- |||||||||| lunresertib (RP-6306) / Repare Therap
Trial completion date, Trial primary completion date: RP-6306 in Patients With Advanced Cancer (clinicaltrials.gov) - Jan 8, 2025 P2, N=78, Recruiting, Trial completion date: Jun 2025 --> May 2026 | Trial primary completion date: Dec 2024 --> Dec 2025
- |||||||||| lunresertib (RP-6306) / Repare Therap
Journal: Low Molecular Weight Cyclin E Confers a Vulnerability to PKMYT1 Inhibition in Triple-Negative Breast Cancer. (Pubmed Central) - Nov 16, 2024 Inhibiting PKMYT1 with the selective inhibitor RP-6306 (lunresertib) elicited LMW-E-dependent antitumor effects, accelerating premature mitotic entry, inhibiting replication fork restart, and enhancing DNA damage, chromosomal breakage, apoptosis, and replication stress...Lastly, transcriptomic and immune profiling demonstrated that RP-6306 treatment induced interferon responses and T-cell infiltration in the LMW-E-high tumor microenvironment, enhancing the antitumor immune response. These findings highlight the LMW-E/PKMYT1/CDK1 regulatory axis as a promising therapeutic target in TNBC, providing the rationale for further clinical development of PKMYT1 inhibitors in this aggressive breast cancer subtype.
- |||||||||| lunresertib (RP-6306) / Repare Therap
PKMYT1 Kinase Is an Actionable Synthetically Lethal Target for Del17p Myeloma (Pacific Ballroom Salons 24-26 (Marriott Marquis San Diego Marina)) - Nov 6, 2024 - Abstract #ASH2024ASH_2108; We next evaluated RP-6306 (lunresertib) a selective inhibitor of PKMYT1 catalytic activity for its potential preferential activity against del17p MM cells...We also assessed whether DNA-damaging agents (melphalan, bendamustine) rendered cells sensitive to PKMYT1 inhibition or synergized with it...In conclusion, PKMYT1 is an actionable target for MM cells harboring del17p. PKMYT1 inhibition with lunresertib specifically induced DNA damage, mitotic catastrophe, and subsequent cell death in MM cell lines with del17p or TP53 impairment, representing a potential tailored therapeutic option for this high-risk group of MM patients.
- |||||||||| lunresertib (RP-6306) / Repare Therap
Enrollment closed, Enrollment change, Combination therapy, Metastases: MINOTAUR: Study of RP-6306 With FOLFIRI in Advanced Solid Tumors (clinicaltrials.gov) - Mar 12, 2024 P1, N=36, Active, not recruiting, Not yet recruiting --> Active, not recruiting | Initiation date: Dec 2023 --> Mar 2024 Recruiting --> Active, not recruiting | N=104 --> 36
- |||||||||| camonsertib (RP-3500) / Roche
Journal: Discovery of the Potent and Selective ATR Inhibitor Camonsertib (RP-3500). (Pubmed Central) - Feb 1, 2024 P1, P1/2, Camonsertib is currently undergoing clinical evaluation both as a single agent and in combination with talazoparib, olaparib, niraparib, lunresertib, or gemcitabine (NCT04497116, NCT04972110, NCT04855656). A preliminary recommended phase 2 dose for monotherapy was identified as 160 mg QD given 3 days/week.
- |||||||||| lunresertib (RP-6306) / Repare Therap
Enrollment closed, Trial primary completion date, Combination therapy, Metastases: MAGNETIC: Study of RP-6306 With Gemcitabine in Advanced Solid Tumors (clinicaltrials.gov) - Jan 28, 2024 P1, N=104, Active, not recruiting, Trial completion date: Dec 2024 --> Dec 2026 | Trial primary completion date: Oct 2023 --> Jun 2026 Recruiting --> Active, not recruiting | Trial primary completion date: Oct 2023 --> Dec 2024
- |||||||||| lunresertib (RP-6306) / Repare Therap
Trial completion date, Trial primary completion date: RP-6306 in Patients With Advanced Cancer (clinicaltrials.gov) - Dec 15, 2023 P2, N=78, Recruiting,
- |||||||||| lunresertib (RP-6306) / Repare Therap
Trial completion date, Trial primary completion date, Combination therapy, Metastases: MINOTAUR: Study of RP-6306 With FOLFIRI in Advanced Solid Tumors (clinicaltrials.gov) - Aug 14, 2023 P1, N=104, Recruiting, Co-expression of LMW-E and CDK1-pT14 in TNBC can be used to stratify patients whose tumors are likely to respond to RP-6306, emphasizing its therapeutic significance. Trial completion date: Dec 2024 --> Nov 2026 | Trial primary completion date: Jun 2023 --> Jul 2026
- |||||||||| lunresertib (RP-6306) / Repare Therap
Trial completion date, Trial primary completion date, Combination therapy, Metastases: MAGNETIC: Study of RP-6306 With Gemcitabine in Advanced Solid Tumors (clinicaltrials.gov) - Aug 1, 2023 P1, N=104, Recruiting, Initiation date: Jan 2023 --> Jun 2023 Trial completion date: Dec 2023 --> Apr 2025 | Trial primary completion date: Nov 2022 --> Oct 2023
- |||||||||| lunresertib (RP-6306) / Repare Therap
Enrollment open, Trial initiation date: RP-6306 in Patients With Advanced Cancer (clinicaltrials.gov) - May 31, 2023 P2, N=78, Recruiting, Trial completion date: Dec 2023 --> Apr 2025 | Trial primary completion date: Nov 2022 --> Oct 2023 Not yet recruiting --> Recruiting | Initiation date: Jan 2023 --> Apr 2023
- |||||||||| lunresertib (RP-6306) / Repare Therap, camonsertib (RP-3500) / Repare Therap, Zejula (niraparib) / GSK, J&J
Enrollment open, Liquid biopsy: Liquid-biopsy Informed Platform Trial to Evaluate CDK4/6-inhibitor Resistant ER+/HER2- Metastatic Breast Cancer (clinicaltrials.gov) - Feb 8, 2023 P2, N=484, Recruiting, Mechanistically, LMW-E overexpressing TNBC cells activate CDK1 (in vitro and in vivo) to accelerate premature mitotic entry, leading to DNA damage and apoptosis. Not yet recruiting --> Recruiting
- |||||||||| RP 6306 / Repare Therap
Journal: Discovery of an Orally Bioavailable and Selective PKMYT1 Inhibitor, RP-6306. (Pubmed Central) - Aug 14, 2022 RP-6306 inhibits CCNE1-amplified tumor cell growth in several preclinical xenograft models. The first-in-class clinical candidate RP-6306 is currently being evaluated in Phase 1 clinical trials for treatment of various solid tumors.
- |||||||||| lunresertib (RP-6306) / Repare Therap, camonsertib (RP-3500) / Repare Therap
Enrollment change, Trial completion date, Trial primary completion date, Combination therapy, Metastases: MYTHIC: Study of RP-6306 Alone or in Combination With RP-3500 or Debio 0123 in Patients With Advanced Solid Tumors (clinicaltrials.gov) - May 2, 2022 P1, N=120, Recruiting, The first-in-class clinical candidate RP-6306 is currently being evaluated in Phase 1 clinical trials for treatment of various solid tumors. N=60 --> 120 | Trial completion date: Jun 2023 --> Apr 2024 | Trial primary completion date: Apr 2023 --> Oct 2023
- |||||||||| RP 6306 / Repare Therap
Journal, Synthetic lethality: CCNE1 amplification is synthetic lethal with PKMYT1 kinase inhibition. (Pubmed Central) - Apr 30, 2022 CCNE1 overexpression disrupts CDK1 homeostasis at least in part through an early activation of the MMB-FOXM1 mitotic transcriptional program. We conclude that PKMYT1 inhibition is a promising therapeutic strategy for CCNE1-amplified cancers.
- |||||||||| lunresertib (RP-6306) / Repare Therap
Trial completion date, Trial initiation date, Trial primary completion date, Combination therapy, Metastases: MINOTAUR: Study of RP-6306 With FOLFIRI in Advanced Solid Tumors (clinicaltrials.gov) - Apr 14, 2022 P1, N=104, Recruiting, We conclude that PKMYT1 inhibition is a promising therapeutic strategy for CCNE1-amplified cancers. Trial completion date: Dec 2023 --> Dec 2024 | Initiation date: Feb 2022 --> Jun 2022 | Trial primary completion date: Nov 2022 --> Jun 2023
- |||||||||| RP 6306 / Repare Therap
Discovery of orally bioavailable and selective PKMYT1 inhibitor RP-6306 (Room 6C (San Diego Convention Center)) - Jan 28, 2022 - Abstract #ACSSp2022ACS_Sp_404; Optimization of cell-based potency, kinase selectivity, and ADME properties led to the identification of potent and selective inhibitors of PKMYT1 with acceptable pharmacokinetics in preclinical species. The first-in-class clinical candidate RP-6306 is currently being evaluated in Phase 1 clinical trials.
- |||||||||| lunresertib (RP-6306) / Repare Therap
Enrollment open, Combination therapy, Metastases: MAGNETIC: Study of RP-6306 With Gemcitabine in Advanced Solid Tumors (clinicaltrials.gov) - Jan 20, 2022 P1, N=104, Recruiting, The first-in-class clinical candidate RP-6306 is currently being evaluated in Phase 1 clinical trials. Not yet recruiting --> Recruiting
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