- 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,
May 30, 2023 /PRNewswire/
-- 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
We are on Twitter. Follow us
@DebiopharmNews at http://twitter.com/DebiopharmNews
Debiopharm Contact
Dawn
Bonine
Head of Communications
dawn.bonine@debiopharm.com
Tel: +41 (0)21 321 01 11
References
[1] 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
[2] 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
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