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

• ClinicalTrials.gov Identifier: NCT05002868
• Recruitment Status: Active, not recruiting
• First Posted: August 12, 2021
• Last Update Posted: May 31, 2023
• Sponsor: Rhizen Pharmaceuticals SA
• Information provided by (Responsible Party): Rhizen Pharmaceuticals SA

Tracking Information

• First Submitted Date: August 5, 2021
• First Posted Date: August 12, 2021
• Last Update Posted Date: May 31, 2023
• Actual Study Start Date: October 5, 2021
• Estimated Primary Completion Date: December 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: August 5, 2021)

• Maximum tolerated dose (MTD) of RP12146 in patients with locally advanced or metastatic solid tumors [ Time Frame: 28 days ]
  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
• Number of Participants With Treatment-emergent Adverse Events as Assessed by CTCAE Criteria v5.0 [ Time Frame: 2 years ]
  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.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: August 5, 2021)

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

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Safety, Pharmacokinetics and Anti-tumor Activity of RP12146, a PARP Inhibitor, in Patients With Locally Advanced or Metastatic Solid Tumors
• Official Title: 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
• Brief Summary: 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• 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

Drug: RP12146

starting dose of 100 mg QD

Study Arms

Experimental: RP12146

RP12146 will be administered orally daily (QD or BID)

Intervention: Drug: RP12146

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: May 30, 2023): 23
• Original Estimated Enrollment (submitted: August 5, 2021): 60
• Estimated Study Completion Date: February 2024
• Estimated Primary Completion Date: December 2023 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Czechia, Poland

Administrative Information

• NCT Number: NCT05002868
• Other Study ID Numbers: RP12146-2101
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• 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

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Rhizen Pharmaceuticals SA
• Original Responsible Party: Same as current
• Current Study Sponsor: Rhizen Pharmaceuticals SA
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Rhizen Pharmaceuticals SA
• Verification Date: May 2023