Debiopharm launches phase 1 research in small cell lung cancer with Wee1 inhibitor Debio 0123 to outsmart DDR in small cell lung cancer
- Category: Small Molecules
- Published on Wednesday, 31 May 2023 10:42
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- Debiopharm combines its potent WEE1-inhibitor Debio 0123 with standard-of-care therapy to short-circuit DNA damage repair (DDR) in adults with recurrent or progressive small cell lung cancer (SCLC).
- The first patient dosed at Vall d'Hebron Hospital (Barcelona, Spain), was announced for this Phase 1 dose-escalation and expansion study evaluating Debio 0123 in combination with carboplatin and etoposide in participants with recurring or progressive, platinum-sensitive SCLC.
LAUSANNE, Switzerland I May 30, 2023 I Debiopharm (www.debiopharm.com), a privately-owned, Swiss-based biopharmaceutical company aiming to establish tomorrow's standard-of-care to cure cancer and infectious diseases, today announced the first patient dosed in its open-label, multicenter, Phase 1 study evaluating Debio 0123, an oral, potent, highly selective and brain penetrant WEE1 inhibitor, in combination with carboplatin and etoposide in patients with recurrent or progressive SCLC following standard platinum-based chemotherapy. This Phase 1 study, NCT05815160 (Debio 0123-SCLC-104), comprises two parts, namely a dose escalation phase to identify the recommended dose and an expansion phase, to characterize the safety, tolerability, and initial signal of antitumoral activity of Debio 0123 in combination with carboplatin and etoposide in this patient population.
SCLC is a highly aggressive, hard-to-treat cancer with poor prognosis, representing 15% of all lung cancers. It is characterized by an extraordinarily high proliferative rate, leading to early metastasis, most of which are already present at the time of diagnosis.1 Moreover, SCLC carries a massive variety of structural mutations and cell populations inside the tumor.1 This diversity in cell populations is known to play a critical role in tumor evolution, metastasis, and acquired resistance to available therapies. In the attempt to find new therapies, targeting the DDR pathway has shown great promise when combined with DNA-damaging agents such as carboplatin and etoposide.
The Debio 0123 program originates from a growing awareness of DDR inhibition in fighting life-threatening cancers. Optimizing efficacy, while preserving safety are key elements that Debiopharm is eager to assess throughout the clinical development of Debio 0123. With the fruition of these factors, Debio 0123 could become the first choice WEE1 inhibitor.
"Small cell lung cancer is the most aggressive type of lung cancer, and frequently presents with metastatic disease. Despite initial responses to front-line therapy these are typically transient, and survival at 5 years is infrequent. With this program we hope to show that Debio 0123 combined with one of the current standard of care treatments may extend the lives of recurrent small cell lung cancer patients." Dr. Luis Paz-Ares Rodríguez, Coordinating Investigator.
"This combination might succeed in strategically enhancing antitumoral activity and delay the resistance to carboplatin and etoposide combination in patients with recurrent SCLC." expressed Dr. Esteban Rodrigo Imedio, Senior Medical Director, Oncology Research & Development, Debiopharm.
About Small Cell Lung Cancer (SCLC)
Lung cancer is the leading cause of cancer mortality worldwide with a yearly estimate of 250,000 new cases and 200,000 deaths globally.1 SCLC is most prevalent in men over 70 years of age, however the proportion of cases of women has risen over the past 50 years due to a popularization of tobacco consumption.1 SCLC, an aggressive high-grade malignant epithelial tumor, is deadly, highly metastatic, and highly mutagenic.1 Because of these traits and despite 30 years of clinical trials designed to improve therapies for SCLC, the outcomes for this disease still remain poor with a median overall survival from diagnosis of up to 13 months in patients receiving standard of care.2
About Debio 0123
Debio 0123 is a brain-penetrant, highly selective WEE1 kinase inhibitor. WEE1 is a key regulator of the G2/M and S phase checkpoints, activated in response to DNA damage, allowing cells to repair their DNA before resuming their cell cycle. WEE1 inhibition, particularly in combination with DNA damaging agents, induces an overload of DNA breaks. In conjunction with abrogation of other checkpoints such as G1, the compound pushes the cells through cycle without DNA repair, promoting mitotic catastrophe and inducing apoptosis of cancer cells. Currently in research for solid tumors in monotherapy and combination, Debio 0123 is being developed to respond to high unmet needs of patients living with the burden of difficult-to-treat cancers.
About DNA-Damage Repair (DDR)
When cells have damaged DNA, they need to undergo a repair process called DDR to be able to survive. Cancer cells use their hyperactive DDR response to divide and grow uncontrollably, which promotes cancer expansion. Inhibition of DDR, particularly in combination with other anticancer agents, induces an overall arrest in the uncontrollable cancer cell cycle. This ultimately activates a self-destruction program in cancer cells. DDR inhibitors such as Debiopharm's WEE1 and USP1 inhibitors, are being tested in clinical and preclinical studies.
Debiopharm's commitment to patients
Debiopharm aims to develop innovative therapies that target high unmet medical needs in oncology and bacterial infections. Bridging the gap between disruptive discovery products and real-world patient reach, we identify high-potential compounds and technologies for in-licensing, clinically demonstrate their safety and efficacy, and then select large pharmaceutical commercialization partners to maximize patient access globally.
For more information, please visit www.debiopharm.com
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 Rudin, C.M., Brambilla, E., Faivre-Finn, C. et al. Small-cell lung cancer. Nat Rev Dis Primers 7, 3 (2021). https://doi.org/10.1038/s41572-020-00235-0
 Paz-Ares, Luis et al. "Durvalumab plus platinum-etoposide versus platinum-etoposide in first-line treatment of extensive-stage small-cell lung cancer (CASPIAN): a randomised, controlled, open-label, phase 3 trial." Lancet (London, England) vol. 394,10212 (2019): 1929-1939. doi:10.1016/S0140-6736(19)32222-6
SOURCE: Debiopharm International