Olaparib and ASTX727 in BRCA1/2- and Homologous Recombination Deficient (HRD)-Mutated Tumors

Part of paid clinical trials in San Francisco, California.

Sponsor
Varun Monga, MBBS
Study ID
NCT06177171
Phase
PHASE1
Status
Recruiting
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Conditions

  • ATM Gene Mutation
  • BRCA Mutation
  • BRCA1 Mutation
  • BRCA2 Mutation
  • Checkpoint Kinase 2 Gene Mutation
  • PALB2 Gene Mutation

Eligibility Criteria

Sex
ALL
Age
18 Years - N/A
Healthy Volunteers
Not accepted

Interventions

  • Olaparib — DRUG
    Given orally
  • ASTX727 — DRUG
    Given Orally

Study Details

This is a single center, phase I/Ib clinical trial evaluating the combination of the poly adenosine diphosphate-ribose polymerase (PARP) inhibitor olaparib with the DNA methyltransferase (DNMT) inhibitor ASTX727, which is an oral formulation of decitabine with cedazuridine (a cytidine deaminase inhibitor that allows for oral administration). The study population consists of adults with advanced/metastatic solid tumor malignancies with germline or somatic mutations in the HRR pathway (i.e., BReast CAncer gene 1 (BRCA1), BReast CAncer gene 2(BRCA2), Partner And Localizer of BRCA2 (PALB2), ATM, and/or Checkpoint kinase 2 (CHEK2) mutations).

Key Dates

Start date
Feb 7, 2024
Status verified
May 2026
Primary completion
Jan 31, 2028
Completion
Jan 31, 2028

Study Design

Enrollment
18 participants (estimated)
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT

Arms

  • Experimental: Phase 1: Olaparib, ASTX727 (D1,D3)-Starting Dose
    Participants enrolled in the starting dose cohort will receive 300 mg Olaparib orally, twice a day (BID) on day 1 and day 14 for each 28-day cycle. Participants will also receive 35/100mg ASTX727 on days 1, and 3 of the 28-day cycle. Participants may continue study treatment indefinitely until disease progression unacceptable toxicity, withdrawal, or study closure; whichever comes first. If no DLTs are reported for the first 3 participants, an additional dose escalation cohort may open at the next dose level.
  • Experimental: Phase 1: Olaparib + ASTX727 (D1,D3,D5)
    If no DLTs are reported in the previous dose level, participants enrolled in this cohort will receive 300 mg olaparib orally, twice a day (BID) on day 1 and day 14 for each 28-day cycle. Participants will also receive 35/100mg ASTX727 on days 1, 3 and 5 of the 28-day cycle. Participants may continue study treatment indefinitely until disease progression unacceptable toxicity, withdrawal, or study closure; whichever comes first.
  • Experimental: Phase 1b: RP2D (Olaparib, ASTX727) - Dose Expansion
    Participants enrolled in this cohort will receive the RP2D based on the safety and efficacy profile determined in the Phase 1 cohorts. Participants will receive the RP2D dose of olaparib orally, twice a day (BID) on day 1 and day 14 for each 28-day cycle. Participants will also receive 35/100mg ASTX727 at the RP2D for the 28-day cycle. Participants may continue study treatment indefinitely until disease progression unacceptable toxicity, withdrawal, or study closure; whichever comes first.

Primary Outcome Measure

Proportion of participants with treatment-emergent Adverse Events (AEs) (Phase 1 Only) [ Time Frame: Up to 2 years ]

Central Contacts

Locations (1)

FacilityCityStateZIPSite coordinators
University of California, San FranciscoSan FranciscoCalifornia94143
Early Phase Cancer Clinical Trials
[email protected]
877-827-3222
[email protected]
Varun Monga, MBBS (PRINCIPAL_INVESTIGATOR)

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By research site
University of California, San Francisco· San Francisco, CA

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