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    DRUG:

    lunresertib (RP-6306)

    i
    Other names: RP-6306, RP 6306, Manchester
    Company:
    Repare Therap
    Drug class:
    PKMYT1 inhibitor
    Related drugs:
    1m
    MYTHIC: Study of RP-6306 Alone or in Combination With RP-3500 or Debio 0123 in Patients With Advanced Solid Tumors (clinicaltrials.gov)
    P1, N=364, Recruiting, Repare Therapeutics | N=180 --> 364
    Enrollment change • Combination therapy • Metastases
    |
    lunresertib (RP-6306) • Debio 0123 • camonsertib (RP-3500)
    2ms
    GyneRep: Phase 1 Study of RP-6306 With Carboplatin and Paclitaxel in TP53 Ovarian and Uterine Cancer (clinicaltrials.gov)
    P1, N=24, Active, not recruiting, University Health Network, Toronto | Not yet recruiting --> Active, not recruiting | Initiation date: Dec 2023 --> Mar 2024
    Enrollment closed • Trial initiation date • Combination therapy
    |
    TP53 (Tumor protein P53)
    |
    TP53 mutation
    |
    carboplatin • paclitaxel • lunresertib (RP-6306)
    2ms
    MINOTAUR: Study of RP-6306 With FOLFIRI in Advanced Solid Tumors (clinicaltrials.gov)
    P1, N=36, Active, not recruiting, Repare Therapeutics | Recruiting --> Active, not recruiting | N=104 --> 36
    Enrollment closed • Enrollment change • Combination therapy • Metastases
    |
    5-fluorouracil • irinotecan • leucovorin calcium • lunresertib (RP-6306)
    4ms
    MYTHIC: Study of RP-6306 Alone or in Combination With RP-3500 in Patients With Advanced Solid Tumors (clinicaltrials.gov)
    P1, N=180, Recruiting, Repare Therapeutics | Trial completion date: Dec 2024 --> Dec 2026 | Trial primary completion date: Oct 2023 --> Jun 2026
    Trial completion date • Trial primary completion date • Combination therapy • Metastases
    |
    lunresertib (RP-6306) • camonsertib (RP-3500)
    4ms
    MAGNETIC: Study of RP-6306 With Gemcitabine in Advanced Solid Tumors (clinicaltrials.gov)
    P1, N=104, Active, not recruiting, Repare Therapeutics | Recruiting --> Active, not recruiting | Trial primary completion date: Oct 2023 --> Dec 2024
    Enrollment closed • Trial primary completion date • Combination therapy • Metastases
    |
    gemcitabine • lunresertib (RP-6306)
    5ms
    RP-6306 in Patients With Advanced Cancer (clinicaltrials.gov)
    P2, N=78, Recruiting, Canadian Cancer Trials Group
    Trial completion date • Trial primary completion date • Metastases
    |
    HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • CCNE1 (Cyclin E1) • UGT1A1 (UDP glucuronosyltransferase family 1 member A1)
    |
    TP53 mutation • KRAS mutation • HER-2 amplification • RAS mutation • CCNE1 amplification • UGT1A1*28 • UGT1A1*1*1
    |
    Herceptin (trastuzumab) • gemcitabine • 5-fluorouracil • irinotecan • leucovorin calcium • lunresertib (RP-6306)
    7ms
    GyneRep: Phase 1 Study of RP-6306 With Carboplatin and Paclitaxel in TP53 Ovarian and Uterine Cancer (clinicaltrials.gov)
    P1, N=24, Not yet recruiting, University Health Network, Toronto
    New P1 trial • Combination therapy
    |
    TP53 (Tumor protein P53)
    |
    TP53 mutation
    |
    carboplatin • paclitaxel • lunresertib (RP-6306)
    8ms
    MYTHIC: First-in-human (FIH) biomarker-driven phase I trial of PKMYT1 inhibitor lunresertib (lunre) alone and with ATR inhibitor camonsertib (cam) in solid tumors with CCNE1 amplification or deleterious alterations in FBXW7 or PPP2R1. (AACR-NCI-EORTC 2023)
    No abstract available
    P1 data
    |
    CCNE1 (Cyclin E1) • FBXW7 (F-Box And WD Repeat Domain Containing 7) • PKMYT1 (Protein Kinase Membrane Associated Tyrosine/Threonine 1)
    |
    CCNE1 amplification
    |
    lunresertib (RP-6306) • camonsertib (RP-3500)
    8ms
    MYTHIC: First-in-human (FIH) biomarker-driven phase I trial of PKMYT1 inhibitor lunresertib (lunre) alone and with ATR inhibitor camonsertib (cam) in solid tumors with CCNE1 amplification or deleterious alterations in FBXW7 or PPP2R1A* (AACR-NCI-EORTC 2023)
    No abstract available
    P1 data
    |
    CCNE1 (Cyclin E1) • FBXW7 (F-Box And WD Repeat Domain Containing 7) • PKMYT1 (Protein Kinase Membrane Associated Tyrosine/Threonine 1) • PPP2R1A (Protein Phosphatase 2 Scaffold Subunit Aalpha)
    |
    CCNE1 amplification
    |
    lunresertib (RP-6306) • camonsertib (RP-3500)
    8ms
    Retrospective baseline biomarker analyses in a first-in-human Phase 1 trial of the PKMYT1 inhibitor lunresertib (RP-6306) in pts with advanced solid tumors harboring CCNE1 amplification and/or deleterious alterations in FBXW7 or PPP2. (AACR-NCI-EORTC 2023)
    No abstract available
    P1 data • Retrospective data • Metastases
    |
    CCNE1 (Cyclin E1) • FBXW7 (F-Box And WD Repeat Domain Containing 7) • PKMYT1 (Protein Kinase Membrane Associated Tyrosine/Threonine 1)
    |
    CCNE1 amplification
    |
    lunresertib (RP-6306)
    12ms
    RP-6306 in Patients With Advanced Cancer (clinicaltrials.gov)
    P2, N=78, Recruiting, Canadian Cancer Trials Group | Not yet recruiting --> Recruiting | Initiation date: Jan 2023 --> Apr 2023
    Enrollment open • Trial initiation date • Metastases
    |
    HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • CCNE1 (Cyclin E1) • UGT1A1 (UDP glucuronosyltransferase family 1 member A1)
    |
    TP53 mutation • KRAS mutation • HER-2 amplification • RAS mutation • CCNE1 amplification • UGT1A1*28 • UGT1A1*1*1
    |
    Herceptin (trastuzumab) • gemcitabine • 5-fluorouracil • irinotecan • leucovorin calcium • lunresertib (RP-6306)
    1year
    MYTHIC: Study of RP-6306 Alone or in Combination With RP-3500 in Patients With Advanced Solid Tumors (clinicaltrials.gov)
    P1, N=180, Recruiting, Repare Therapeutics | N=120 --> 180 | Trial completion date: Apr 2024 --> Dec 2024
    Enrollment change • Trial completion date • Combination therapy • Metastases
    |
    CDK1 (Cyclin-dependent kinase 1)
    |
    lunresertib (RP-6306) • camonsertib (RP-3500)
    1year
    Tumor heterogeneity of CCNE1 copy number assessed by fluorescence in situ hybridization (FISH) in ovarian and uterine cancers and correlation with cyclin E protein expression (AACR 2023)
    Substantial intratumoral spatial heterogeneity of CCNE1 copy number when measured by FISH was observed across ovarian and uterine tumors. The potential impact of CCNE1 amplification heterogeneity, cyclin E1 protein levels and CCNE1 amplification fragment size on response to RP-6306 in preclinical models are currently being investigated and will be reported.
    CCNE1 (Cyclin E1) • PKMYT1 (Protein Kinase Membrane Associated Tyrosine/Threonine 1)
    |
    CCNE1 amplification • CCNE1 expression
    |
    lunresertib (RP-6306)
    over1year
    RP-6306 in Patients With Advanced Cancer (clinicaltrials.gov)
    P2, N=78, Not yet recruiting, Canadian Cancer Trials Group
    New P2 trial • Metastases
    |
    HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • CCNE1 (Cyclin E1) • UGT1A1 (UDP glucuronosyltransferase family 1 member A1)
    |
    TP53 mutation • KRAS mutation • HER-2 amplification • RAS mutation • CCNE1 amplification • UGT1A1*28 • UGT1A1*1*1
    |
    Herceptin (trastuzumab) • gemcitabine • 5-fluorouracil • irinotecan • leucovorin calcium • lunresertib (RP-6306)
    almost2years
    Discovery of an Orally Bioavailable and Selective PKMYT1 Inhibitor, RP-6306. (PubMed, J Med Chem)
    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.
    Journal
    |
    CCNE1 (Cyclin E1) • CDK1 (Cyclin-dependent kinase 1) • PKMYT1 (Protein Kinase Membrane Associated Tyrosine/Threonine 1)
    |
    CCNE1 amplification
    |
    lunresertib (RP-6306)
    2years
    MYTHIC: Study of RP-6306 Alone or in Combination With RP-3500 in Patients With Advanced Solid Tumors (clinicaltrials.gov)
    P1, N=120, Recruiting, Repare Therapeutics | N=60 --> 120 | Trial completion date: Jun 2023 --> Apr 2024 | Trial primary completion date: Apr 2023 --> Oct 2023
    Enrollment change • Trial completion date • Trial primary completion date • Combination therapy
    |
    CDK1 (Cyclin-dependent kinase 1)
    |
    lunresertib (RP-6306) • camonsertib (RP-3500)
    2years
    CCNE1 amplification is synthetic lethal with PKMYT1 kinase inhibition. (PubMed, Nature)
    To inhibit PKMYT1, we developed RP-6306, an orally bioavailable and selective inhibitor that shows single-agent activity and durable tumour regressions when combined with gemcitabine in models of CCNE1 amplification. 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.
    Journal • Synthetic lethality
    |
    CCNE1 (Cyclin E1) • FOXM1 (Forkhead Box M1) • CDK1 (Cyclin-dependent kinase 1) • PKMYT1 (Protein Kinase Membrane Associated Tyrosine/Threonine 1)
    |
    CCNE1 amplification • CCNE1 overexpression
    |
    gemcitabine • lunresertib (RP-6306)
    2years
    RP-6306, a novel PKMYT1 inhibitor, demonstrates synthetic lethality as monotherapy and in combination with gemcitabine in CCNE1 amplified cancer cells (AACR 2022)
    Our studies show that inhibition of PKMYT1 kinase activity impairs the growth of CCNE1 amplified cancer cell lines both in vitro and in vivo and stands to benefit cancer patients with CCNE1 amplification. A Phase I clinical trial (NCT04855656- Mythic Study) is currently underway to evaluate RP-6306 in patients with advanced solid tumors.
    Combination therapy • Synthetic lethality
    |
    CCNE1 (Cyclin E1) • CASP3 (Caspase 3) • CDK2 (Cyclin-dependent kinase 2) • CDK1 (Cyclin-dependent kinase 1) • PKMYT1 (Protein Kinase Membrane Associated Tyrosine/Threonine 1)
    |
    CCNE1 amplification
    |
    gemcitabine • lunresertib (RP-6306)
    almost3years
    A phase 1 trial to study how safe and tolerable RP-6306 is when administered in patients with certain types of cancer (clinicaltrialsregister.eu)
    P1, N=60, Repare Therapeutics
    Clinical • New P1 trial
    |
    TP53 (Tumor protein P53) • POLE (DNA Polymerase Epsilon) • CCNE1 (Cyclin E1) • FBXW7 (F-Box And WD Repeat Domain Containing 7) • CDK1 (Cyclin-dependent kinase 1)
    |
    TP53 mutation • CCNE1 amplification • TP53 expression • FBXW7 deletion
    |
    lunresertib (RP-6306)