ATTACC: Study of RP-3500 With Niraparib or Olaparib in Advanced Solid Tumors
Study Details
Study Description
Brief Summary
The primary purpose of this study is to assess the safety and tolerability of Niraparib or Olaparib in combination with RP-3500, in patients with eligible advanced solid tumors, determine the maximum tolerated dose (MTD) of RP-3500 in combination with Niraparib or Olaparib, examine pharmacokinetics (PK) and assess anti-tumor activity.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1/Phase 2 |
Detailed Description
This is a first-in-human Phase 1b/2, multi-center, open-label, dose-escalation and expansion study to:
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Evaluate the safety profile and MTD of RP-3500 when administered orally in combination with Niraparib or Olaparib to establish the recommended Phase 2 dose and schedule.
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Characterize the PK profile of RP-3500 in combination with Niraparib or Olaparib
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Assess anti-tumor activity associated with RP-3500 in combination with Niraparib or Olaparib
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Examine biomarker responses and establish a correlation with RP-3500 treatment in combination with Niraparib or Olaparib.
After the RP2D and schedule is determined, expansion cohort(s) for RP-3500 in combination with Niraparib or Olaparib will be enrolled to study the anti-tumor effect, and further examine the safety, PK, and pharmacodynamic (PD).
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Phase Ib Dose Escalation Multiple dose levels of RP-3500 for oral administration in combination with Niraparib and/or Multiple dose levels of RP-3500 for oral administration in combination with Olaparib |
Drug: RP-3500
RP-3500 (ATR inhibitor) in combination with Niraparib or Olaparib (PARP inhibitors)
Other Names:
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| Experimental: Phase 2 Expansion Cohorts Expansion cohort with RP-3500 + Niraparib and/or Expansion cohort RP-3500 + Olaparib |
Drug: RP-3500
RP-3500 (ATR inhibitor) in combination with Niraparib or Olaparib (PARP inhibitors)
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Phase Ib - Safety and Tolerability Tolerability of niraparib or olaparib in combination with RP-3500 by assessing the grade and frequency of adverse events and serious adverse events. [Up to 30 days after last administration of study intervention]
To determine the safety and tolerability of niraparib or olaparib in combination with RP-3500 in patients with advanced solid tumors by assessing the grade and frequency of adverse events and serious adverse events
- Primary Phase 1b - Define Maximum Tolerated Dose (MTD) of RP-3500-03 in combination with niraparib or olaparib and Recommended Phase 2 dose (RP2D) 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 days)]
To define the MTD of RP-3500-03 in combination with niraparib or olaparib and determine a recommended Phase 2 dose (RP2D) and preferred schedule by assessing the frequency of Dose limiting Toxicities (DLTs) observed at each dose level
- Primary Phase 2 - Assess preliminary anti-tumor activity of RP-3500 with niraparib or olaparib in patients with eligible advanced solid tumors by CT/MRI Response evaluation criteria (RECIST 1.1) [While on study therapy, every 6 weeks for first 5 months and then every 9 weeks thereafter]
To preliminarily assess the antitumor activity of RP-3500 with niraparib or olaparib in patients with eligible advanced solid tumors by CT/MRI Response evaluation criteria (RECIST 1.1)
Secondary Outcome Measures
- To assess plasma concentrations of RP-3500 and niraparib or olaparib with calculations of maximum observed plasma concentration (Cmax). [Through Cycle 1 and 2 (each cycle is 21 days)]
To assess PK parameters of RP-3500 in combination with niraparib or olaparib
- To assess plasma concentrations of RP-3500 and niraparib or olaparib with calculations of time to maximum observed plasma concentration (Tmax) [Through Cycle 1 and 2 (each cycle is 21 days)]
To assess plasma concentrations of RP-3500 and niraparib or olaparib with calculations of time to maximum observed plasma concentration (Tmax)
- To assess plasma concentrations of RP-3500 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)]
To assess plasma concentrations of RP-3500 and niraparib or olaparib with calculations of area under the plasma concentration-time curve 0-6 hours post dose (AUC0-6).
Eligibility Criteria
Criteria
Inclusion Criteria:
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Male or female and ≥18 years-of-age at the time of signature of the informed consent
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Confirmed advanced solid tumors resistant or refractory to standard treatment
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Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 or 1.
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Measurable disease as per RECIST v1.1
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Next generation sequencing (NGS) report obtained in CLIA-certified or equivalent laboratory demonstrating eligible tumor biomarkers.
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Submission of available tumor tissue or willingness to have a biopsy performed if safe and feasible
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Acceptable hematologic and organ function at screening
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Negative pregnancy test for women of childbearing potential at Screening and prior to first study drug.
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Ability to swallow and retain oral medications.
Exclusion Criteria:
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Prior therapy with an ATR or DNA-dependent protein kinase (DNA-PK) inhibitor.
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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.
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Use of radiotherapy (except for palliative reasons) within 7 days prior to first dose of study drug.
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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.
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No other anticancer therapy is to be permitted while the patient is receiving study treatment.
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Major surgery ≤28 days or minor surgical procedures ≤7 days prior to first study treatment dose.
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Uncontrolled, symptomatic brain metastases.
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Uncontrolled high blood pressure
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History of myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) diagnosis
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Presence of other known active invasive cancers.
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Pregnant or breastfeeding women.
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Psychological, familial, sociological, or geographical conditions that do not permit compliance with the study protocol and/or follow-up procedures outlined in the protocol.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Participating Site #1012 | New Haven | Connecticut | United States | 06511 |
| 2 | Participating Site #1009 | Baltimore | Maryland | United States | 21205 |
| 3 | Participating Site #1015 | Ann Arbor | Michigan | United States | 48109 |
| 4 | Participating Site # 1016 | Rochester | Minnesota | United States | 55905 |
| 5 | Participating Site # 1008 | New York | New York | United States | 10032 |
| 6 | Participating Site # 1001 | Houston | Texas | United States | 77030 |
| 7 | Participating Site # 1013 | Salt Lake City | Utah | United States | 84112 |
Sponsors and Collaborators
- Repare Therapeutics
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- RP-3500-03