zedoresertib (Debio 0123) / Almac Discovery, Debiopharm - LARVOL DELTA

Expansion data disclosure of the phase 1 trial of WEE1 inhibitor zedoresertib in patients with advanced solid tumors (ESMO 2026) - No abstract available

Clinical • Metastases • P1 data • Oncology • Solid Tumor

Dose escalation of Debio 0123 (zedoresertib) plus temozolomide (TMZ) in patients (pts) with recurrent or progressive glioblastoma (GBM) (ESMO 2026) - No abstract available

Clinical • Brain Cancer • Glioblastoma • Oncology • Solid Tumor

WEE1 kinase in cancer: Molecular mechanisms and inhibitor insights. (PubMed, EXCLI J) - "We have also summarized the clinical development of major WEE1 inhibitors such as adavosertib, azenosertib (ZN-c3), and Debio 0123. See also the graphical abstract(Fig. 1)."

Journal • Review • Oncology • Targeted Protein Degradation • CDK1 • TP53

Dose expansion of Debio 0123 (zedoresertib) plus temozolomide in patients with recurrent or progressive glioblastoma (SNO 2026) - No abstract available

Clinical • Brain Cancer • Glioblastoma • Solid Tumor

First data disclosure of the Phase I trial of the first in class combination of WEE1 inhibitor zedoresertib with PKMYT1 inhibitor lunresertib in patients with advanced solid tumors harboring CCNE1, FBXW7, or PPP2R1A genomic alterations (AACR 2026) - P1 | "We report the first disclosure of clinical data of the first-in-field synthetic lethal combination of WEE1 and PKMYT1 inhibitors in a molecularly defined pt population. The safety profile of zedo and lunre was expected and manageable. Promising antitumor activity was observed in pts with CCNE1 amp or FBXW7 mut solid tumors, especially pts with OC."

Clinical • Metastases • P1 data • Oncology • Ovarian Cancer • Solid Tumor • CCNE1 • FBXW7 • MUC16 • PKMYT1 • PPP2R1A

A Study to Evaluate Safety and Preliminary Anti-tumor Activity of Debio 0123 as Monotherapy in Adult Participants With Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=93 | Terminated | Sponsor: Debiopharm International SA | N=66 ➔ 93

Enrollment change • Monotherapy • Oncology • Solid Tumor • CCNE1

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 (clinicaltrialsregister.eu) - P1 | N=63 | Recruiting | Sponsor: Debiopharm International S.A. | N=38 ➔ 63

Enrollment change • Oncology • Solid Tumor • CCNE1 • FBXW7 • MUC16 • POLE • TP53

Debio 0123 (zedoresertib), a selective WEE1 inhibitor, in combination with carboplatin in adult patients with platinum-resistant ovarian cancer: Expansion part of the Debio0123-101 phase 1 study. (ASCO 2026) - P1 | "Debio 0123, combined with carboplatin, has a manageable safety profile at the tested dose of 520 mg; the combination showed signals of antitumor activity in pts with PROC."

Clinical • Combination therapy • P1 data • Platinum resistant • Epithelial Ovarian Cancer • Fallopian Tube Cancer • Neutropenia • Oncology • Ovarian Cancer • Peritoneal Cancer • Solid Tumor • Thrombocytopenia

A Study to Evaluate Safety and Preliminary Anti-tumor Activity of Debio 0123 as Monotherapy in Adult Participants With Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=66 | Terminated | Sponsor: Debiopharm International SA | Active, not recruiting ➔ Terminated; This trial was concluded for strategic reasons.

Monotherapy • Trial termination • Oncology • Solid Tumor • CCNE1

Debio 0123, a WEE1 kinase inhibitor: Phase 1 results from dose escalation in patients with advanced solid tumors. (PubMed, Eur J Cancer) - "Debio 0123 demonstrated a manageable toxicity profile, exhibited linear pharmacokinetics and showed target engagement at doses ≥200 mg. Given the response observed in a subset of this heavily pre-treated population, results support further investigation of Debio 0123 in selected indications."

Journal • P1 data • Fatigue • Oncology • Solid Tumor • CDK1

Debio 0123-SCLC-104: Debio 0123 in Combination With Carboplatin and Etoposide in Adult Participants With Small Cell Lung Cancer That Recurred or Progressed After Previous Standard Platinum-Based Therapy (clinicaltrials.gov) - P1 | N=34 | Terminated | Sponsor: Debiopharm International SA | Active, not recruiting ➔ Terminated; The trial was concluded for strategic reasons.

Trial termination • Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor

Debiopharm to Unveil New Pre-Clinical and Clinical Research Advances in DDR Inhibition, Dual Payload ADCs, and AI-Driven Biomarkers at AACR 2026 (PharmiWeb) - "Preliminary clinical results of the MYTHIC study will be presented, revealing for the first time data of the combination of WEE1 and PKMYT1 inhibition (zedoresertib and lunresertib) for the treatment of solid tumors with specific genetic alterations...A major highlight of this year’s conference participation is the first clinical data disclosure from the MYTHIC Study (NCT04855656), a Phase I trial evaluating the combination of Debiopharm’s WEE1 inhibitor, zedoresertib (Debio 0123), with the PKMYT1 inhibitor lunresertib (Debio 2513) in patients with advanced solid tumors harboring CCNE1, FBXW7, or PPP2R1A genomic alterations."

P1 data • Preclinical • Gynecologic Cancers • Solid Tumor

AACR: Zedoresertib and lunresertib combination shows promising antitumor activity (Newswise) - "The overall disease control rate for 54 evaluable patients across all dosing levels was 68.5%. In 51 patients with target lesions, 26 showed tumor shrinkage and 10 patients achieved a radiological response. Among patients with advanced ovarian cancers harboring CCNE1 amplification, FBXW7 or PPP2R1A mutations, 80% showed consistent tumor shrinkage, with durable responses observed. At least 10 patients (37%) remained on treatment for more than 16 weeks, and five patients (18.5%) remained on treatment for longer than 32 weeks. The molecular response rate (MRR) was 47% for all patients across all dose levels. In patients with advanced ovarian cancer, the MRR was 67%."

P1 data • Ovarian Cancer

The WEE1 inhibitor Debio 0123 is synergistic with the PKMYT1 inhibitor lunresertib in preclinical models of ovarian and breast cancer (AACR 2025) - "Lunresertib (RP6306) is a selective and potent PKMYT1 inhibitor currently in phase 1 clinical studies as a monotherapy or in combination. These results demonstrate, in preclinical models of ovarian and breast cancer, the WEE1 inhibitor, Debio 0123, is synergistic with the PKMYT1 inhibitor, lunresertib, and consistently leads to deep and sustained regressions in vivo."

Preclinical • Breast Cancer • Oncology • Ovarian Cancer • Solid Tumor • PKMYT1

Debiopharm...announced that the U.S. Food and Drug Administration (FDA) has granted Fast Track designation to the combination of its PKMYT1 inhibitor, lunresertib (Debio2513), and its WEE1 inhibitor, zedoresertib (Debio 0123). (Businesswire) - "The designation is for the treatment of adult patients with CCNE1 amplified, or a deleterious mutation in either FBXW7 or PPP2R1A, platinum-resistant/refractory ovarian cancer."

Fast track • Platinum resistant • Ovarian Cancer • Refractory Ovarian Cancer

Simulation driven identification of combinations for the WEE1 inhibitor Debio 0123 results in synergistic effect with cabozantinib validated in vivo (AACR 2024) - "We demonstrated that an in silico computational approach to model cancer signalling pathways can complement conventional screening methodologies to identify novel, clinically actionable combination opportunities for Debio 0123."

Preclinical • Genito-urinary Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor

Anti-tumor activity of Debio 0123 in combination with sacituzumab govitecan in preclinical models of breast cancer (AACR 2024) - "These results demonstrate that Debio 0123 synergizes with, and significantly improves breast cancer tumor cell response to, SG regardless of TROP2 expression levels (both in vitro and in vivo), leading to complete regressions and inhibition of metastasis. Collectively these data support Debio 0123 in combination with SG could be a potential therapeutic approach for improving responses in patients with breast cancer."

Combination therapy • Preclinical • Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • ER • TACSTD2

Impact of food and high gastric pH on the bioavailability of the WEE1 inhibitor Debio 0123 assessed in a phase 1 dose escalation study (AACR 2024) - P1 | "In order to adequately inform drug dosing in clinical trials, effects of food and high gastric pH on D0123 bioavailability were studied over three cycles in patients treated in the dose escalation of a Phase 1 study of D0123 in combination with Carboplatin (CTID NCT03968653).D0123 was given on Days 1-3 and 8-10 of each 21-day cycle in combination with carboplatin on Day 1. In contrast, food intake has a limited impact on drug absorption, at all doses tested. Furthermore, D0123 administration with food may increase treatment convenience and tolerability, leading to its implementation in other D0123 trials."

P1 data • Head and Neck Cancer • Oncology • Oral Cancer • Solid Tumor

Biology-driven, machine learning-based development of a biomarker to predict response to WEE1 inhibitor Debio 0123 (AACR 2025) - "This biology-driven, machine learning-based classifier predicts response to Debio 0123 in patient derived organoid and xenograft models at an accuracy significantly greater than that of a dummy model and serves as a basis for further optimization and retrospective analyses of Debio 0123 clinical studies."

Biomarker • Machine learning • Oncology • TP53

A Study to Evaluate Safety and Preliminary Anti-tumor Activity of Debio 0123 as Monotherapy in Adult Participants With Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=66 | Active, not recruiting | Sponsor: Debiopharm International SA | N=155 ➔ 66 | Trial completion date: Jun 2027 ➔ Apr 2026

Enrollment change • Monotherapy • Trial completion date • Oncology • Solid Tumor • CCNE1

Pharmacological WEE1 inhibition as a strategy to overcome cisplatin resistance in non-seminoma testicular cancer: insights from preclinical models. (PubMed, Sci Rep) - No abstract available

Journal • Preclinical • Genito-urinary Cancer • Germ Cell Tumors • Oncology • Solid Tumor • Testicular Cancer

A Study to Evaluate Safety and Preliminary Anti-tumor Activity of Debio 0123 as Monotherapy in Adult Participants With Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=155 | Active, not recruiting | Sponsor: Debiopharm International SA | Trial primary completion date: Jan 2026 ➔ Apr 2026

Monotherapy • Trial primary completion date • Oncology • Solid Tumor • CCNE1

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 | Sponsor: 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 • Ovarian Cancer • Prostate Cancer • Solid Tumor • CCNE1 • FBXW7 • MUC16 • PPP2R1A

WIN-B: Clinical Study to Evaluate Debio0123 + Sacituzumab Govitecan Combination in TNBC or HR+/HER2- Advanced Breast Cancer (clinicaltrials.gov) - P1/2 | N=76 | Active, not recruiting | Sponsor: MedSIR | Recruiting ➔ Active, not recruiting

Enrollment closed • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer

Debio 0123-101: Study of Oral Debio 0123 in Combination With Carboplatin in Participants With Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=76 | Terminated | Sponsor: Debiopharm International SA | Trial completion date: Nov 2027 ➔ Oct 2025 | Active, not recruiting ➔ Terminated | Trial primary completion date: Nov 2027 ➔ Oct 2025; This trial was concluded for strategic reasons.

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