Phase 1 study aimed at defining the dosage of Debio 0123 as monotherapy in adult patients with advanced solid tumors, followed by an expansion phase to evaluate safety and preliminary antitumor activity
Descrizione riassuntiva dello studio
This is a phase 1 study in which both the physician and the patient will know the dosage used of the investigational drug. Various hospitals will be involved in the study, which consists of 2 parts: • Part 1: dose escalation of Debio 0123 administered orally in repeated doses to determine the maximum tolerated dose and/or the recommended dose for phase 2 in patients with advanced solid tumors that have recurred or progressed after prior therapy and/or for whom no standard therapy with demonstrated benefit is available. Patients will receive Debio 0123 once daily at an initial dose of 30 mg. • Part 2: will begin once the maximum tolerated dose and/or the recommended dose for phase 2 has been determined and will involve the treatment of different tumors. This part will enroll patients who have progressed or have had a recurrence of 1 of the types of tumors specified below after standard therapy or for whom, in the opinion of the investigator, no effective standard therapy is available: - Arm A: uterine cancer - Arm B: ovarian, fallopian tube, and peritoneal cancer - Arm C: renal cell carcinoma, pancreatic cancer, or breast cancer. Patients with other types of solid tumors may be eligible upon documented agreement between Debiopharm and the investigator. During the study, a treatment cycle corresponds to 21 days, and tumor assessments must be performed until disease progression. For patients who discontinue study treatment, efficacy checks will include tumor assessments until disease progression or the start of a new antitumor treatment.
(BASEC)
Intervento studiato
The main interventions being examined are:
During the dose escalation in Part 1
• Determine the maximum tolerated dose and/or the recommended dose for phase 2 of Debio 0123 when administered to patients with advanced solid tumors that have recurred or progressed after prior therapy and/or for whom no standard therapy with demonstrated benefit is available.
During the expansion in Part 2
• Study the safety and tolerability of Debio 0123 in each arm and overall when administered at the recommended dose for phase 2 determined during the dose escalation phase (Part 1) of the study.
• Evaluate the antitumor activity of Debio 0123 when administered to patients in each arm.
(BASEC)
Malattie studiate
Debiopharm International SA is studying new treatments for locally advanced or metastatic solid tumors that have recurred or progressed following prior treatments and/or for which no cure is available. The goal is also to understand whether the investigational drug is effective, tolerated, and safe for use. The cell cycle is a process that our body controls through a sophisticated system. When the body's cells divide, the genetic material (DNA) is also duplicated, and it is very important that the repair of damaged DNA occurs before cell division. For this to happen, our body has a series of checks that are activated through certain specific molecules called proteins. Cells commonly use these proteins to have time to repair DNA damage in tumor cells, avoiding entering division with too much DNA damage. The drug under investigation, Debio 0123, prevents tumor cells from repairing their damaged DNA. In this way, it is believed that it may help kill tumor cells and reduce tumor size.
(BASEC)
Only dose escalation in Part 1 • Histologically or cytologically confirmed locally advanced or metastatic solid tumors. • Measurable or non-measurable disease according to RECIST version 1.1 criteria. • Disease progression during or after standard therapy and/or disease for which no standard therapy with proven benefit is available. Only expansion in Part 2 • Measurable disease according to RECIST version 1.1 criteria for each arm • Patients (≥18 years) who have progressed or have had a recurrence of one of the types of tumors specified in the study arms after standard therapy according to RECIST version 1.1, or for whom, in the opinion of the investigator, no effective standard therapy is available: • Arm A: - Histologically or cytologically confirmed serous uterine carcinoma (USC) that has recurred or progressed after at least 1 prior line of platinum-based therapy for the management of advanced or metastatic disease. Chemotherapy administered only in combination with primary RT as a radiosensitizer should not be considered as a systemic regimen. There is no restriction on the number of prior lines of therapy a patient may have received previously. Patients with microsatellite instability-high/mismatch repair deficiency (MSI-H/MMR-D) should have received prior PD1/PDL1 therapy or be ineligible for such therapy. • Arm B: - Histologically or cytologically confirmed epithelial ovarian cancer (EOC), recurrent, high-grade (serous, endometrioid, or clear cell), primary peritoneal cancer, or fallopian tube cancer. - Patients must have progressed after at least 1 prior platinum-based therapy for advanced/metastatic disease. Therapy with a poly(adenosine diphosphate [ADP]-ribose) polymerase (PARP) inhibitor is allowed. Patients may be platinum-resistant (defined as progression within 6 months of completing their most recent platinum-based chemotherapy regimen) or platinum-sensitive (defined as progression > 6 months after the end of their platinum-based chemotherapy). Platinum-based therapy should not be the last treatment before entering the study. Note: Patients with platinum-refractory disease (progression during platinum-containing therapy) are not eligible for Arm B of Part 2. • Arm C: - Histologically or cytologically confirmed renal carcinoma, breast cancer, or pancreatic cancer, locally advanced or metastatic. Dose escalation in Part 1 and expansion in Part 2 • Tumor accessible for biopsy and patient willing to undergo a tumor biopsy, unless an archival tumor sample is available. • Availability and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures. • Life expectancy of at least 3 months, in the investigator's best judgment. • Adequate bone marrow, liver, kidney function, and blood coagulation status. • Willingness to use highly effective contraceptive methods. (BASEC)
Criteri di esclusione
Dose escalation in Part 1 and expansion in Part 2 • Patients with active second malignant tumors that required therapy in the last 6 months, except for superficial bladder carcinomas, ductal carcinoma in situ, or other in situ carcinomas and non-melanoma skin carcinomas (basal cell/squamous cell carcinoma) that have been surgically treated. • Current use of an experimental agent or medical device. • Major surgical intervention ≤4 weeks prior to the first dose of study treatment or failure to recover from the surgical procedure. • Brain tumors and/or brain metastases unless asymptomatic, without the use of steroids for at least 28 days prior to the first dose of study treatment and not requiring active treatment in the last month prior to study entry. • History of myocardial infarction or stroke within the last 6 months, congestive heart failure, unstable angina pectoris, unexplained recurrent syncope, cardiac arrhythmia requiring treatment, family history of sudden death from cardiac causes, or any cardiotoxicity manifested after prior chemotherapy. • Left ventricular ejection fraction (LVEF) <55%. • History of congenital long QT syndrome or clinically significant conduction abnormalities, or any conduction abnormality that may increase the risk of torsades de pointes (TdP). • Concurrent use of a drug associated with a known risk of QTc interval prolongation. • Concurrent use of a drug or herbal product that is a CYP inhibitor or inducer, or strong CYP inhibitors, or any drug(s) on the list of prohibited medications (such as proton pump inhibitors, H2 receptor antagonists, etc.). • Known infection requiring systemic use of an antibiotic or antiviral agent. • Immunization with live or live attenuated vaccine within 28 days prior to study enrollment or scheduled injection of live or live attenuated vaccines. • Pregnancy or breastfeeding. • Inability or unwillingness to swallow oral medications. • Gastrointestinal abnormality that may affect drug absorption. • Chemotherapy, monoclonal/biological antibodies, or radiotherapy with curative intent within 28 days prior to the start of study treatment. Palliative radiotherapy for pain relief is allowed up to 1 week prior to starting study treatment. • Hypersensitivity to any of the excipients in the formulation of Debio 0123. • Unresolved adverse events or toxicity due to prior treatments, i.e., > Grade 1. Exceptions will be made for Grade 2 anemia (if hemoglobin is not less than 9 g/dL or 5.6 mmol/L) and for alopecia > Grade 2 and for endocrine disorders controlled by replacement therapy (e.g., hypothyroidism due to immune checkpoint inhibitors). • Unable to avoid exposure to high levels of ultraviolet (UV) radiation, e.g., occupational exposure to sunlight or sun exposure. • Previous exposure to any WEE1 inhibitor. (BASEC)
Luogo dello studio
Bellinzona, Berna, San Gallo
(BASEC)
Sponsor
Debiopharm International
(BASEC)
Contatto per ulteriori informazioni sullo studio
Persona di contatto in Svizzera
Orla Duffy-Roger
+41213210111
orla.duffyroger@clutterdebiopharm.comDebiopharm International
(BASEC)
Nome del comitato etico approvante (per studi multicentrici solo il comitato principale)
Commissione d'etica Ticino
(BASEC)
Data di approvazione del comitato etico
27.01.2022
(BASEC)
ID di studio ICTRP
NCT05109975 (ICTRP)
Titolo ufficiale (approvato dal comitato etico)
A Phase 1, dose-finding study of Debio 0123 as monotherapy in adult patients with advanced solid tumors, followed by an expansion part to assess safety and preliminary anti-tumor activity (BASEC)
Titolo accademico
A Phase 1, Dose-finding Study of Debio 0123 as Monotherapy in Adult Patients With Advanced Solid Tumors, Followed by an Expansion Part to Assess Safety and Preliminary Anti-tumor Activity (ICTRP)
Titolo pubblico
A Study to Evaluate Safety and Preliminary Anti-tumor Activity of Debio 0123 as Monotherapy in Adult Participants With Advanced Solid Tumors (ICTRP)
Malattie studiate
Advanced Solid Tumors (ICTRP)
Intervento studiato
Drug: Debio 0123 (ICTRP)
Tipo di studio
Interventional (ICTRP)
Disegno dello studio
Allocation: Non-Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: None (Open Label). (ICTRP)
Criteri di inclusione/esclusione
Inclusion Criteria:
- Part 1 dose escalation only:
- Histologically or cytologically confirmed locally advanced or metastatic solid
tumors.
- Measurable or non-measurable disease per Response Evaluation Criteria in Solid
Tumors (RECIST) version 1.1 criteria.
- Disease progression under or following standard therapy and/or disease for
which no available standard therapy of proven benefit.
- Part 2 expansion only:
- Measurable disease per RECIST version 1.1 criteria for each arm.
- Participants (=18 years old) who progressed or have recurrence of one of the
tumor types specified in the study arms following standard therapy according to
RECIST version 1.1, or for whom, in the opinion of the Investigator, no
effective standard therapy exists.
- Arm A: Histologically or cytologically confirmed USC that recurred or
progressed following at least 1 prior platinum-based line of therapy for
management of advanced or metastatic disease.
- Arm B: Histologically or cytologically confirmed, recurrent, high-grade EOC,
primary peritoneal cancer, or fallopian tube cancer with cyclin E1 driven
selection. Participants must have progressed after at least 1 prior
platinum-based therapy for advanced/metastatic disease.
- Arm C: Histologically or cytologically confirmed, locally advanced or
metastatic solid tumor with biomarker-driven selection.
- Part 1 dose escalation and Part 2 expansion:
- Accessible tumor for biopsy, and participant willing to undergo tumor biopsy
unless archived tumor sample is available.
- Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1.
- Life expectancy of at least 3 months, in the best judgment of the Investigator.
- Adequate bone marrow, liver biochemistry, renal function, and coagulation
status.
- Willing to practice highly effective methods of contraception.
- Willingness and ability to comply with scheduled visits, treatment plans,
laboratory tests, and other study procedures.
Exclusion Criteria:
- Participants with active second malignancies requiring therapy in the last 6 months,
with the exception of superficial bladder cancers, ductal carcinoma in situ or other
carcinomas in situ, and non-melanoma non-melanoma skin cancers (basal cell/squamous
cell skin cancer) that have been treated surgically.
- Current use of an investigational agent or a medical device.
- Major surgery =4 weeks prior to the first dose of study treatment or who have not
recovered from the surgical procedure.
- Brain tumors and/or brain metastases unless they are asymptomatic, stable on recent
imaging (not dated more than 28 days from the inclusion date), and have not required
active treatment in the last month before study entry.
- History of myocardial infarction or stroke within 6 months, congestive heart failure
greater than New York Heart Association (NYHA) class II, unstable angina pectoris,
unexplained recurrent syncope, cardiac arrhythmia requiring treatment, family
history of sudden death from cardiac-related causes before the age of 50, or any
cardiotoxicity experienced after previous chemotherapy.
- Known infection requiring systemic use of an antibiotic or antiviral agent.
- Immunization with live or live-attenuated vaccine within 28 days prior to study
inclusion or planned injection of live or live-attenuated vaccines.
- Pregnancy or breast-feeding.
- Inability or unwillingness to swallow oral medication.
- Clinically significant gastrointestinal abnormality that would affect the absorption
of the drug.
- Any anti-cancer treatment, monoclonal antibodies/biologics, investigational
treatment, or radiotherapy with curative intent within 28 days prior to starting
study treatment. Palliative radiation for pain relief is allowed up to 1 week prior
to starting study treatment.
- Unresolved AEs or toxicities due to previous treatments, i.e., >Grade 1. Exceptions
will be made for Grade 2 anemia (if hemoglobin is not less than 9 g/dL or 5.6
mmol/L) and >Grade 2 alopecia and endocrinopathies controlled by replacement therapy
(example, hypothyroidism due to immune checkpoint inhibitors).
[Note: Other inclusion/exclusion criteria mentioned in the protocol may apply.] (ICTRP)
non disponibile
Endpoint primari e secondari
Part 1: Maximum Tolerated Dose (MTD) as Determined by Percentage of Participants with Dose Limiting Toxicities (DLTs);Part 1: Recommended Phase 2 Dose (RP2D) as Determined by Percentage of Participants with DLTs and Cumulative Safety Data;Part 2: Percentage of Participants with Serious Adverse Events (SAEs);Part 2: Percentage of Participants with Treatment-Emergent Adverse Events (TEAEs) and Laboratory Abnormalities;Part 2: Percentage of Participants with Treatment Discontinuations and Treatment Modifications due to Adverse Events (AEs) and Laboratory Abnormalities;Part 2: Overall Response Rate (ORR) (ICTRP)
Part 1: Percentage of Participants with SAEs;Part 1: Percentage of Participants with TEAEs and Laboratory Abnormalities;Part 1: Plasma Concentration of Debio 0123;Parts 1 and 2: Anti-Tumor Activity as Assessed by Percentage of Participants with Tumor Response (ICTRP)
Data di registrazione
26.10.2021 (ICTRP)
Inclusione del primo partecipante
non disponibile
Sponsor secondari
non disponibile
Contatti aggiuntivi
Debiopharm International S.A, clinicaltrials@debiopharm.com, +41 21 321 01 11 (ICTRP)
ID secondari
2023-504824-24, Debio 0123-102 (ICTRP)
Risultati-Dati individuali dei partecipanti
non disponibile
Ulteriori informazioni sullo studio
https://clinicaltrials.gov/ct2/show/NCT05109975 (ICTRP)
Risultati dello studio
Riepilogo dei risultati
non disponibile
Link ai risultati nel registro primario
non disponibile