An Open Label, Multicenter, Phase Ib/IIa Study to Evaluate Efficacy, Safety, Tolerability, and Pharmacokinetics of the ATR Inhibitor M1774 in Combination With Cemiplimab in Participants With Non-Squamous Non-Small Cell Lung Cancer That Has Progressed on Prior Anti-PD-(L)1 and Platinum-based Therapies (DDRiver NSCLC 322)

Study Identifier:
MS201924-0022
CT.gov Identifier:
NCT05882734
EudraCT Identifier:
202250201085
EU Trial (CTIS) Number:
2022-502010-85-00
Study Contact Information:
(210) 593-5651 or [email protected]
Recruitment Complete

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Study Summary

To establish the efficacy, safety, tolerability, and pharmacokinetics of the ataxia telangiectasia mutated and Rad3-related protein kinase (ATR) inhibitor Tuvusertib in Combination with Cemiplimab in Participants with Non-Squamous Non-Small Cell Lung Cancer (nsqNSCLC) that has Progressed on Prior Anti-PD-(L)1 and Platinum-based Therapies..

Medical Condition
The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.
Non-Small Cell Lung Cancer
Phase
The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
Phase I/II
Sex
Female & Male
Age
18+ years
Study Drug
Drug: Experimental: Dosing Regimen 1 (Phase 1b)
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Drug: Experimental: Dosing Regimen 2 (Phase 1b)
Drug: Experimental: Stratum A (Phase 2a)
Drug: Experimental: Stratum B (Phase 2a)
Drug: Experimental: Stratum C (Phase 2a)
Drug: In the randomised Phase 1b, two dosing regimens, tuvusertib 100 mg once-daily (QD) + cemiplimab 350 mg every three weeks (Q3W) (n=30) or tuvusertib 180 mg QD 2 weeks on/1 week off + cemiplimab 350 mg Q3W (n=30), are being evaluated. Based on a totality of evidence approach, the most favourable regimen will be selected for investigation in Phase 2a, in which patients will be treated in 3 separate strata based on genetic alterations detected in circulating tumor DNA: stratum A (n=40), STK11 or KEAP1; stratum B (n=40), ATM or ARID1A or SMARCA4 or PBRM1; stratum C (n=40), any other/no alterations
Study Status
Indicates the current recruitment status or the expanded access status
Recruitment Complete

Requirements information
Inclusion criteria
  • - Participants who are diagnosed with nsqNSCLC histologically or cytologically confirmed
  • - Participants with Radiologically confirmed/documented disease progression during or
  • after the following systemic therapies (all required):
  • - At most, 1 line of anti-PD-(L)1 therapy for locally advanced or metastatic
  • disease. Rechallenge with the same anti-PD-(L)1 for disease considered sensitive
  • to anti-PD-(L)1 therapy (e.g. after a treatment break) is considered 1 line
  • - Platinum-based therapy for locally advanced or metastatic disease, given in
  • combination or sequentially with anti-PD-(L)1 therapy. Participants who received
  • adjuvant platinum-based therapy meet this criterion if disease progression
  • occurred within 6 months from the last dose that the participant received that
  • therapy. No additional cytotoxic therapies after progression on platinum-based
  • therapy are allowed
  • - Prior best overall response of stable disease or better with anti-PD-(L)1 therapy
  • - Disease progression must have occurred while the participant has been receiving
  • anti-PD-(L)1 therapy or within 16 weeks of the last dose of anti-PD-(L)1 therapy
  • - Participants with Measurable disease per RECIST v1.1
  • - Participants with Eastern Cooperative Oncology Group (ECOG) PS 0 or 1
  • - Adequate hematological, hepatic, and renal function as defined in the protocol.
  • - Phase 2a part only: central liquid biopsy analysis of tumor molecular alterations with
  • an assay with appropriate regulatory status
  • - Other protocol defined inclusion criteria could apply
Exclusion criteria
  • - Participants with tumors harboring actionable epidermal growth factor receptor (EGFR)
  • or anaplastic lymphoma kinase (ALK) genomic aberrations. Participants with tumors with
  • other actionable aberrations are eligible and allowed to have received up to 1 line of
  • available targeted therapy
  • - Participants with history of additional malignancy within 3 years before the date of
  • enrollment. Exceptions are squamous and basal cell carcinomas of the skin and
  • carcinoma in situ of the cervix, or malignancy that in the opinion of the
  • Investigator, with concurrence of the Sponsor's Medical Monitor, is considered cured
  • with minimal risk of recurrence within 3 years
  • - Participants with known brain metastases, unless clinically stable
  • - Participant with history of (noninfectious) pneumonitis that required systemic
  • corticosteroids or current pneumonitis/interstitial lung disease
  • - Other protocol defined exclusion criteria could apply

Clinical Study Information for Healthcare Providers

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Study Locations

Location
Investigator
Status
Condition(s) Treated at Site
Location
START Madrid, Spain (CIOCC)
Madrid, Spain, 28050
Investigator
Gema Garcia Ledo
Status
Terminated/Withdrawn
Condition(s) Treated at Site
Non-Small Cell Lung Cancer