^
    Contact us  to learn more about
    our Premium Content:  News alerts, weekly reports and conference planners
    DRUG:

    lunresertib (Debio2513)

    i
    Other names: Debio2513, RP-6306, RP 6306, Manchester, RP6306, Debio-2513
    Company:
    Debiopharm, XenoTherapeutics
    Drug class:
    PKMYT1 inhibitor
    Related drugs:
    6d
    PKMYT1 is a Targetable Vulnerability in del(17p) High-Risk Multiple Myeloma. (PubMed, Blood)
    RP-6306 also reduced tumor burden and extended survival in vivo in both xenograft and TP53-deficient syngeneic models. Collectively, our findings nominate PKMYT1 as an actionable target and support PKMYT1 inhibition as a biomarker-driven therapeutic strategy for patients with del(17p)/TP53-deficient MM.
    Journal
    |
    TP53 (Tumor protein P53) • PKMYT1 (Protein Kinase Membrane Associated Tyrosine/Threonine 1)
    |
    lunresertib (Debio2513)
    7d
    Debio 0123-106: A phase 1 trial to study how safe and tolerable Lunresertib is, alone or in Combination with RP-3500 or Debio 0123, whennadministered in patients with certain types of cancer (2023-510063-35-00)
    P1, N=63, Recruiting, Debiopharm International S.A. | N=38 --> 63
    Enrollment change
    |
    TP53 (Tumor protein P53) • POLE (DNA Polymerase Epsilon) • CCNE1 (Cyclin E1) • FBXW7 (F-Box And WD Repeat Domain Containing 7) • MUC16 (Mucin 16, Cell Surface Associated)
    |
    TP53 mutation
    |
    lunresertib (Debio2513) • camonsertib (RP-3500) • zedoresertib (Debio 0123)
    19d
    Brain metastasis from KRAS wild-type pancreatic cancer and organoid correlates: a case report. (PubMed, J Gastrointest Oncol)
    Successful generation of a BrM-derived organoid line enabled high-throughput drug screening, which recapitulated the patient's clinical resistance to standard therapies [gemcitabine/nab-paclitaxel, 5-fluorouracil (5-FU)], and showed sensitivity to afatinib, everolimus and RMC-6236...Physicians should also be aware that KRAS wild-type pancreatic cancer with atypical amplifications is likely to exhibit unique metastatic tropisms. Finally, we suggest that patient-derived organoids pharmacotyping can mirror clinical drug responses and help evaluate therapeutic avenues for patient treatment.
    Journal
    |
    KRAS (KRAS proto-oncogene GTPase) • PKMYT1 (Protein Kinase Membrane Associated Tyrosine/Threonine 1)
    |
    KRAS wild-type • RAS wild-type
    |
    Gilotrif (afatinib) • gemcitabine • 5-fluorouracil • everolimus • albumin-bound paclitaxel • lunresertib (Debio2513) • daraxonrasib (RMC-6236)
    20d
    Recent advances in the discovery of PKMYT1-targeting drugs: a patent review (2021-2025). (PubMed, Expert Opin Ther Pat)
    The rapid advancement of PKMYT1 inhibitors and degraders underscores their potential as a synthetic‑lethal therapeutic strategy for cancers with CCNE1 amplification or FBXW7 alterations. Clinical proof‑of‑concept for this approach has been established by RP‑6306 trial outcomes, while insights from this comprehensive review are expected to inform strategies addressing the current limitations in this field.
    Review • Journal
    |
    CCNE1 (Cyclin E1) • FBXW7 (F-Box And WD Repeat Domain Containing 7) • CDK1 (Cyclin-dependent kinase 1) • PKMYT1 (Protein Kinase Membrane Associated Tyrosine/Threonine 1)
    |
    lunresertib (Debio2513)
    4ms
    RP-6306 in Patients With Advanced Cancer (clinicaltrials.gov)
    P2, N=28, Completed, Canadian Cancer Trials Group | Active, not recruiting --> Completed
    Trial completion
    |
    HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • CCNE1 (Cyclin E1) • FBXW7 (F-Box And WD Repeat Domain Containing 7) • UGT1A1 (UDP glucuronosyltransferase family 1 member A1) • PPP2R1A (Protein Phosphatase 2 Scaffold Subunit Aalpha)
    |
    TP53 mutation • KRAS mutation • HER-2 amplification • RAS mutation
    |
    Herceptin (trastuzumab) • gemcitabine • 5-fluorouracil • irinotecan • leucovorin calcium • lunresertib (Debio2513) • camonsertib (RP-3500)
    5ms
    MYTHIC: Study of Lunresertib Alone or in Combination With RP-3500 or Debio 0123 in Patients With Advanced Solid Tumors (clinicaltrials.gov)
    P1, N=464, Recruiting, Debiopharm International SA | Trial completion date: Dec 2026 --> Jun 2028 | Trial primary completion date: Jun 2026 --> Dec 2027
    Trial completion date • Trial primary completion date
    |
    CCNE1 (Cyclin E1) • FBXW7 (F-Box And WD Repeat Domain Containing 7) • MUC16 (Mucin 16, Cell Surface Associated) • PPP2R1A (Protein Phosphatase 2 Scaffold Subunit Aalpha)
    |
    lunresertib (Debio2513) • camonsertib (RP-3500) • zedoresertib (Debio 0123)
    6ms
    PKMYT1 inhibition induces DNA damage and synergizes with immune checkpoint blockade in CCNE1 -amplified gastroesophageal adenocarcinoma. (PubMed, bioRxiv)
    We evaluated lunresertib (RP-6306), a selective first-in-class PKMYT1 inhibitor, in CCNE1 -amplified and wild-type GEA cell lines to define its effects on cell viability, DNA damage, and gene expression changes...In a syngeneic murine model of CCNE1 -amplified gastric cancer, we further identified that PKMYT1 inhibition induced T cell infiltration and tumor microenvironment remodeling, and synergized with anti-PD-1 therapy to drive tumor regression. Together, these results support further development of PKMYT1 inhibition in combination with PD-1 blockade for CCNE1 -amplified GEA.
    Journal • Checkpoint inhibition • PD(L)-1 Biomarker • IO biomarker
    |
    TP53 (Tumor protein P53) • CCNE1 (Cyclin E1) • PKMYT1 (Protein Kinase Membrane Associated Tyrosine/Threonine 1)
    |
    lunresertib (Debio2513)
    6ms
    GyneRep: Phase 1 Study of RP-6306 With Carboplatin and Paclitaxel in TP53 Ovarian and Uterine Cancer (clinicaltrials.gov)
    P1, N=6, Active, not recruiting, University Health Network, Toronto | N=24 --> 6 | Trial completion date: Dec 2026 --> Jan 2026 | Trial primary completion date: Dec 2026 --> Oct 2025
    Enrollment change • Trial completion date • Trial primary completion date
    |
    TP53 (Tumor protein P53)
    |
    TP53 mutation
    |
    carboplatin • paclitaxel • lunresertib (Debio2513)
    11ms
    Unraveling resistance mechanisms to the novel nucleoside analog RX-3117 in lung cancer: insights into DNA repair, cell cycle dysregulation and targeting PKMYT1 for improved therapy. (PubMed, J Exp Clin Cancer Res)
    By integrating CRISPR-Cas9 with functional assays and transcriptomics, our study established a framework for decoding resistance mechanisms and highlights potential therapeutic strategies to enhance RX-3117 efficacy in NSCLC. We demonstrated for the first time that aberrant DNA repair and cell cycle dysregulation led resistance, identifying PKMYT1 as a promising target.
    Journal
    |
    PKMYT1 (Protein Kinase Membrane Associated Tyrosine/Threonine 1)
    |
    gemcitabine • lunresertib (Debio2513) • roducitabine (PCS3117)
    11ms
    RP-6306 in Patients With Advanced Cancer (clinicaltrials.gov)
    P2, N=28, Active, not recruiting, Canadian Cancer Trials Group | Recruiting --> Active, not recruiting | N=78 --> 28
    Enrollment closed • Enrollment change
    |
    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
    |
    Herceptin (trastuzumab) • gemcitabine • 5-fluorouracil • irinotecan • leucovorin calcium • lunresertib (Debio2513) • camonsertib (RP-3500)
    12ms
    MINOTAUR: Study of RP-6306 With FOLFIRI in Advanced Solid Tumors (clinicaltrials.gov)
    P1, N=38, Terminated, Repare Therapeutics | Trial completion date: Nov 2026 --> Feb 2025 | Active, not recruiting --> Terminated | Trial primary completion date: Jul 2026 --> Feb 2025; Sponsor decided to terminate the study
    Trial completion date • Trial termination • Trial primary completion date
    |
    5-fluorouracil • irinotecan • leucovorin calcium • lunresertib (Debio2513)
    12ms
    MAGNETIC: Study of RP-6306 With Gemcitabine in Advanced Solid Tumors (clinicaltrials.gov)
    P1, N=67, Terminated, Repare Therapeutics | N=104 --> 67 | Trial completion date: Apr 2025 --> Aug 2024 | Active, not recruiting --> Terminated | Trial primary completion date: Dec 2024 --> Aug 2024; Sponsor decided to terminate the study
    Enrollment change • Trial completion date • Trial termination • Trial primary completion date
    |
    gemcitabine • lunresertib (Debio2513)