Clinical trial NCT04914897: A Study of SAR444245 Combined With Other Anticancer Therapies for the Treatment of Participants With Lung Cancer or Mesothelioma (Pegathor Lung 202)
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Pleural Mesothelioma
Non-small Cell Lung Cancer
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
Collaborators: name: Merck Sharp & Dohme LLC
First posted: 2021-06-07
Enrollment: 106
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Eligibility 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.

Primary outcomes:
measure: Objective response rate (ORR)
timeFrame: 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
Secondary outcomes:
measure: To confirm the dose
timeFrame: Observation period is 1 cycle (21 days)
measure: Assessment of SAR444245 safety profile when combined with other anticancer therapies-Treatment Emergent Adverse Events
timeFrame: From 1st IMP dose up to 30 days after the last dose of IMP
measure: Assessment of SAR444245 safety profile when combined with other anticancer therapies-Serious Adverse Events
timeFrame: From 1st IMP dose up to 90 days after the last dose of IMP
measure: Time to response
timeFrame: 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
measure: Duration of response
timeFrame: 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
measure: Clinical benefit rate
timeFrame: 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
measure: Progression free survival (PFS)
timeFrame: 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
measure: To assess the plasma concentrations of SAR444245
timeFrame: 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
measure: To assess the incidence of anti-drug antibodies (ADAs) against SAR444245.
timeFrame: 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
Other outcomes:
Locations:
city: Philadelphia
country: United States
facility: Thomas Jefferson University Hospital Site Number : 8400009
state: Pennsylvania
city: Philadelphia
country: United States
facility: Thomas Jefferson University - North East Site Number : 8401009
state: Pennsylvania
city: Caba
country: Argentina
facility: Investigational Site Number : 0320002
state: Buenos Aires
city: Richmond
country: Australia
facility: Investigational Site Number : 0360002
state: Victoria
city: Santaigo
country: Chile
facility: Investigational Site Number : 1520005
state: Reg Metropolitana De Santiago
city: Santiago
country: Chile
facility: Investigational Site Number : 1520004
state: Reg Metropolitana De Santiago
city: Santiago
country: Chile
facility: Investigational Site Number : 1520002
state: Reg Metropolitana De Santiago
city: Santiago
country: Chile
facility: Investigational Site Number : 1520001
state: Reg Metropolitana De Santiago
city: Temuco
country: Chile
facility: Investigational Site Number : 1520003
city: Bordeaux Cedex
country: France
facility: Investigational Site Number : 2500006
city: Paris
country: France
facility: Investigational Site Number : 2500005
city: Saint Herblain
country: France
facility: Investigational Site Number : 2500001
city: Toulouse
country: France
facility: Investigational Site Number : 2500003
city: Aviano (PN)
country: Italy
facility: Investigational Site Number : 3800005
state: Friuli-Venezia Giulia
city: Rozzano
country: Italy
facility: Investigational Site Number : 3800001
state: Milano
city: Orbassano
country: Italy
facility: Investigational Site Number : 3800002
state: Torino
city: Bologna
country: Italy
facility: Investigational Site Number : 3800006
city: Milano
country: Italy
facility: Investigational Site Number : 3800004
city: Padova
country: Italy
facility: Investigational Site Number : 3800008
city: Sapporo-shi
country: Japan
facility: Investigational Site Number : 3920001
state: Hokkaido
city: Seoul
country: Korea, Republic of
facility: Investigational Site Number : 4100002
state: Seoul-teukbyeolsi
city: Seoul
country: Korea, Republic of
facility: Investigational Site Number : 4100003
state: Seoul-teukbyeolsi
city: Seoul
country: Korea, Republic of
facility: Investigational Site Number : 4100001
state: Seoul-teukbyeolsi
city: Warszawa
country: Poland
facility: Investigational Site Number : 6160001
state: Mazowieckie
city: Gdansk
country: Poland
facility: Investigational Site Number : 6160003
state: Pomorskie
city: Olsztyn
country: Poland
facility: Investigational Site Number : 6160004
state: Warminsko-mazurskie
city: Poznan
country: Poland
facility: Investigational Site Number : 6160002
state: Wielkopolskie
city: Barcelona
country: Spain
facility: Investigational Site Number : 7240006
state: Barcelona [Barcelona]
city: Girona
country: Spain
facility: Investigational Site Number : 7240003
state: Girona [Gerona]
city: Madrid
country: Spain
facility: Investigational Site Number : 7240004
state: Madrid, Comunidad De
city: Madrid
country: Spain
facility: Investigational Site Number : 7240002
city: Madrid
country: Spain
facility: Investigational Site Number : 7240001
city: Taichung City
country: Taiwan
facility: Investigational Site Number : 1580003
city: Tainan
country: Taiwan
facility: Investigational Site Number : 1580002
city: Taipei
country: Taiwan
facility: Investigational Site Number : 1580005
Study officials:
References: