Safety, Pharmacokinetics and Anti-tumor Activity of RP12146, a PARP Inhibitor, in Patients With Locally Advanced or Metastatic Solid Tumors

Study Overview
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Brief Summary
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An open-label, two-part Phase I/Ib study of RP12146 in adult patients with locally advanced or metastatic solid tumors. The first part (Part 1) is a Phase I dose-escalation, 3+3 design, open-label, MTD determination study and will enroll patients who have tumors known to harbour DNA repair deficiencies. The second part (Part 2) is a Phase Ib, dose-expansion at the MTD (or optimal dose) and will enroll patients with a confirmed deleterious HRR mutation in their tumor as identified by a central genomics testing laboratory.

Official Title
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A Multi-center, Open-label, Phase I/Ib Study to Assess the Safety, Pharmacokinetics and Anti-tumor Activity of RP12146, a Poly (ADP-ribose) Polymerase (PARP) Inhibitor, in Patients With Locally Advanced or Metastatic Solid Tumors

Conditions
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Solid Tumor, Extensive-stage Small-cell Lung Cancer, Locally Advanced Breast Cancer, Metastatic Breast Cancer, Platinum-sensitive Ovarian Cancer, Platinum-Sensitive Fallopian Tube Carcinoma, Platinum-Sensitive Peritoneal Cancer

Intervention / Treatment
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* Drug: RP12146


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria. Provision of full informed consent prior to any study-specific procedures. Patients must be ≥18 years of age, at the time of signing informed consent. Dose escalation phase, patients with histologically and/or cytologically confirmed malignant solid tumor whose disease has progressed following at least one standard therapy and who have no other acceptable standard treatment options. Tumor types will include breast, ovarian, fallopian tube, or peritoneal cancer, extensive-stage small cell lung cancer (ES-SCLC), prostate, pancreatic, colorectal gastric, biliary tract, and endometrial cancer. Dose-expansion phase patients with histologically and/or cytologically confirmed malignant solid tumor (breast, ovarian, fallopian tube, or peritoneal cancer, extensive-stage small cell lung cancer (ES-SCLC), with one of the documented deleterious mutations of specified HRR genes and whose disease has progressed following at least one standard therapy. Patients with at least one measurable lesion per RECIST version 1.1 at baseline that can be accurately assessed by CT-scan or MRI and is suitable for repeated assessment at follow up-visits. ECOG performance status 0 to 2. Use of contraception measures Exclusion Criteria: Patients with HER2 positive breast cancer Patients receiving anticancer therapy Patient who has not recovered from acute toxicities of previous therapy except treatment-related alopecia. Prior treatment with a PARP inhibitor Major surgery within 4 weeks of starting study treatment or any patient who has not recovered from the effects of major surgery. Patient with symptomatic uncontrolled brain metastasis. Pregnancy and lactation Patients with uncontrolled disease

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: RP12146<br>RP12146 will be administered orally daily (QD or BID) | Drug: RP12146<br>* starting dose of 100 mg QD<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum tolerated dose (MTD) of RP12146 in patients with locally advanced or metastatic solid tumors | The MTD was defined as the highest dose level at which no more than 1 in 6 participants experienced a dose-limiting toxicity (DLT) during the first 28-day cycle of treatment | 28 days | 
| Number of Participants With Treatment-emergent Adverse Events as Assessed by CTCAE Criteria v5.0 | Summary of Treatment-Emergent Adverse Events-(Causality All). Patients will be monitored for adverse events and both related and as well as non-related adverse events will be captured during the study. All adverse events (irrespective of causality) will be reported. | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tmax | Pharmacokinetics: Time to Reach Maximum Concentration (Tmax) of RP12146 | Day 1 to Day 28 | 
| Cmax | Pharmacokinetics: Maximum Concentration (Cmax) of RP12146 | Day 1 to Day 28 | 
| AUC | Pharmacokinetics: Area Under the Concentration Curve (AUC) of RP12146 | Day 1 to Day 28 | 
| Overall response rate (ORR) | Sum of the percentages of Complete Response and Partial Response | 2 years | 
| Clinical benefit rate (CBR) | Sum of the percentages of Complete response, partial response and stable disease | 2 years | 
| Progression free survival (PFS) | It is defined as time from the first dose of study treatment to documented disease progression | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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PARP