Dosing of Novel PARP Inhibitor for Solid Tumors Begins in Phase 1 Study

The first patient has been dosed in the phase 1/1b study of the novel poly (ADP-ribose) polymerase (PARP) inhibitor RP12146 for the treatment of advanced solid tumors, according to a press release by Rhizen Pharmaceuticals AG.¹

Preclinical studies have found that RP12146 has comparable efficacy and activity to the approved PARP inhibitor olaparib (Lynparza). Additionally, the experimental agent was found to potentially have improved safety.

"PARP inhibitors are a great success story in the DNA damage response area, but they are not without safety concerns that have limited realization of their full potential. Although our novel PARP inhibitor is competing in a crowded space, we expect its superior preclinical safety to translate into the clinic which will differentiate our program and allow us to extend its application beyond the current landscape of approved indications and combinations", said Swaroop Vakkalanka, founder & CEO of Rhizen Pharma, in a press release. "Our PARP program is foundational for our DDR platform efforts and will be the backbone for several novel proprietary combinations that we hope to bring into development going forward."

The phase 1/1b study (NCT05002868) has a target enrollment of 60 participants and an estimated study completion date of August 2023. The primary end points of the study are maximum tolerated dose and the number of patients with treatment-emergent adverse events. Secondary end points include overall response rate, clinical benefit rate, and progression-free survival.²

During the single-arm study, patients will receive RP12146 once daily at a starting dose of 100 mg.

In order to participate in the study, patients must be at least 18 years of age or older at the time of signing informed consent, have a histologically or cytologically confirmed malignant solid tumor and have progressed following at least 1 standard therapy and have no other acceptable standard treatment options, have at least one measurable lesion per RECIST version 1.1 at baseline, an ECOG performance status of 0 to 2, and agree to use contraception. Tumor types include breast, ovarian, fallopian tube, peritoneal cancer, extensive-stage small cell lung cancer, prostate, pancreatic, colorectal, biliary tract, and endometrial cancer.

Patients with HER2-positive breast cancer, who are receiving another anticancer therapy, who have not recovered from acute toxicities of previous therapies with the exception of treatment-related alopecia, prior treatment with a PARP inhibitor, major surgery within 4 weeks of starting study treatment, systemic uncontrolled brain metastasis, pregnancy and lactation, or uncontrolled disease, are not eligible to participate.

_REFERENCES:

_{Rhizen Pharmaceuticals AG announces first patient dosing in a phase I/Ib study of its novel PARP inhibitor (RP12146) in patients with advanced solid tumors. Rhizen Pharmaceuticals AG. November 1, 2021. Accessed November 2, 2021.}

_{Safety, pharmacokinetics and anti-tumor activity of RP12146, a PARP inhibitor, in patients with locally advanced or metastatic solid tumors. ClinicalTrials.gov. Accessed November 2, 2021. https://bit.ly/31f1e}