Study of RP-3500, Camonsertib, in Advanced Solid Tumors
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|ClinicalTrials.gov Identifier: NCT04497116|
Recruitment Status : Recruiting
First Posted : August 4, 2020
Last Update Posted : February 9, 2023
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|Condition or disease||Intervention/treatment||Phase|
|Advanced Solid Tumor||Drug: RP-3500 (camonsertib) Drug: Talazoparib Drug: Gemcitabine Injection||Phase 1 Phase 2|
This is a first-in-human, Phase 1/2a, multi-center, open-label, dose-escalation and expansion study to:
- Evaluate the safety profile and MTD of RP-3500 (camonsertib) when administered orally, alone and in combination with talazoparib or gemcitabine, to establish the dose and schedule recommended for the Phase 2
- Characterize the PK profile of RP-3500 (camonsertib) alone or in combination with talazoparib or gemcitabine
- Identify anti-tumor activity associated with RP-3500 (camonsertib) given alone or in combination with talazoparib or gemcitabine
- Examine biomarker responses and establish a correlation with RP-3500 (camonsertib) exposure and clinical outcomes.
The initial cohorts will test RP-3500 (camonsertib) as monotherapy. Additional cohorts will enroll with RP-3500 (camonsertib) in combination with talazoparib or gemcitabine.
After the RP2D and schedule is determined, expansion cohort(s) for RP-3500 (camonsertib) will be enrolled to study the anti-tumor effect, and further examine the safety and PK of RP-3500 (camonsertib) at the RP2D
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||451 participants|
|Intervention Model:||Sequential Assignment|
|Intervention Model Description:||Dose Escalation, expansion and phase 2|
|Masking:||None (Open Label)|
|Official Title:||Phase 1/2a Study of the Safety, Pharmacokinetics, Pharmacodynamics and Preliminary Clinical Activity of RP-3500 Alone or in Combination With Talazoparib or Gemcitabine in Advanced Solid Tumors With ATR Inhibitor Sensitizing Mutations (TRESR Study)|
|Actual Study Start Date :||July 22, 2020|
|Estimated Primary Completion Date :||January 30, 2024|
|Estimated Study Completion Date :||March 30, 2024|
Experimental: RP-3500 (camonsertib) alone
Multiple doses of RP-3500 (camonsertib) for oral administration alone
Drug: RP-3500 (camonsertib)
Oral ATR inhibitor
Experimental: Expansion cohorts with RP-3500 (camonsertib)
Expansion cohorts with RP-3500 (camonsertib)
Drug: RP-3500 (camonsertib)
Oral ATR inhibitor
Experimental: RP-3500 (camonsertib) with Talazoparib or Gemcitabine
Multiple doses of RP-3500 (camonsertib) for oral administration in combination with talazoparib or gemcitabine
Drug: RP-3500 (camonsertib)
Oral ATR inhibitor
Oral PARP inhibitor
Drug: Gemcitabine Injection
- To define the Maximum Tolerated Dose (MTD) which will then be used to inform and determine the Recommended Phase 2 Dose (RP2D) and schedule alone or in combination with talazoparib or gemcitabine [ Time Frame: Up to 90 days after last administration of study intervention ]
- Frequency of Dose limiting Toxicities (DLTs) [ Time Frame: At the end of cycle 1 (each cycle is 21 days or 28 days) ]
- Safety and tolerability [ Time Frame: Up to 90 days after last administration of study intervention ]Grade and frequency of adverse events and serious adverse events
- Assess preliminary anti-tumor activity with Overall Response Rate in patients with eligible advanced solid tumors by CT/MRI Response evaluation criteria in solid tumors (RECIST 1.1) or confirmed response in CA-125 or PSA per GCIG or PSWG criteria. [ Time Frame: About 1 year ]Overall response rate
- Assess preliminary anti-tumor activity with Overall Response Rate in patients with eligible advanced solid tumors by CT/MRI Response evaluation criteria in solid tumors (RECIST 1.1) [ Time Frame: About 1 year ]Objective response rate (ORR)
- Assess CR+PR+SD (≥ 4 months) based on RECIST v1.1, confirmed CA-125 response by GCIG criteria, or PSA response based on PCWG3 [ Time Frame: About 1 year ]Clinical Benefit Rate
- Assess preliminary anti-tumor activity with Duration of Response (DOR) in patients with eligible advanced solid tumors by CT/MRI Response evaluation criteria in solid tumors (RECIST 1.1). [ Time Frame: About 1 year ]Duration of response (DOR)
- Characterize the pharmacokinetic profile of RP-3500 (camonsertib) [ Time Frame: Through Study Day 152 ]Area-under-the-curve (AUC 0-inf)
- Peak plasma concentration [ Time Frame: Through Study Day 152 ]Cmax
- To assess PK parameters of RP-3500 (camonsertib) monotherapy in fasted and fed states [ Time Frame: Through Study Day 152 ]Comparison of geometric mean ratios (GMR)
- Pharmacodynamic biomarkers of DNA damage (e.g. gH2AX) will be measured by immunohistochemistry and the percentage of positive cells will be compared between the pre and post treatment biopsies to evaluate target engagement [ Time Frame: Through Study Day -28 to Day 66 (each cycle is 21 days) ]Tumor tissue samples will be collected pre and post dosing
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
|Ages Eligible for Study:||18 Years and older (Adult, Older Adult)|
|Sexes Eligible for Study:||All|
|Accepts Healthy Volunteers:||No|
- Written informed consent, according to local guidelines, signed and dated by the patient or legal guardian prior to the performance of any study-specific procedures, sampling, or analyses.
- Male or female and ≥ 18 years-of-age at the time of signature of the consent.
- Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 or 1.
- Histologically confirmed solid tumors resistant or refractory to standard treatment and/or patients who are intolerant to standard therapy.
- Measurable disease as per RECIST v1.1
- Existing biomarker profile (tumor tissue or plasma) reported from a local test obtained in a certified lab per institutional guidelines:
- Available tumor tissue
- Ability to comply with the protocol and study procedures detailed in the Schedule of Assessments.
- Ability to swallow and retain oral medications.
- Acceptable organ function at screening
- Acceptable blood counts at screening
- Negative pregnancy test (serum or urine) for females of childbearing potential at Screening and prior to first study drug.
- Resolution of all toxicities of prior treatment or surgery.
- Male patients with female partners of childbearing potential and females of childbearing potential must follow a contraception method (oral contraceptives allowed) during their participation in the study and for at least 6 months following last dose of study drug. Male patients must also refrain from donating sperm during their participation in the study and for 6 months following last dose of study drug.
- Chemotherapy, small molecule anticancer or biologic anticancer therapy given within 14 days prior to first dose of study drug.
- History or current condition (such as transfusion dependent anemia or thrombocytopenia), 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.
- Prior therapy with an ATR or DNA-dependent protein kinase (DNA-PK) inhibitor.
- Known hypersensitivity to any of the ingredients of RP-3500 (camonsertib).
- Life-threatening illness, medical condition, active uncontrolled infection, or organ system dysfunction or other reasons which, in the investigator's opinion, could compromise the patient's safety.
- Uncontrolled, symptomatic brain metastases.
- Uncontrolled high blood pressure
- Patients with active, uncontrolled bacterial, fungal, or viral infection, including hepatitis B virus (HBV), hepatitis C virus (HCV), known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS) related illness.
- Moderate or severe hepatic impairment (ie, Child-Pugh class B or C).
- History or presence of an abnormal ECG that is clinically significant in the investigator's opinion.
- History of ventricular dysrhythmias or risk factors such as structural heart disease, coronary heart disease (clinically significant electrolyte abnormalities or family history of sudden unexplained death or long QT syndrome
- Current treatment with medications that are well-known to prolong the QT interval
- History of myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) diagnosis
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04497116
|Contact: Gabriela Gomez, MD, MBAemail@example.com|
|United States, Illinois|
|Participating Site 1014||Recruiting|
|Chicago, Illinois, United States, 60611|
|United States, Massachusetts|
|Participating Site 1006||Recruiting|
|Boston, Massachusetts, United States, 02114|
|Participating Site 1002||Recruiting|
|Boston, Massachusetts, United States, 02215|
|United States, New York|
|Participating Site 1004||Recruiting|
|New York, New York, United States, 10065|
|United States, North Carolina|
|Participating Site 1005||Recruiting|
|Durham, North Carolina, United States, 27710|
|United States, Rhode Island|
|Participating Site 1007||Recruiting|
|Providence, Rhode Island, United States, 02903|
|United States, Tennessee|
|Participating Site 1003||Recruiting|
|Nashville, Tennessee, United States, 37203|
|United States, Texas|
|Participating Site 1001||Recruiting|
|Houston, Texas, United States, 77030|
|Participating Site 2001||Recruiting|
|Toronto, Ontario, Canada, M5G 2M9|
|Participating Site 4001||Recruiting|
|Copenhagen, DK, Denmark, 2100 Ø|
|Participating Site 3003||Recruiting|
|London, United Kingdom, W1G 6AD|
|Participating Site 3001||Recruiting|
|Manchester, United Kingdom, M20 4BX|
|Participating Site 3002||Recruiting|
|Newcastle Upon Tyne, United Kingdom, NE7 7DN|
|Principal Investigator:||Timothy A Yap, MBBS PhD FRCP||M.D. Anderson Cancer Center|
|Responsible Party:||Repare Therapeutics|
|Other Study ID Numbers:||
2020-000301-87 ( EudraCT Number )
|First Posted:||August 4, 2020 Key Record Dates|
|Last Update Posted:||February 9, 2023|
|Last Verified:||February 2023|
|Individual Participant Data (IPD) Sharing Statement:|
|Plan to Share IPD:||No|
|Studies a U.S. FDA-regulated Drug Product:||Yes|
|Studies a U.S. FDA-regulated Device Product:||No|
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