camonsertib (RP-3500) / Repare Therap - LARVOL DELTA

Morpheus Lung: A Study Of Multiple Immunotherapy-Based Treatment Combinations In Participants With Metastatic Non-Small Cell Lung Cancer (Morpheus- Non-Small Cell Lung Cancer) (clinicaltrials.gov) - P1/2 | N=314 | Active, not recruiting | Sponsor: Hoffmann-La Roche | Trial completion date: Nov 2026 ➔ Nov 2025

Trial completion date • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • PD-L1

Repare Therapeutics Enters into Definitive Agreement to be Acquired by XenoTherapeutics, Inc. (Businesswire) - "Transaction expected to close in the first quarter of 2026....$112.6 million in cash and cash equivalents and marketable securities as of September 30, 2025, as compared to $109.5 million at June 30, 2025....As permitted under the Arrangement Agreement, Repare continues to endeavor to license or dispose of its product candidates and/or intellectual property related to its (i) RP-3467 and Polθ program, (ii) RP-1664 program, (iii) RP-3500 (Camonsertib) program, and/or (iv) any other of the Company’s product candidates or research programs."

M&A • Solid Tumor

Coronado CLL: A Phase Ib/II Trial of Combination Rp-3500 and Olaparib in DNA Damage Repair Pathway Deficient Relapsed/Refractory Chronic Lymphocytic Leukemia (ASH 2023) - P1/2 | "With a planned 24 evaluable pts in phase II, the target ORR will be 60%, which was selected due to a recent phase I/II study of pirtobrutinib enrolling a similar CLL pt population demonstrating an ORR of the drug ~63%. ORR will be summarized by the observed proportion and an exact one-sided 95% confidence interval (Clopper-Pearson method). With 24 evaluable pts, the lower bound of the confidence interval will be approximately 17-20% below the observed proportion for observed ORR near 60%, which is an acceptable level of precision in a dose expansion cohort."

IO biomarker • P1/2 data • Ataxia • Breast Cancer • Chronic Lymphocytic Leukemia • Hematological Malignancies • Immunology • Leukemia • Movement Disorders • Oncology • Ovarian Cancer • Primary Immunodeficiency • Solid Tumor • BRCA1 • BRCA2 • POT1 • SF3B1 • TP53

A Study of RP-3500 in Combination With Standard Radiation Therapy in People With Solid Tumor Cancer (clinicaltrials.gov) - P1/2 | N=84 | Recruiting | Sponsor: Memorial Sloan Kettering Cancer Center | Trial completion date: Sep 2025 ➔ Sep 2026 | Trial primary completion date: Sep 2025 ➔ Sep 2026

Trial completion date • Trial primary completion date • Oncology • Palliative care • Solid Tumor • ATM

ATTACC: Study of RP-3500 (Camonsertib) With Niraparib or Olaparib in Advanced Solid Tumors (clinicaltrials.gov) - P1/2 | N=156 | Terminated | Sponsor: Repare Therapeutics | Trial completion date: Dec 2025 ➔ Nov 2024 | Active, not recruiting ➔ Terminated | Trial primary completion date: Mar 2025 ➔ Nov 2024; Sponsor decided to terminate study early therefore, the Phase 2 portion was not conducted

Trial completion date • Trial primary completion date • Trial termination • Oncology • Solid Tumor

ATR Inhibition as a Radiosensitization Strategy in Naturally Occurring Feline Head and Neck Squamous Cell Carcinoma (ASTRO 2025) - "Preliminary data suggest that camonsertib enhances radiosensitivity in FOSCC, with promising in vitro and in vivo clinical findings. This clinical trial design mirrors a pending phase I clinical trial for humans with recurrent head and neck squamous cell carcinoma, with the added benefit of tissue acquisition after the first RT dose in the feline trial. Further enrollment, follow-up, and correlative studies will clarify camonsertib's therapeutic potential as a radiosensitizer in feline and comparative oncology."

Head and Neck Cancer • Oncology • Oropharyngeal Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

TRESR: Study of RP-3500, Camonsertib, in Advanced Solid Tumors (clinicaltrials.gov) - P1/2 | N=276 | Completed | Sponsor: Repare Therapeutics | Trial completion date: Dec 2025 ➔ Jun 2025 | Active, not recruiting ➔ Completed

Trial completion • Trial completion date • Solid Tumor

Testing the Addition of an Anti-Cancer Drug, Camonsertib, to Radiation Therapy for Recurrent Head and Neck Squamous Cell Carcinoma (clinicaltrials.gov) - P1 | N=39 | Not yet recruiting | Sponsor: National Cancer Institute (NCI)

New P1 trial • Tumor mutational burden • Head and Neck Cancer • Hypopharyngeal Cancer • Laryngeal Cancer • Oncology • Oral Cancer • Oropharyngeal Cancer • Otorhinolaryngology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Squamous Cell Skin Cancer

RP-6306 in Patients With Advanced Cancer (clinicaltrials.gov) - P2 | N=28 | Active, not recruiting | Sponsor: Canadian Cancer Trials Group | Recruiting ➔ Active, not recruiting | N=78 ➔ 28

Enrollment change • Enrollment closed • P53mut • Breast Cancer • Colorectal Cancer • Endometrial Cancer • Esophageal Cancer • Gastric Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Triple Negative Breast Cancer • CCNE1 • HER-2 • KRAS • TP53 • UGT1A1

Exceptional response to the ATR inhibitor, camonsertib, in a patient with ALT+ metastatic melanoma. (PubMed, NPJ Precis Oncol) - "Here we describe a case of confirmed clinical and molecular response to pharmacological ATR inhibition through camonsertib, in a patient with ALT+ metastatic melanoma. To our knowledge, this is the first clinical report of synthetic lethal targeting of a confirmed ALT+ tumor with an ATR inhibitor."

Journal • Ataxia • Immunology • Melanoma • Movement Disorders • Oncology • Primary Immunodeficiency • Solid Tumor

IND.241: A Canadian Cancer Trials Group liquid-biopsy informed platform trial to evaluate treatment in CDK4/6-inhibitor resistant ER+/HER2- metastatic breast. (ASCO 2025) - P2 | "Substudy B is evaluating lunresertib (PKMYT1 inhibitor) + gemcitabine in patients +/-CCNE1 overexpression / amplification. Substudy C is evaluating niraparib (PARP inhibitor) + fulvestrant (ET) in patients +/- alterations in BRCA1/2 (germline/somatic) or PALB2 (germline)...Substudy D, which has recently been added, is evaluating lunresertib + camonsertib (ATR inhibitor) in patients +/- CCNE1 overexpression/amplification, FBXW7 or PPP2R1A alterations. Additional substudies are in development for inclusion in this platform trial."

Biopsy • Liquid biopsy • Metastases • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Oncology • BRCA1 • BRCA2 • CCNE1 • ER • FBXW7 • HER-2 • PALB2 • PKMYT1 • PPP2R1A

The cold immunological landscape of ATM-deficient cancers. (PubMed, J Immunother Cancer) - "ATM deficiency, while compromising DNA repair and enhancing sensitivity to radiation and ATR inhibition, does not increase tumor antigenicity or immunogenicity. Altogether, our results have important implications for the design of novel combination therapies for ATM null tumors and highlight the importance of antigenicity in the immunological consequences of defective DNA repair."

IO biomarker • Journal • Ataxia • Breast Cancer • Colorectal Cancer • Immune Modulation • Immunology • Lung Cancer • Movement Disorders • Oncology • Pancreatic Cancer • Primary Immunodeficiency • Solid Tumor • Triple Negative Breast Cancer • ATM

Molecular architecture and inhibition mechanism of human ATR-ATRIP. (PubMed, Sci Bull (Beijing)) - "Here, we determined the cryo-EM structures of the human ATR-ATRIP complex in the presence of VE-822 and RP-3500, two ATR inhibitors currently in Phase II clinical trials, achieving an overall resolution of approximately 3 Å. The binding and selectivity of RP-3500 depend on two bound water molecules, which may be further enhanced by the substitution of these bound waters. Our study provides a structural framework for understanding ATR regulation and holds promise for assisting future efforts in rational drug design targeting ATR."

Journal • Ataxia • Immunology • Movement Disorders • Oncology • Primary Immunodeficiency

OncoKBTM, MSK's precision oncology knowledge base: 2024 updates (AACR 2025) - "OncoKB promoted BRAF fusions to Level 1 following inclusion as patient eligibility criteria in the FDA drug label for tovorafenib (low-grade glioma). Additionally, OncoKB included KRAS G12C in colorectal cancer and IDH1 mutations in myelodysplastic syndromes as Level 1 following FDA approval of adagrasib + cetuximab and ivosidenib, respectively...Lastly, novel biomarkers including FBXW7 and PPP2R1A alterations (endometrial and ovarian cancer), SMARCA4 mutations (non-small cell lung cancer and esophageal adenocarcinoma) and MTAP deletions (all solid tumors) were included in OncoKB based on compelling preclinical and emerging clinical evidence in association with lunresertib + camonsertib, PRT3789, and AMG193 and MRTX1719, respectively...OncoKB also implemented major software updates to support data integration into the EPIC platform. Future OncoKB efforts are focused on whole genome/exome curation, inclusion of biomarkers for non-NGS-based precision oncology therapies,..."

Tumor mutational burden • Brain Cancer • CNS Tumor • Colorectal Cancer • Endometrial Cancer • Esophageal Adenocarcinoma • Esophageal Cancer • Glioma • Hematological Malignancies • Lung Cancer • Microsatellite Instability • Myelodysplastic Syndrome • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Small Intestinal Carcinoma • Solid Tumor • BRAF • FBXW7 • IDH1 • KRAS • MSI • MTAP • POLD1 • PPP2R1A • SMARCA4 • TMB

Decitabine (DAC) induces a DNA damage response (DDR) and synergizes with replication checkpoint inhibitors in acute myeloid leukemia (AML) (AACR 2025) - "(nM)Molm13 (TP53WT)Molm13 (TP53-/-)U937 (TP53G187fs*/-)KG1a (TP53V225fs*/-)Primary AML (TP53WT orTP53MT)UnitsDecitabineDNMT16.25 – 20025 ± 11350 ± 260310 ± 1806.1 ± 1.6NDEC50, nM (mean, SD)CeralasertibATR250 – 5000.93 (0.66 – 1.24)0.90 (0.84 – 0.96)0.15 (0.08 – 0.21)0.74 (0.63 – 1.02)0.66 (0.43 – 2.43)CI with decitabine (median, IQR) CamonsertibATR10 – 1000.27 (0.19 – 0.59)0.24 (0.22 – 0.34)0.34 (0.21 – 0.39)NDNDPrexasertibCHK1/21.0 – 6.00.89 (0.82 – 1.06)0.78 (0.68 – 0.90)0.95 (0.93 – 1.08)ND0.88 (0.29 – 1.28)MK-8776CHK1250 – 1,0000.57 (0.48 – 0.80)0.76 (0.73 – 1.19)0.89 (0.57 – 1.39)NDNDRabusertibCHK1600 – 1,000NDNDND0.51 (0.48 – 0.56)NDAdavosertibWEE1100 – 4000.70 (0.63 – 1.11)0.99 (0.78 – 1.14)0.67 (0.60 – 0.74)0.67 (0.37 – 0.93)0.65 (0.43 – 0.88)Table 1. U937 data were replicated using annexin V. Prexasertib showed no activity in KG1a cells (suggesting drug efflux) requiring the use of the alternate CHK1 inhibitor, rabusertib. Abbreviations: ATR,..."

Checkpoint inhibition • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • Solid Tumor • ANXA5 • ATR • DNMT1

IND.241: A Canadian cancer trials group liquid-biopsy informed platform trial to evaluate treatment in CDK4/6-inhibitor resistant ER+/HER2- metastatic breast cancer (AACR 2025) - "Substudy B is evaluating lunresertib (PKMYT1 inhibitor) + gemcitabine in patients +/-CCNE1 overexpression / amplification. Substudy C is evaluating niraparib (PARP inhibitor) + fulvestrant (ET) in patients +/- alterations in BRCA1/2 (germline/somatic) or PALB2 (germline)... IND.241 employs a biomarker-driven platform trial designed to evaluate CDK4/6i resistant ER+/HER2- MBC, using non-invasive ctDNA tumor genotyping to select patients for biomarker-driven substudies with the goal of defining the ctDNA landscape across 1L to 3L treatments."

Biopsy • Liquid biopsy • Metastases • Breast Cancer • Estrogen Receptor Positive Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • BRCA1 • BRCA2 • CCNE1 • ER • FBXW7 • HER-2 • PALB2 • PKMYT1 • PPP2R1A

Discovery of selective and orally bioavailable PKMYT1 inhibitor: characterization of anti-tumor activities as single and dual agents (AACR 2025) - "Preclinical validation of this hypothesis demonstrated that combining PKMYT1 inhibitors with ATR inhibitors, such as prexasertib and RP-3500, resulted in enhanced antitumor activity in CCNE1-amplified cancer models. Additionally, we observed synergistic effects when combining PKMYT1 inhibitors with standard-of-care chemotherapies that induce DNA damage, such as gemcitabine and hydroxyurea...In conclusion, our study underscores the therapeutic potential of selective PKMYT1 inhibitors in CCNE1-amplified cancers and provides a strong rationale for their combination with ATR inhibitors and DNA-damaging chemotherapies. These findings support the continued development and clinical evaluation of PKMYT1 inhibitors as a novel approach to cancer treatment."

Esophageal Cancer • Gastric Cancer • Gastroesophageal Cancer • Oncology • Solid Tumor • CCNE1 • CDK1 • PKMYT1

Rb loss-related DNA damage repair deficiency mediates the synthetically lethal effect of ATR/PKMYT1 co-inhibition in TNBC and CDK4/6i-resistant ER+ breast cancer (AACR 2025) - "By investigating the synthetic lethality of ATR/PKMYT1 co-inhibition, we aimed to identify biomarkers predictive of treatment response, specifically examining Rb status and its effect on DNA damage repair mechanisms. The study tested the combination of ATR inhibitor (RP3500) and PKMYT1 inhibitor (RP6306) in TNBC and ER-positive parental and palbociclib-resistant breast cancer cell lines, as well as in patient-derived xenograft (PDX) models. ATR and PKMYT1 co-inhibition is a promising therapeutic strategy for TNBC and CDK4/6i-resistant breast cancer. The synthetic lethality of this combination is enhanced in Rb-deficient models, where Rb1 loss impairs DNA damage repair capabilities, amplifying the anti-tumor effects."

Synthetic lethality • Breast Cancer • Estrogen Receptor Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • CDK4 • ER • PKMYT1 • RB1

Efficacy and safety of the combination PKMYT1-inhibitor lunresertib and ATR-inhibitor camonsertib in patients with ovarian and endometrial cancers: Phase I MYTHIC study (NCT04855656) (AACR 2025) - P1 | "Lunre + cam is a tolerable and effective oral combination therapy of two novel targeted agents in molecularly-selected OC and EC with poor prognostic features and no approved targeted therapies. Enrollment closed in Dec 2024, the presentation will provide updated data for potential late-stage clinical development."

Clinical • P1 data • Carcinosarcoma • Endometrial Cancer • Oncology • Ovarian Cancer • Sarcoma • Solid Tumor • CCNE1 • CDK1 • FBXW7 • PKMYT1 • PPP2R1A

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

Targeting CCNE1 amplified ovarian and endometrial cancers by combined inhibition of PKMYT1 and ATR. (PubMed, Nat Commun) - "Mechanistically, low doses of RP-6306 with RP-3500 increase CDK1 activation more so than monotherapy, triggering rapid and robust induction of premature mitosis, DNA damage, and apoptosis in a CCNE1-dependent manner. These findings suggest that targeting CDK1 activity by combining RP-6306 with RP-3500 is an effective therapeutic approach to treat CCNE1-amplifed OVCAs and EMCAs."

Journal • Endometrial Cancer • Oncology • Ovarian Cancer • Solid Tumor • CCNE1 • CDK1 • PKMYT1

TalaCom: Phase Ib investigator-initiated trial combining talazoparib and axitinib in patients with DNA damage response mutated cancers or BRCA1/2 wildtype ovarian cancer incorporating prospective intrapatient dose titration (ESMO-TAT 2025) - P1 | "22/24 (92%) evaluable pts achieved RECIST SD or PR; 13/24 (54%) had tumor regressions, and 5/24 (21%) achieved RECIST PRs: 2 pts with BRCA2m HGSOC (one who progressed on prior olaparib, saruparib and camonsertib); 1 pt with BRCA2m peritoneal mesothelioma; 2 pts with mCRPC without DDR mutations (one who progressed on prior olaparib). The combination of axi + tala was generally manageable with durable antitumor activity in heavily pretreated HGSOC and CRPC pts, including pts who progressed on prior PARPi. Biomarker and PK analyses are ongoing."

Clinical • P1 data • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • High Grade Serous Ovarian Cancer • Mesothelioma • Oncology • Ovarian Cancer • Peritoneal Mesothelioma • Prostate Cancer • Solid Tumor • BRCA • BRCA1 • BRCA2 • BRIP1 • CDK12 • CHEK2 • PALB2 • RAD51C

TRESR: Study of RP-3500, Camonsertib, in Advanced Solid Tumors (clinicaltrials.gov) - P1/2 | N=285 | Active, not recruiting | Sponsor: Repare Therapeutics | Recruiting ➔ Active, not recruiting

Enrollment closed • Oncology • Solid Tumor

Morpheus Lung: A Study Of Multiple Immunotherapy-Based Treatment Combinations In Participants With Metastatic Non-Small Cell Lung Cancer (Morpheus- Non-Small Cell Lung Cancer) (clinicaltrials.gov) - P1/2 | N=314 | Active, not recruiting | Sponsor: Hoffmann-La Roche | N=675 ➔ 314

Enrollment change • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • PD-L1

RP-6306 in Patients With Advanced Cancer (clinicaltrials.gov) - P2 | N=78 | Recruiting | Sponsor: Canadian Cancer Trials Group | Trial completion date: Jun 2025 ➔ May 2026 | Trial primary completion date: Dec 2024 ➔ Dec 2025

Trial completion date • Trial primary completion date • Breast Cancer • Colorectal Cancer • Endometrial Cancer • Esophageal Cancer • Gastric Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Triple Negative Breast Cancer • CCNE1 • HER-2 • KRAS • TP53 • UGT1A1