NCT04914897 - A Study of SAR444245 Combined With Other Anticancer Therapies for the Treatment of Participants With Lung Cancer or Mesothelioma (Pegathor Lung 202) | Crick

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * 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. * Capable of giving signed informed consent. Exclusion Criteria: 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). * 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.

Outcomes

Primary Outcomes

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.

Time frame: 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.

Time frame: 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.

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

Secondary Outcomes

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

An AE was any untoward medical occurrence in a participant or clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. An SAE was any AE that at any dose: resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect or was an important medical event. TEAEs were defined as AEs that developed, worsened (according to the investigator's opinion) or became serious during the TE period.

Time frame: 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)

Selected events that occurred during DLT observation period were considered as DLT unless due to PD or to a cause obviously unrelated to pegenzileukin. Selected events included: grade (G) 4 neutropenia for \>=7 consecutive days, G3 or 4 neutropenia complicated by fever or microbiologically or radiographically documented infection, G3 or 4 thrombocytopenia associated with clinically significant bleeding that required clinical intervention; G3 or above alanine aminotransferase or aspartate aminotransferase in combination with a bilirubin \>2 times upper limit of normal with no evidence of cholestasis or another cause such as viral infection or other drugs;G3 or above vascular leak syndrome, hypotension, and cytokine release syndrome;any other G3; G3 or 4 non-hematologic laboratory value; any death not clearly due to the underlying disease or extraneous causes;any toxicity that required permanent discontinuation of the study treatment(s).

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

All Cohorts: Time to Response (TTR)

TTR was defined as the time from the date of first study treatment administration to the first tumor assessment at which the overall response was recorded as PR or CR that was subsequently confirmed as per RECIST v 1.1 (NSCLC) and assessed by the investigator as per mRECIST v1.1 (mesothelioma). 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.

Time frame: 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)

DOR was defined as time from date of first tumor assessment at which overall response was recorded as CR or PR that was subsequently confirmed to date of first documentation of objective PD before initiation of any post-treatment anti-cancer therapy or death due to any cause, whichever occurred first, as per RECIST v 1.1 (NSCLS) and assessed by investigator as per mRECIST v1.1 (mesothelioma). CR: 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: at least a 30% decrease in sum of diameters of target lesions, taking as reference baseline sum diameters. PD:at least a 20% increase in sum of diameters of target lesions, taking as reference the smallest sum on study (this included baseline sum if that was smallest on study), in addition to relative increase of 20%, sum must have also demonstrated an absolute increase of at least 5 mm (0.5 cm).

All Cohorts: Clinical Benefit Rate (CBR)

The CBR was defined as the percentage of participants with clinical benefit: confirmed CR or PR as best overall response (BOR), or stable disease (SD) that lasted at least 6 months as per RECIST v 1.1 (NSCLS) and assessed by investigator as per mRECIST v1.1 (mesothelioma). CR: 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: at least a 30% decrease in sum of diameters of target lesions, taking as reference baseline sum diameters. BOR was the best response observed from start of the study treatment until PD, death, cut-off date or initiation of post-treatment anticancer therapy, whichever occurred first. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.

All Cohorts: Progression Free Survival (PFS)

The PFS was defined as the time from the date of first study treatment to the date of the first documentation of objective PD, or death due to any cause, whichever occurred first as per RECIST v 1.1 (NSCLS) and assessed by investigator as per mRECIST v1.1 (mesothelioma). PD was defined as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this included the baseline sum if that was the smallest on study), in addition to the relative increase of 20%, the sum must have also demonstrated an absolute increase of at least 5 mm (0.5 cm).

All Cohorts: Plasma Concentrations of Pegenzileukin

Blood samples were collected at specified timepoints for the assessment of plasma concentrations of pegenzileukin. The pharmacokinetic (PK) parameters were calculated using non-compartmental method.

Time frame: Days 2 and 3 of Cycle 1 (each cycle is 21 days)

All Cohorts: Concentration at End of Infusion (Ceoi) of Pegenzileukin

Blood samples were collected at specified timepoints for the assessment of Ceoi of pegenzileukin.

Time frame: Cycles 1, 2, 4, 7, 10, and 15 (each cycle is 21 days)

All Cohorts: Number of Participants With Anti-Drug Antibodies (ADAs) Against Pegenzileukin

Blood samples were collected at specified timepoints to assess the presence of ADAs against pegenzileukin. Treatment-emergent ADA was defined as at least one treatment-induced or treatment-boosted ADA. Treatment-induced ADA was defined as ADA that developed during the TE period and without pre-existing ADA (including participants without pre-treatment samples). Treatment-boosted ADA was defined as pre-existing ADA that was boosted during the TE period to a significant higher titer than the baseline. Number of participants with treatment-emergent ADA is presented.

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

Overview

Conditions

Interventions

Eligibility

Locations (35)

Outcomes

Primary Outcomes

Secondary Outcomes