Study of RP-3500 (Camonsertib) With Niraparib or Olaparib in Advanced Solid Tumors

Advanced Solid Tumor, Adult Clinical Trial

— ATTACC  

Official title:

Phase 1b/2 Study of ATR InhibiTor RP-3500 and PARP Inhibitor Combinations in Patients With Molecularly Selected Cancers (ATTACC)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04972110
• Other study ID #: RP-3500-03
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: July 21, 2021
• Est. completion date: December 2025

Study information

• Verified date: November 2023
• Source: Repare Therapeutics
• Contact: Gabriela Gomez, MD, MBA
• Phone: 1 (857) 340-5402
• Email: clininfo[@]reparerx.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 196
• Est. completion date: December 2025
• Est. primary completion date: March 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Advanced Solid Tumor, Adult

Intervention

Drug:
• RP-3500 (camonsertib)
RP-3500 (camonsertib, ATR inhibitor) in combination with niraparib or olaparib (PARP inhibitors)

Locations

Country	Name	City	State
United States	Participating Site #1015	Ann Arbor	Michigan
United States	Participating Site #1028	Aurora	Colorado
United States	Participating Site #1009	Baltimore	Maryland
United States	Participating Site #1029	Eugene	Oregon
United States	Participating Site # 1001	Houston	Texas
United States	Participating Site #1017	Jacksonville	Florida
United States	Participating Site #1012	New Haven	Connecticut
United States	Participating Site # 1008	New York	New York
United States	Participating Site #1026	New York	New York
United States	Participating Site #1018	Phoenix	Arizona
United States	Participating Site # 1016	Rochester	Minnesota
United States	Participating Site # 1013	Salt Lake City	Utah
United States	Participating Site #1025	San Francisco	California

Sponsors (2)

Lead Sponsor	Collaborator
Repare Therapeutics	Roche Pharma AG

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	To determine the safety and tolerability of niraparib or olaparib in combination with RP-3500 (camonsertib) in patients with advanced solid tumors by assessing the grade and frequency of adverse events and serious adverse events	Up to 30 days after last administration of study intervention
Primary	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	To define the Maximum Tolerated Dose of RP-3500-03 (camonsertib) in combination with niraparib or olaparib and determine Recommended Phase 2 Dose and preferred schedule by assessing the frequency of Dose Limiting Toxicities observed at each dose level	At the end of cycle 1 (each cycle is 21 or 28 days)
Primary	Primary Phase 2 - Assess preliminary anti-tumor activity of RP-3500 (camonsertib) with niraparib or olaparib in patients with eligible advanced solid tumors	To preliminarily assess the antitumor activity of RP-3500 (camonsertib) with niraparib or olaparib in patients with eligible advanced solid tumors by Response evaluation criteria (RECIST 1.1 CA-125 per GCIG, and PSA per PCWG3)	While on study therapy, every 6 weeks for first 5 months and then every 9 weeks thereafter
Secondary	To assess PK parameters of RP-3500 (camonsertib) in combination with niraparib or olaparib -Cmax	To assess plasma concentrations of RP-3500 (camonsertib) and niraparib or olaparib with calculations of maximum observed plasma concentration (Cmax)	Through Cycle 1 and 2 (each cycle is 21 days)
Secondary	To assess PK parameters of RP-3500 (camonsertib) in combination with niraparib or olaparib -Tmax	To assess plasma concentrations of RP-3500 (camonsertib) and niraparib or olaparib with calculations of time to maximum observed plasma concentration (Tmax)	Through Cycle 1 and 2 (each cycle is 21 days)
Secondary	To assess PK parameters of RP-3500 (camonsertib) in combination with niraparib or olaparib - AUC	To assess plasma concentrations of RP-3500 (camonsertib) and niraparib or olaparib with calculations of area under the plasma concentration-time curve 0-6 hours post dose (AUC0-6).	Through Cycle 1 and 2 (each cycle is 21 days)