 [From date of enrollment until the end of treatment, up to approximately 7.5 months for Part 1 and 9.5 months for Part 2]

    Plasma concentration observed just before treatment administration during repeated dosing

  7. Part 1 and Part 2: Pharmacokinetic Parameter: t 1/2z of SAR443216 [From date of enrollment until the end of treatment, up to approximately 7.5 months for Part 1 and 9.5 months for Part 2]

    Terminal half-life associated with the terminal slope (λz)

  8. Part 1 and Part 2: Pharmacokinetic Parameter: AUC0-τ of SAR443216 [From date of enrollment until the end of treatment, up to approximately 7.5 months for Part 1 and 9.5 months for Part 2]

    Area under the plasma concentration versus time curve

  9. Part 1 and Part 2: Evaluation of SAR443216 immunogenicity [From date of enrollment until the end of treatment, up to approximately 7.5 months for Part 1 and 9.5 months for Part 2]

    Incidence of ADA induction and ADA persistence

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
  • Participants must be ≥ 18 years of age

  • Histologically proven diagnosis of advanced solid tumors

  • Eastern Cooperative Oncology Group (ECOG) performance status 0-1

  • Participants must have HER2 expression in tumor tissue and/or with HER2 aberration detected in tumor or blood by means of validated assay (s)

  • Body weight within [45 - 150 kg] (inclusive)

  • Male and female participants including woman of childbearing potential must agree to follow contraceptive guidance

  • Capable of giving signed informed consent

Exclusion Criteria:
  • Any clinically significant cardiac disease

  • History of or current interstitial lung disease or pneumonitis

  • Uncontrolled or unresolved acute renal failure

  • Prior solid organ or hematologic transplant.

  • Known positivity with human immunodeficiency virus (HIV), known active hepatitis A, B, and C, or uncontrolled chronic or ongoing infectious requiring parenteral treatment.

  • Receipt of a live-virus vaccination within 28 days of planned treatment start

  • Participation in a concurrent clinical study in the treatment period.

  • Inadequate hematologic, hepatic and renal function

  • Participant not suitable for participation, whatever the reason, as judged by the Investigator, including medical or clinical conditions.

The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Contacts and Locations

Locations

Site City State Country Postal Code
1 ~University of Texas - MD Anderson Cancer Center-Site Number:8400002 Houston Texas United States 77030
2 Investigational Site Number :4100001 Seoul Seoul-teukbyeolsi Korea, Republic of 03080
3 Investigational Site Number :4100002 Seoul Seoul-teukbyeolsi Korea, Republic of 05505
4 Investigational Site Number :7240003 Barcelona Barcelona [Barcelona] Spain 08035
5 Investigational Site Number :7240002 Madrid / Madrid Madrid, Comunidad De Spain 28050
6 Investigational Site Number :7240001 Madrid Madrid, Comunidad De Spain 28040
7 Investigational Site Number :1580001 Taichung City Taiwan 404
8 Investigational Site Number :1580002 Tainan Taiwan 704

Sponsors and Collaborators

  • Sanofi

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
Sanofi
ClinicalTrials.gov Identifier:
NCT05013554
Other Study ID Numbers:
  • TED16925
  • U1111-1253-2233
  • 2021-000086-32
First Posted:
Aug 19, 2021
Last Update Posted:
Jul 14, 2022
Last Verified:
Jul 13, 2022
Individual Participant Data (IPD) Sharing Statement:
Yes
Plan to Share IPD:
Yes
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Product Manufactured in and Exported from the U.S.:
No
Additional relevant MeSH terms:

Study Results

No Results Posted as of Jul 14, 2022