Clinical trial NCT04972110: Study of RP-3500 (Camonsertib) With Niraparib or Olaparib in Advanced Solid Tumors
Official title: Phase 1b/2 Study of ATR InhibiTor RP-3500 and PARP Inhibitor Combinations in Patients With Molecularly Selected Cancers (ATTACC)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Advanced Solid Tumor, Adult
Lead sponsor: Repare Therapeutics
Sponsor class: INDUSTRY
Collaborators: name: Roche Pharma AG
First posted: 2021-07-22
Enrollment: 196
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: Dose Escalation, expansion and Phase 2
Primary purpose: TREATMENT

Brief summary: The primary purpose of this study is to assess the safety and tolerability of niraparib or olaparib in combination with RP-3500 (camonsertib), in patients with eligible advanced solid tumors, determine the maximum tolerated dose (MTD) of RP-3500 (camonsertib) in combination with niraparib or olaparib, examine pharmacokinetics (PK) and assess anti-tumor activity.

Detailed description: This is a first-in-human Phase 1b/2, multi-center, open-label, dose-escalation and expansion study to:

* Evaluate the safety profile and MTD of RP-3500 (camonsertib) when administered orally in combination with niraparib or olaparib to establish the recommended Phase 2 dose and schedule.
* Characterize the PK profile of RP-3500 (camonsertib) in combination with niraparib or olaparib
* Assess anti-tumor activity associated with RP-3500 (camonsertib) in combination with niraparib or olaparib
* Examine biomarker responses and establish a correlation with RP-3500 (camonsertib) treatment in combination with niraparib or olaparib.

After the RP2D and schedule is determined, expansion cohort(s) for RP-3500 (camonsertib) in combination with niraparib or olaparib will be enrolled to study the anti-tumor effect, and further examine the safety, PK, and pharmacodynamic (PD).

Eligibility criteria: Inclusion Criteria:

* Male or female and ≥18 years-of-age at the time of signature of the informed consent
* Confirmed advanced solid tumors resistant or refractory to standard treatment
* Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 or 1.
* Evaluable disease as per RECIST v1.1
* Next generation sequencing (NGS) report obtained in CLIA-certified or equivalent laboratory demonstrating eligible tumor biomarkers.
* Submission of available tumor tissue or willingness to have a biopsy performed if safe and feasible
* Acceptable hematologic and organ function at screening
* Negative pregnancy test for women of childbearing potential at Screening and prior to first study drug.
* Ability to swallow and retain oral medications.

Exclusion Criteria:

* Prior therapy with an ATR or DNA-dependent protein kinase (DNA-PK) inhibitor.
* Chemotherapy, small molecule anticancer or biologic anticancer therapy given within 10 days or 5 half-lives (whichever is longer), prior to first dose of study drug.
* Use of radiotherapy (except for palliative reasons) within 7 days prior to first dose of study drug.
* History or current condition, therapy, or laboratory abnormality that might confound the study results, or interfere with the patient's participation for the full duration of the study treatment.
* No other anticancer therapy is to be permitted while the patient is receiving study treatment.
* Major surgery ≤28 days or minor surgical procedures ≤7 days prior to first study treatment dose.
* Uncontrolled, symptomatic brain metastases.
* Uncontrolled high blood pressure
* History of myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) diagnosis
* Presence of other known active invasive cancers.
* Pregnant or breastfeeding women.
* Psychological, familial, sociological, or geographical conditions that do not permit compliance with the study protocol and/or follow-up procedures outlined in the protocol.

Primary outcomes:
measure: Phase Ib - Safety and Tolerability of niraparib or olaparib in combination with RP-3500 (camonsertib) by assessing the grade and frequency of adverse events and serious adverse events.
timeFrame: Up to 30 days after last administration of study intervention
measure: Primary Phase 1b - Define Maximum Tolerated Dose of RP-3500-03 (camonsertib) in combination with niraparib or olaparib and Recommended Phase 2 Dose and preferred schedule by assessing frequency of Dose Limiting Toxicities observed at each dose level
timeFrame: At the end of cycle 1 (each cycle is 21 or 28 days)
measure: Primary Phase 2 - Assess preliminary anti-tumor activity of RP-3500 (camonsertib) with niraparib or olaparib in patients with eligible advanced solid tumors
timeFrame: While on study therapy, every 6 weeks for first 5 months and then every 9 weeks thereafter
Secondary outcomes:
measure: To assess PK parameters of RP-3500 (camonsertib) in combination with niraparib or olaparib -Cmax
timeFrame: Through Cycle 1 and 2 (each cycle is 21 days)
measure: To assess PK parameters of RP-3500 (camonsertib) in combination with niraparib or olaparib -Tmax
timeFrame: Through Cycle 1 and 2 (each cycle is 21 days)
measure: To assess PK parameters of RP-3500 (camonsertib) in combination with niraparib or olaparib - AUC
timeFrame: Through Cycle 1 and 2 (each cycle is 21 days)
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Participating Site #1018
state: Arizona
city: San Francisco
country: United States
facility: Participating Site #1025
state: California
city: Aurora
country: United States
facility: Participating Site #1028
state: Colorado
city: New Haven
country: United States
facility: Participating Site #1012
state: Connecticut
city: Jacksonville
country: United States
facility: Participating Site #1017
state: Florida
city: Baltimore
country: United States
facility: Participating Site #1009
state: Maryland
city: Ann Arbor
country: United States
facility: Participating Site #1015
state: Michigan
city: Rochester
country: United States
facility: Participating Site # 1016
state: Minnesota
city: New York
country: United States
facility: Participating Site #1026
state: New York
city: New York
country: United States
facility: Participating Site # 1008
state: New York
city: Eugene
country: United States
facility: Participating Site #1029
state: Oregon
city: Houston
country: United States
facility: Participating Site # 1001
state: Texas
city: Salt Lake City
country: United States
facility: Participating Site # 1013
state: Utah
Study officials:
References: