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A Study of SAR444245 Combined With Other Anticancer Therapies for the Treatment of Participants With Lung Cancer or Mesothelioma (Pegathor Lung 202)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04914897
Recruitment Status : Active, not recruiting
First Posted : June 7, 2021
Last Update Posted : February 15, 2023
Sponsor:
Collaborator:
Merck Sharp & Dohme LLC
Information provided by (Responsible Party):
Sanofi

Study Description
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Brief Summary:

Primary Objective:

-To determine the antitumor activity of SAR444245 in combination with other anticancer therapies.

Secondary Objectives:

  • To confirm the dose and to assess the safety profile of SAR444245 when combined with other anticancer therapies.
  • To assess other indicators of antitumor activity.
  • To assess the pharmacokinetic (PK) profile of SAR444245 when given in combination with pembrolizumab.
  • To assess the immunogenicity of SAR444245.

Condition or disease Intervention/treatment Phase
Pleural Mesothelioma Non-small Cell Lung Cancer Drug: THOR-707 Drug: Pembrolizumab Phase 2

Detailed Description:
The duration of the study for an individual patient will start from the signature of the main informed consent and include a screening period of up to 28 days, a treatment period [max 35 cycles {cohorts A1, A2, and B1} = 735 days or until PD {cohort C1}], an end-of-treatment visit at least 30 days following the last administration of study drug (or until the patient receives another anticancer therapy, whichever is earlier), and a follow-up visit 3 months after treatment discontinuation and every 3 months following, until disease progression, or initiation of another antitumor treatment, or death, whichever is earlier
Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 160 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 2 Non-randomized, Open-label, Multi-cohort, Multi-center Study Assessing the Clinical Benefit of SAR444245 (THOR-707) Combined With Other Anticancer Therapies for the Treatment of Participants With Lung Cancer or Pleural Mesothelioma
Actual Study Start Date : September 23, 2021
Estimated Primary Completion Date : July 18, 2023
Estimated Study Completion Date : February 9, 2024

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: Cohort A1: Non-small cell lung cancer 1rst line therapy with Tumor proportion score > 50%
SAR444245 + pembrolizumab, on day 1 of a 21-day treatment cycle (up 35 cycles).
 Drug: THOR-707
Intravenous infusion: solution for infusion

Drug: Pembrolizumab
Intravenous infusion: solution for infusion
Other Name: Keytruda® or generic
Experimental: Cohort A2: Non-small cell lung cancer 1rst line therapy with Tumor proportion score 1-49%
SAR444245 + pembrolizumab, on day 1 of a 21-day treatment cycle (up 35 cycles).
 Drug: THOR-707
Intravenous infusion: solution for infusion

Drug: Pembrolizumab
Intravenous infusion: solution for infusion
Other Name: Keytruda® or generic
Experimental: Cohort B1: Non-small cell lung cancer 2/3rd line therapy
SAR444245 + pembrolizumab, on day 1 of a 21-day treatment cycle (up 35 cycles).
 Drug: THOR-707
Intravenous infusion: solution for infusion

Drug: Pembrolizumab
Intravenous infusion: solution for infusion
Other Name: Keytruda® or generic
Experimental: Cohort C1: :Mesotheloma 2/3rd line therapy
SAR444245 + pembrolizumab, on day 1 of a 21-day treatment cycle (up 35 cycles).
 Drug: THOR-707
Intravenous infusion: solution for infusion

Drug: Pembrolizumab
Intravenous infusion: solution for infusion
Other Name: Keytruda® or generic


Outcome Measures
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Primary Outcome Measures :
  1. Objective response rate (ORR) [ Time Frame: Baseline to the date of first documented progression or initiation of subsequent anticancer therapy or approximatively 9 months after the last participant receive first dose ]
    Objective response rate (ORR), defined as the proportion of participants who have a confirmed complete response (CR) or partial response (PR), derived based on Investigator's assessment per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 for Cohort A1, Cohort A2, and Cohort B1; per modified RECIST (mRECIST) for Cohort C1.


Secondary Outcome Measures :
  1. To confirm the dose [ Time Frame: Observation period is 1 cycle (21 days) ]
    Incidence of Dose-limiting toxicities (DLTs) during DLT observation period

  2. Assessment of SAR444245 safety profile when combined with other anticancer therapies-Treatment Emergent Adverse Events [ Time Frame: From 1st IMP dose up to 30 days after the last dose of IMP ]
    Incidence of Treatment Emergent Adverse Events (TEAEs) and laboratory abnormalities according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) V5.0 and American Society for Transplantation and Cellular Therapy (ASTCT) consensus gradings

  3. Assessment of SAR444245 safety profile when combined with other anticancer therapies-Serious Adverse Events [ Time Frame: From 1st IMP dose up to 90 days after the last dose of IMP ]
    Incidence of Serious Adverse Events (SAEs) and laboratory abnormalities according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) V5.0 and American Society for Transplantation and Cellular Therapy (ASTCT) consensus gradings

  4. Time to response [ Time Frame: From the date of first dose until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 36 months ]
    Time to response (TTR) defined as the time from the first administration of investigational medicinal product (IMP) to the first tumor assessment at which the overall response was recorded as PR or CR that is subsequently confirmed and determined by investigator per RECIST 1.1 (for NSCLC) or mRECIST (for mesothelioma)

  5. Duration of response [ Time Frame: From the date of first dose until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 36 months ]
    Duration of response (DoR), defined as the time from first tumor assessment at which the overall response was recorded as PR or CR that is subsequently confirmed until progressive disease (PD) determined by investigator per RECIST 1.1 (for NSCLC) or mRECIST (for mesothelioma) or death from any cause, whichever occurs first.

  6. Clinical benefit rate [ Time Frame: From the date of first dose until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 36 months ]
    Clinical benefit rate (CBR) including CR or PR at any time plus stable disease (SD) of at least 6 months (per RECIST 1.1 [for NSCLC] or mRECIST [for mesothelioma]).

  7. Progression free survival (PFS) [ Time Frame: From the date of first dose until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 36 months ]
    Progression free survival (PFS), defined as the time from the date of first IMP administration to the date of the first documented disease progression as per RECIST 1.1 for NSCLC) or mRECIST (for mesothelioma) or death due to any cause, whichever occurs first

  8. To assess the plasma concentrations of SAR444245 [ Time Frame: Day 1, Day 2, and Day 3 of Cycle1, at Day 1 of Cycle 2-4-7-10 + every 5th cycle (each cycle is 21 days), maximum is up to approximately 24 months ]
  9. To assess the incidence of anti-drug antibodies (ADAs) against SAR444245. [ Time Frame: Day 1 and Day 8 of Cycle1, Day 1 of Cycle 2-4-7-10 + every 5th cycle (each cycle is 21 days) and 30 days after last IMP administration, maximum is up to approximately 24 months ]

Eligibility Criteria
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Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Participant must be ≥18 years of age (or country's legal age of majority if >18 years), at the time of signing the informed consent.
  • Histologically or cytologically confirmed diagnosis of Stage IV NSCLC (cohorts A1, A2, and B1), or unresectable malignant pleural mesothelioma (cohort C1).
  • Cohort A1: PD-L1 expression TPS ≥ 50%
  • Cohort A2: PD-L1 expression TPS 1 - 49%
  • Prior anticancer therapy
  • Cohorts A1 and A2: No prior systemic therapy for advanced/metastatic NSCLC. Participants who received adjuvant or neoadjuvant therapy are eligible if the adjuvant/neoadjuvant therapy was completed at least 6 months prior to the development of metastatic disease.
  • Cohort B1: One prior anti-PD1/PD-L1 regimen (may include chemotherapy) plus one additional chemotherapy regimen
  • Cohort C1: One or two prior systemic treatments that include pemetrexed-based regimen in combination with platinum agent.
  • All cohorts must have a measurable disease
  • Mandatory baseline biopsy for the first 20 participants to enroll in cohorts A1, A2
  • Cohort B1: Based on the Investigator's judgment, either docetaxel or pemetrexed is not the best treatment option for the participant.

  • Females are eligible to participate if they are not pregnant or breastfeeding, not a woman of childbearing potential (WOCBP) or are a WOCBP that agrees:

    • to use approved contraception method and submit to regular pregnancy testing prior to treatment and for 150 days after discontinuing study treatment
    • to refrain from donating or cryopreserving eggs for 150 days after discontinuing study treatment.
  • Males are eligible to participate if they agree to refrain from donating or cryopreserving sperm, and either abstain from heterosexual intercourse OR use approved contraception during study treatment and for at least 210 days after discontinuing study treatment.
  • Capable of giving signed informed consent.

Exclusion Criteria:

Participants are excluded from the study if any of the following criteria apply:

  • Eastern Cooperative Oncology Group (ECOG) performance status of ≥ 2.
  • Poor bone marrow reserve
  • Poor organ function
  • Participants with baseline SpO2 ≤ 92%.
  • Active brain metastases or leptomeningeal disease.
  • History of allogenic tissue/solid organ transplant
  • Last administration of prior antitumor therapy or any investigational treatment within 28 days or less than 5 times the half-life, whichever is shorter; major surgery or local intervention within 28 days.
  • Has received prior IL-2-based anticancer treatment.
  • Comorbidity requiring corticosteroid therapy
  • Antibiotic use (excluding topical antibiotics) ≤14 days prior to first dose of IMP
  • Severe or unstable cardiac condition within 6 months prior to starting study treatment
  • Active, known, or suspected autoimmune disease that has required systemic treatment in the past 2 years
  • Known second malignancy either progressing or requiring active treatment within the last 3 years
  • Cohorts A1, A2, and C1: Prior treatment with an agent (approved or investigational) that blocks the PD1/PD-L1 pathway (participants who joined a study with an anti-PD1/PD-L1 but have written confirmation they were on control arm are allowed).
  • Receipt of a live-virus vaccination within 28 days of planned treatment start. Seasonal flu vaccines that do not contain live virus are permitted.

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

Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04914897


Locations
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Sponsors and Collaborators
Sanofi
Merck Sharp & Dohme LLC
More Information
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Responsible Party: Sanofi
ClinicalTrials.gov Identifier: NCT04914897    
Other Study ID Numbers: ACT16849
U1111-1254-0107 ( Registry Identifier: ICTRP )
2020-005331-78 ( EudraCT Number )
Merck MK3475-B71 ( Other Identifier: Merck Sharp & Dohme Corp. )
First Posted: June 7, 2021    Key Record Dates
Last Update Posted: February 15, 2023
Last Verified: February 2023
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Lung Neoplasms
Mesothelioma
Mesothelioma, Malignant
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
 Adenoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms, Mesothelial
Pleural Neoplasms
Pembrolizumab
Antineoplastic Agents, Immunological
Antineoplastic Agents