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

NCT04914897 | Terminated Phase 2 Results DMC FDA Drug

• 5 other identifiers: ACT16849U1111-1254-0107MK-3475-B71KEYNOTE-B712020-005331-78
• Study Type: interventional
• Target: 106
• Locations: 11 countries
• Sites: 35

Brief Summary

The Primary Objective was:

• To determine the antitumor activity of SAR444245 in combination with other anticancer therapies. The Secondary Objectives were:
• 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.

Conditions

Pleural Mesothelioma; Non-small Cell Lung Cancer

Outcome Measures

Primary Outcomes (3)

• Cohorts A1 and A2: Objective Response Rate (ORR)

  ORR was defined as the percentage of participants who had a confirmed complete response (CR) or partial response (PR) as per Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1. CR. CR was defined as the disappearance of all target lesions, any pathological lymph nodes (whether target or non-target) with reduction in short axis to \<10 millimeter (mm) (\<1 centimeter \[cm\]). PR was defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.

  From first dose of study treatment administration (Day 1) up to approximately 21 months

• Cohorts B1: Objective Response Rate

  ORR was defined as the percentage of participants who had a confirmed CR or PR as per RECIST v1.1. CR was defined as the disappearance of all target lesions, any pathological lymph nodes (whether target or non-target) with reduction in short axis to \<10 mm (\<1 cm). PR was defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.

  From first dose of study treatment administration (Day 1) up to maximum exposure of study treatment; approximately 14 months

• Cohorts C1: Objective Response Rate

  ORR was defined as the percentage of participants who had a confirmed CR or PR assessed by the investigator as per modified RECIST (mRECIST) v1.1. CR. CR was defined as the disappearance of all target lesions, any pathological lymph nodes (whether target or non-target) with reduction in short axis to \<10 mm (\<1 cm). PR was defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.

  From first dose of study treatment administration (Day 1) up to approximately 21 months

Secondary Outcomes (9)

• All Cohorts: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs)

  From first dose of study treatment (Day 1) up to 30 days after the last dose of study treatment; approximately 28 months (Cohorts A1 and A2), 15 months (Cohort B1), and 25 months (Cohort C1)

• All Cohorts: Number of Participants With Dose Limiting Toxicities (DLTs)

  From Day 1 to Day 21 of Cycle 1 (each cycle is 21 days)

• All Cohorts: Time to Response (TTR)

  From first dose of study treatment administration (Day 1) up to maximum exposure of study treatment; approximately 27 months (Cohorts A1 and A2), 14 months (Cohort B1), and 24 months (Cohort C1)

• All Cohorts: Duration of Response (DOR)

  From first dose of study treatment administration (Day 1) up to maximum exposure of study treatment; approximately 27 months (Cohorts A1 and A2), 14 months (Cohort B1), and 24 months (Cohort C1)

• All Cohorts: Clinical Benefit Rate (CBR)

  From first dose of study treatment administration (Day 1) up to maximum exposure of study treatment; approximately 27 months (Cohorts A1 and A2), 14 months (Cohort B1), and 24 months (Cohort C1)

Study Arms (4)

Cohort A1: NSCLC, PD-L1 TPS >=50%:Pegenzileukin 24 μg/kg + Pembrolizumab as 1L Therapy

EXPERIMENTAL

Participants with previously untreated Stage IV non-small cell lung cancer (NSCLC) and programmed cell death-ligand 1 (PD-L1) tumor proportion score (TPS) of \>=50% were included in this cohort. Participants received pegenzileukin 24 microgram per kilogram (μg/kg) along with pembrolizumab 200 milligram (mg) via intravenous (IV) infusion over 30 minutes every 3 weeks (q3w) on Day 1 of each cycle (each cycle is 21 days) (as first-line \[1L\] therapy), until disease progression (PD), unacceptable adverse event (AE) or other full permanent discontinuation criteria was met or completion of Cycle 35.

Drug: THOR-707; Drug: Pembrolizumab

Cohort A2: NSCLC, PD-L1 TPS 1%-49%:Pegenzileukin 24 μg/kg+Pembrolizumab as 1L Therapy

EXPERIMENTAL

Participants with previously untreated Stage IV NSCLC and PD-L1 TPS of 1%-49% were included in this cohort. Participants received pegenzileukin 24 μg/kg along with pembrolizumab 200 mg via IV infusion over 30 minutes q3w on Day 1 of each cycle (each cycle is 21 days) (as 1L therapy), until PD, unacceptable AE or other full permanent discontinuation criteria was met or completion of Cycle 35.

Drug: THOR-707; Drug: Pembrolizumab

Cohort B1: NSCLC:Pegenzileukin 24 μg/kg+Pembrolizumab as 2/3L Therapy

EXPERIMENTAL

Participants with NSCLC for whom standard of care (SOC) was not in their best interest or where no SOC was established were included in this cohort. Participants received pegenzileukin 24 μg/kg along with pembrolizumab 200 mg via IV infusion over 30 minutes q3w on Day 1 of each cycle (each cycle is 21 days) (as second-line or third-line \[2/3L\] therapy), until PD, unacceptable AE or other full permanent discontinuation criteria was met or completion of Cycle 35.

Drug: THOR-707; Drug: Pembrolizumab

Cohort C1: Mesothelioma: Pegenzileukin 24 μg /kg+Pembrolizumab as 2/3L Therapy

EXPERIMENTAL

Participants with mesothelioma who had no SOC established and had experienced PD during or after at least one but no more than 2 prior regimens were included in this cohort. Participants received pegenzileukin 24 μg/kg along with pembrolizumab 200 mg via IV infusion over 30 minutes q3w on Day 1 of each cycle (each cycle is 21 days) (as 2/3L therapy), until PD, unacceptable AE or other full permanent discontinuation criteria was met or completion of Cycle 35.

Drug: THOR-707; Drug: Pembrolizumab

Interventions

THOR-707 DRUG

Intravenous infusion: solution for infusion

Also known as: Pegenzileukin

Cohort A1: NSCLC, PD-L1 TPS >=50%:Pegenzileukin 24 μg/kg + Pembrolizumab as 1L Therapy; Cohort A2: NSCLC, PD-L1 TPS 1%-49%:Pegenzileukin 24 μg/kg+Pembrolizumab as 1L Therapy; Cohort B1: NSCLC:Pegenzileukin 24 μg/kg+Pembrolizumab as 2/3L Therapy; Cohort C1: Mesothelioma: Pegenzileukin 24 μg /kg+Pembrolizumab as 2/3L Therapy

Pembrolizumab DRUG

Intravenous infusion: solution for infusion

Also known as: KEYTRUDA® or generic

Cohort A1: NSCLC, PD-L1 TPS >=50%:Pegenzileukin 24 μg/kg + Pembrolizumab as 1L Therapy; Cohort A2: NSCLC, PD-L1 TPS 1%-49%:Pegenzileukin 24 μg/kg+Pembrolizumab as 1L Therapy; Cohort B1: NSCLC:Pegenzileukin 24 μg/kg+Pembrolizumab as 2/3L Therapy; Cohort C1: Mesothelioma: Pegenzileukin 24 μg /kg+Pembrolizumab as 2/3L Therapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participant must have been ≥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 had 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 were eligible to participate if they were 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 were 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.

You may not qualify if:

• Participants were excluded from the study if any of the following criteria applied:
• 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).

Sponsors & Collaborators

• Sanofi: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (35)

Thomas Jefferson University Hospital Site Number : 8400009

Philadelphia, Pennsylvania, 19107, United States

Location

Thomas Jefferson University - North East Site Number : 8401009

Philadelphia, Pennsylvania, 19114, United States

Location

Investigational Site Number : 0320002

CABA, Buenos Aires, 1430, Argentina

Location

Investigational Site Number : 0360002

Richmond, Victoria, 3121, Australia

Location

Investigational Site Number : 1520005

Santaigo, Reg Metropolitana de Santiago, 8241470, Chile

Location

Investigational Site Number : 1520004

Santiago, Reg Metropolitana de Santiago, 7500713, Chile

Location

Investigational Site Number : 1520002

Santiago, Reg Metropolitana de Santiago, 7500921, Chile

Location

Investigational Site Number : 1520001

Santiago, Reg Metropolitana de Santiago, 8420383, Chile

Location

Investigational Site Number : 1520003

Temuco, 4800827, Chile

Location

Investigational Site Number : 2500006

Bordeaux, France

Location

Investigational Site Number : 2500005

Paris, 75018, France

Location

Investigational Site Number : 2500001

Saint-Herblain, 44800, France

Location

Investigational Site Number : 2500003

Toulouse, 31059, France

Location

Investigational Site Number : 3800005

Aviano (PN), Friuli Venezia Giulia, 33081, Italy

Location

Investigational Site Number : 3800001

Rozzano, Milano, 20089, Italy

Location

Investigational Site Number : 3800002

Orbassano, Torino, 10043, Italy

Location

Investigational Site Number : 3800006

Bologna, 40138, Italy

Location

Investigational Site Number : 3800004

Milan, 20133, Italy

Location

Investigational Site Number : 3800008

Padua, 35128, Italy

Location

Investigational Site Number : 3920001

Sapporo, Hokkaido, 003-0804, Japan

Location

Investigational Site Number : 6160002

Poznan, Greater Poland Voivodeship, 60-693, Poland

Location

Investigational Site Number : 6160001

Warsaw, Masovian Voivodeship, 02-781, Poland

Location

Investigational Site Number : 6160003

Gdansk, Pomeranian Voivodeship, 80-214, Poland

Location

Investigational Site Number : 6160004

Olsztyn, Warmian-Masurian Voivodeship, 10-357, Poland

Location

Investigational Site Number : 4100002

Seoul, Seoul-teukbyeolsi, 03080, South Korea

Location

Investigational Site Number : 4100003

Seoul, Seoul-teukbyeolsi, 05505, South Korea

Location

Investigational Site Number : 4100001

Seoul, Seoul-teukbyeolsi, 06351, South Korea

Location

Investigational Site Number : 7240006

Barcelona, Barcelona [Barcelona], 08035, Spain

Location

Investigational Site Number : 7240003

Girona, Girona [Gerona], 17007, Spain

Location

Investigational Site Number : 7240004

Madrid, Madrid, Comunidad de, 28046, Spain

Location

Investigational Site Number : 7240002

Madrid, 28034, Spain

Location

Investigational Site Number : 7240001

Madrid, 28041, Spain

Location

Investigational Site Number : 1580003

Taichung, 404, Taiwan

Location

Investigational Site Number : 1580002

Tainan, 704, Taiwan

Location

Investigational Site Number : 1580005

Taipei, Taiwan

Location

Related Links

• ACT16849 Plain Language Results Summary

MeSH Terms

Conditions

Mesothelioma, Malignant; Carcinoma, Non-Small-Cell Lung

Interventions

pembrolizumab; Drugs, Generic

Condition Hierarchy (Ancestors)

Mesothelioma; Adenoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Mesothelial; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Pleural Neoplasms; Lung Diseases; Respiratory Tract Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms

Intervention Hierarchy (Ancestors)

Pharmaceutical Preparations

Limitations and Caveats

The study was terminated based on strategic sponsor decision not driven by any safety concerns.

Results Point of Contact

• Title: Trial Transparency Team
• Organization: Sanofi aventis recherche & développement

Contact-US@sanofi.com

800-633-1610

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 28, 2021
• First Posted: June 7, 2021
• Study Start: September 23, 2021
• Primary Completion: July 18, 2023
• Study Completion: October 17, 2024
• Last Updated: October 2, 2025
• Results First Posted: October 2, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will share

Locations

AR (1); FR (4); KR (3); TW (3); AU (1); CL (5); JP (1); PL (4); US (2); IT (6); ES (5)