Safety, Pharmacokinetics and Anti-tumor Activity of RP12146, in Patients With Solid Tumors

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Solid Tumor; Metastatic Breast Cancer; Locally Advanced Breast Cancer; Extensive-stage Small-cell Lung Cancer; Platinum-Sensitive Fallopian Tube Carcinoma; Platinum-sensitive Ovarian Cancer; Platinum-Sensitive Peritoneal Cancer
• Intervention / Treatment: Drug: RP12146

• Study Type: Interventional
• Enrollment (Actual): 23
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Prajak I Barde, MD; Phone Number: +41325800175; Email: pjb@rhizen.com

Study Locations

• Czechia
  • Hořovice, Czechia, 268 31
    • Multiscan s.r.o.
  • Olomouc, Czechia, 779 00
    • FN Olomouc, Oncology clinic,
• Poland
  • Poznań, Poland
    • Pratia Poznan Medical Center
  • Toruń, Poland
    • Clinical Trials Site Nasz Lekarz
  • Warszawa, Poland
    • Maria Skłodowska-Curie Memorial National Oncology Institute
  • Łódź, Poland, 93-338
    • Klinika Onkologii ICZMP

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria.

1. Provision of full informed consent prior to any study-specific procedures.
2. Patients must be ≥18 years of age, at the time of signing informed consent.
3. 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.
4. 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.
5. 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.
6. ECOG performance status 0 to 2.
7. Use of contraception measures

Exclusion Criteria:

1. Patients with HER2 positive breast cancer
2. Patients receiving anticancer therapy
3. Patient who has not recovered from acute toxicities of previous therapy except treatment-related alopecia.
4. Prior treatment with a PARP inhibitor
5. Major surgery within 4 weeks of starting study treatment or any patient who has not recovered from the effects of major surgery.
6. Patient with symptomatic uncontrolled brain metastasis.
7. Pregnancy and lactation
8. Patients with uncontrolled disease

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: RP12146; RP12146 will be administered orally daily (QD or BID)	Drug: RP12146; starting dose of 100 mg QD

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Rhizen Pharmaceuticals SA

Study record dates

Study Major Dates

• Study Start (Actual): October 5, 2021
• Primary Completion (Estimated): April 30, 2024
• Study Completion (Estimated): April 30, 2024

Study Registration Dates

• First Submitted: August 5, 2021
• First Submitted That Met QC Criteria: August 5, 2021
• First Posted (Actual): August 12, 2021

Study Record Updates

• Last Update Posted (Actual): April 3, 2024
• Last Update Submitted That Met QC Criteria: April 2, 2024
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Keywords: PARP
• Additional Relevant MeSH Terms: Skin Diseases; Respiratory Tract Diseases; Immune System Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Breast Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Hypersensitivity; Breast Neoplasms; Small Cell Lung Carcinoma
• Other Study ID Numbers: RP12146-2101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No