RP-1664 / Repare Therap - LARVOL DELTA

LIONS (PLK4 Inhibitor in Advanced Solid Tumors) (clinicaltrials.gov) - P1 | N=29 | Active, not recruiting | Sponsor: Repare Therapeutics | Recruiting ➔ Active, not recruiting | N=80 ➔ 29 | Trial completion date: Jan 2027 ➔ Oct 2025 | Trial primary completion date: Jan 2027 ➔ Sep 2025

Enrollment change • Enrollment closed • Trial completion date • Trial primary completion date • Solid Tumor

Discovery of RP-1664: A First-in-Class Orally Bioavailable, Selective PLK4 Inhibitor. (PubMed, J Med Chem) - P1 | "RP-1664 disrupts centriole biogenesis in cancer cells, modulates pharmacodynamic readouts of PLK4 activity in xenograft tumor tissues, and is efficacious in multiple TRIM37-amplified xenograft models. This first-in-class clinical candidate is currently being evaluated in Phase 1 clinical trials (NCT06232408) for treatment of advanced solid tumors."

Journal • Oncology • Solid Tumor • AURKA • PLK1 • PLK4 • TRIM37

Repare Therapeutics Provides Business and Clinical Update and Reports First Quarter 2025 Financial Results (Businesswire) - "First Quarter 2025 and Recent Portfolio Highlights:... (i) RP-3467:...Upcoming expected milestone: Q3 2025: Topline safety, tolerability and early efficacy data from the POLAR trial in monotherapy and in combination with olaparib; (ii) RP-1664:...Upcoming expected milestone: Q4 2025: Initial topline safety, tolerability and early efficacy data from the LIONS trial."

P1 data • Solid Tumor

RP-1664: A potent and selective PLK4 inhibitor causing tumor regressions in TRIM37-high xenograft models of solid tumors (AACR 2025) - P1 | "The highly selective, orally bioavailable PLK4 inhibitor RP-1664 demonstrates overall profound efficacy in pre-clinical in vitro and in vivo xenograft models and activation of the appropriate biomarkers indicating the expected on-target activity. These data suggest that further clinical investigation of RP-1664's anti-tumor activity in breast and other solid tumors is warranted (NCT06232408)."

Preclinical • Breast Cancer • CNS Tumor • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Neuroblastoma • Oncology • Solid Tumor • CDKN1A • HER-2 • PLK4 • TRIM37

A dual mechanism of sensitivity to PLK4 inhibition by RP-1664 in neuroblastoma (AACR 2025) - "HRNB cell models are hypersensitive to centriole amplification induced by low levels of PLK4 inhibition as well as to centriole loss at higher PLK4 inhibitor levels, warranting the investigation of RP-1664 in clinical trials with neuroblastoma patients."

CNS Tumor • Neuroblastoma • Oncology • Solid Tumor • PLK4 • TP53 • TRIM37

Pan-cancer analysis of TRIM37 copy-number and development of fit-for-screening in situ hybridization tools (AACR 2025) - P1 | "This synthetic lethal hypothesis is being tested in a phase I clinical trial evaluating the activity of the PLK4 inhibitor, RP-1664, in advanced solid tumors with TRIM37 CN gains or overexpression (LIONS, NCT06232408)... A considerable population of adult solid tumors are TRIM37-high. Creation of fit-for-screening tools employing in-situ hybridization techniques may provide enhanced sensitivity for identification of patients with TRIM37-high tumors."

Pan tumor • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Lung Adenocarcinoma • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Solid Tumor • HER-2 • PLK4 • TRIM37

The PLK4 inhibitor RP-1664 drives centriole modulation and single agent tumor regressions in preclinical neuroblastoma models (AACR 2025) - "Chromosome 17q gain and TRIM37 overexpression are pathognomonic features of HRNB. The novel PLK4 inhibitor RP-1664 was broadly efficacious across a wide array of highly resistant HRNB preclinical models and support clinical development of this therapy."

Preclinical • CNS Tumor • Neuroblastoma • Oncology • Solid Tumor • ALK • MYCN • PLK4 • TRIM37

Repare Therapeutics Announces Six Abstracts Accepted for Presentation at AACR Annual Meeting 2025 (Businesswire) - "Repare Therapeutics Inc...announced the acceptance of two abstracts for mini-oral presentation and the acceptance of four abstracts for poster presentation at the American Association for Cancer Research (AACR) Annual Meeting, taking place April 25-30, 2025, in Chicago, Illinois."

P1 data • Preclinical • Endometrial Cancer • Gastric Cancer • Neuroblastoma • Ovarian Cancer

Repare Therapeutics Announces Portfolio Re-Prioritization, Partnering Initiatives and Cost Reductions (Businesswire) - "Repare Therapeutics...announced a re-alignment of resources and a re-prioritization of its clinical portfolio to focus on the continued advancement of its Phase 1 clinical programs, RP-1664 (PLK4 inhibitor) and RP-3467 (Polθ ATPase inhibitor). Repare also announced its intention to seek partnering opportunities across its portfolio, including for lunresertib and camonsertib ('Lunre+Camo') prior to any start of pivotal development. The consequent savings of late-stage clinical funding combined with planned cost and headcount reductions are expected to extend Repare’s cash runway into mid-2027."

Commercial • Solid Tumor

Recent Pipeline Progress & Upcoming Milestones of Prioritized Clinical Programs (Businesswire) - "RP-1664: First-in-class, highly selective, oral inhibitor of PLK4...Upcoming Expected Milestones: (i) Q3 2025: Initiation of a Phase 1/2 expansion trial in pediatric neuroblastoma; (ii) Q4 2025: Initial topline safety, tolerability and early efficacy data from the LIONS trial; (iii) Mid-2026: Trial completion, final trial readout for proof-of-concept from the LIONS trial."

New P1/2 trial • P1 data • Trial completion date • Neuroblastoma • Solid Tumor

Repare Therapeutics Announces Strategic Reprioritization to Focus on Broad Clinical Portfolio (Businesswire) - "Repare Therapeutics Inc...today announced the strategic reprioritization of its research and development activities to focus its efforts on the advancement of its portfolio of clinical-stage oncology programs. With multiple upcoming clinical milestones and potential near-term registration-enabling studies, the Company is streamlining its operations to focus on the advancement of its lunresertib, camonsertib, RP-1664 and RP-3467 programs while materially reducing the scale of its preclinical research and discovery activities...'We remain on track to report data from our MYTHIC dose expansion trial evaluating lunresertib in combination with camonsertib in patients with ovarian and endometrial cancers in the fourth quarter of 2024, with the potential to begin a registrational trial in 2025.'"

New trial • P1 data • Endometrial Cancer • Gynecologic Cancers • Oncology • Ovarian Cancer • Solid Tumor

Repare Therapeutics Provides Business and Clinical Update and Reports Second Quarter 2024 Financial Results (Businesswire) - "Second Quarter 2024 and Recent Portfolio Highlights:...(i) RP-1664: Actively enrolling patients into the Phase 1 LIONS trial evaluating RP-1664, a potential first-in-class selective PLK4 inhibitor, in adult and adolescent patients with TRIM37-high advanced solid tumors and other biomarkers. The Company expects to rapidly advance RP-1664 into a Phase 1/2 clinical trial in pediatric patients with high risk, recurrent neuroblastoma, where the patients have a high prevalence of TRIM37-altered tumors, after evaluating the safety profile in the LIONS trial; (ii) RP-3467: Initiation of a Phase 1 dose finding trial of RP-3467, a potential best-in-class Polθ ATPase inhibitor, is expected in the fourth quarter of 2024."

Enrollment status • New P1 trial • New P1/2 trial • Neuroblastoma

ORIC Pharmaceuticals Presents Preclinical Data on Two Programs at the 2024 American Association for Cancer Research (AACR) Annual Meeting (GlobeNewswire) - "ORIC-613 is an orally bioavailable, potent and exquisitely selective small molecule inhibitor of PLK4, which is synthetic lethal in tumor cells with high levels of TRIM37....ORIC-613 has superior kinome selectivity versus comparator compounds CFI-400945 and RP-1664....Preclinical assessment in cancer cell lines revealed synthetic lethality, with ORIC-613 inducing apoptotic tumor cell death specifically in TRIM37-high breast cancer and neuroblastoma cells versus TRIM37-wildtype cells....Oral dosing of ORIC-613 at 150 mg/kg QD resulted in tumor regressions and tumor growth inhibition in TRIM37-high xenograft breast tumors."

Preclinical • Breast Cancer • Oncology • Solid Tumor

LIONS (PLK4 Inhibitor in Advanced Solid Tumors) (clinicaltrials.gov) - P1 | N=80 | Recruiting | Sponsor: Repare Therapeutics | Not yet recruiting ➔ Recruiting

Enrollment open • Metastases • Oncology • Solid Tumor

Repare Therapeutics Doses First Patient in Phase 1 Clinical Trial of RP-1664 (Businesswire) - "Repare Therapeutics Inc...today announced the first patient has been dosed in the Company’s Phase 1 LIONS (PLK4 Inhibitor in Advanced Solid Tumors) clinical trial evaluating RP-1664, a potential first-in-class, highly selective, oral polo-like kinase 4 (PLK4) inhibitor, for the monotherapy treatment of adult and adolescent patients enriched for TRIM37-high solid tumors...'After evaluating safety in the LIONS clinical trial, we expect to move rapidly into a Phase 1/2 clinical trial in high risk, recurrent pediatric neuroblastoma.'....The LIONS clinical trial (NCT06232408) is a first-in-human, multicenter, open-label Phase 1 study to investigate safety, pharmacokinetics, pharmacodynamics and the preliminary efficacy of RP-1664."

Trial status • Oncology • Solid Tumor

LIONS (PLK4 Inhibitor in Advanced Solid Tumors) (clinicaltrials.gov) - P1 | N=80 | Not yet recruiting | Sponsor: Repare Therapeutics

Metastases • New P1 trial • Oncology • Solid Tumor

Repare Therapeutics Provides Corporate Update and Highlights Anticipated Key 2024 Milestones (Businesswire) - "Anticipated Key Milestones in 2024: Initiation of a Phase 1 dose escalation study of RP-1664...in adult and adolescent patients with TRIM37-high solid tumors in the first half of 2024; Initiation of a Phase 1/1b study of lunresertib and Debio 0123, a WEE1 inhibitor, in the first half of 2024; Report initial data from the Phase 1 MINOTAUR study evaluating lunresertib in combination with FOLFIRI for the treatment of advanced solid tumors in the first half of 2024."

New P1 trial • P1 data • Oncology • Solid Tumor

Repare Therapeutics Unveils Two Programs Expected to Enter Clinical Trials in 2024: RP-1664, an Oral PLK4 Inhibitor, and RP-3467, an Oral Polθ Inhibitor (Businesswire) - "Repare Therapeutics Inc...disclosed polo-like kinase 4 (PLK4) as the target of its RP-1664 development program and reported comprehensive preclinical data for both RP-1664 and the Company’s Polθ inhibitor, RP-3467....RP-1664 demonstrated robust and dose-dependent monotherapy activity in multiple TRIM37-high preclinical models across a variety of tumor types, including breast cancer, non-small cell lung cancer (NSCLC) and neuroblastoma. The Company plans to initiate a Phase 1 dose escalation study of RP-1664 in adult and adolescent patients with TRIM37-high solid tumors in the first half of 2024....RP-3467 demonstrates synergy with PARP inhibitor activity, resulting in durable, complete tumor regressions in multiple preclinical models....The Company plans to initiate a Phase 1 dosing finding clinical trial of RP-3467 in the second half of 2024."

New P1 trial • Preclinical • Breast Cancer • Lung Cancer • Neuroblastoma • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Repare Therapeutics Provides Business Update and Reports Third Quarter 2023 Financial Results (Businesswire) - "RP-1664 IND-enabling studies, which began in the first quarter of 2023, are nearing completion and Repare expects to initiate a clinical trial in the first half of 2024. RP-3467 is Repare’s wholly-owned Polθ inhibitor, currently in IND-enabling studies, which began in the second quarter of 2023 and remain ongoing. Repare expects to initiate a clinical trial in the second half of 2024."

New trial • Preclinical • Oncology

Repare Therapeutics Provides Business Update and Reports Second Quarter 2023 Financial Results (Businesswire) - "Repare Therapeutics Inc...today reported financial results for the second quarter ended June 30, 2023...In August 2023, the U.S. Food and Drug Administration (FDA) granted Fast Track designation (FTD) to lunresertib in combination with camonsertib for the treatment of adult patients with CCNE1 amplified, or FBXW7 or PPP2R1A mutated endometrial cancer previously treated with a platinum-containing regimen and immune checkpoint inhibitor when indicated...The Company expects to present further Phase 1 MYTHIC Module 2 combination data with camonsertib at a medical conference in the fourth quarter of this year....RP-1664 IND-enabling studies, which began in the first quarter of 2023, remain ongoing with potential for the program to enter the clinic in early 2024."

Fast track designation • New trial • P1 data • Endometrial Cancer • Gynecologic Cancers • Oncology • Solid Tumor • Uterine Cancer • CCNE1 • FBXW7 • PPP2R1A

Repare Therapeutics Provides Business Update and Reports First Quarter 2023 Financial Results (Businesswire) - "Advancing preclinical programs into clinical development: (i) Repare initiated IND-enabling studies in the first half of this year for a small molecule, now designated RP-1664, against an undisclosed target with potential to enter the clinic in late 2023 or early 2024; (ii) Repare is also pursuing development of an inhibitor of polymerase theta (Polθ) that is expected to enter the clinic in 2024."

New trial • Pipeline update • Oncology