Study of Oral Debio 0123 in Combination With Carboplatin in Participants With Advanced Solid Tumors

NCT03968653 | Terminated Phase 1

• 3 other identifiers: Debio 0123-1012024-510984-52U1111-1302-8405
• Study Type: interventional
• Target: 76
• Locations: 2 countries
• Sites: 8

Brief Summary

This study has two parts: Dose Escalation and Dose Expansion. The primary objective of the study, in the Dose Escalation Part is to determine the recommended phase 2 dose (RP2D) of Debio 0123 when administered in combination with carboplatin in participants with advanced solid tumors that recurred or progressed after prior cisplatin or carboplatin containing therapy and for which no standard therapy of proven benefit is available. The primary objective of the study, in the Dose Expansion Part is to characterize the safety and tolerability of Debio 0123 when administered in combination with carboplatin at the RP2D determined during the dose escalation part of the study and to evaluate the preliminary antitumor activity of Debio 0123 when administered in combination with carboplatin.

Conditions

Advanced Solid Tumors

Keywords

WEE1-inhibitor

Outcome Measures

Primary Outcomes (4)

• Dose Escalation: Recommended Phase 2 Dose (RP2D) of Debio 0123 When Administered in Combination with Carboplatin

  2 Cycles i.e., 45 days (Cycle 1 = 24 days; Cycle 2 onwards = 21 day-cycles)

• Dose Expansion: Percentage of Participants with Treatment-Emergent Serious Adverse Events (SAEs)

  Up to 46 months

• Dose Expansion: Percentage of Participants with Treatment Discontinuations and Treatment Modifications Due to Adverse Events (AEs) and Laboratory Abnormalities

  Up to 46 months

• Dose Expansion: Overall Response Rate (ORR)

  From the start of study treatment until disease progression/recurrence is documented or analysis cut-off, whichever occurs first (up to 46 months)

Secondary Outcomes (22)

• Dose Escalation: Percentage of Participants with Dose Limiting Toxicities (DLTs) of Debio 0123 When Administered in Combination with Carboplatin

  2 Cycles i.e., 45 days (Cycle 1 = 24 days; Cycle 2 onwards = 21 day-cycles)

• Dose Escalation: Percentage of Participants with Treatment-Emergent SAEs

  Up to 46 months

• Dose Escalation: Percentage of Participants with TEAEs and Laboratory Abnormalities

  Up to 46 months

• Dose Escalation: Percentage of Participants with Treatment Discontinuations and Treatment Modifications Due to Adverse Events (AEs) and Laboratory Abnormalities

  Up to 46 months

• Dose Escalation: Number of Participants with Changes in Vital Signs

  Day 1 of each cycle (up to 46 months) [Group A: Cycle 1 = 24 days, Cycle 2 onwards and all cycles in Group B = 21-day cycles]

Study Arms (3)

Dose Escalation: Group A: Debio 0123

EXPERIMENTAL

Participants will receive Debio 0123 as monotherapy (Day -3), orally, daily for 3 days during Cycle 1 then in combination with carboplatin intravenous infusion from Cycle 2 onwards. Depending on pharmacokinetics (PK) and safety results from previous cohorts, the Debio 0123 dosing regimen may be modified for subsequent cohorts.

Drug: Debio 0123; Drug: Carboplatin

Dose Escalation: Group B: Debio 0123

EXPERIMENTAL

Participants will receive Debio 0123, orally, daily, for 6 days during each cycle in combination with carboplatin IV infusion.

Drug: Debio 0123; Drug: Carboplatin

Dose Expansion: Debio 0123

EXPERIMENTAL

Participants with platinum-resistant selected solid tumors will receive Debio 0123, orally, daily, depending on the RP2D determined in the previous part, for 3 or 6 days during each cycle in combination with carboplatin IV infusion.

Drug: Debio 0123; Drug: Carboplatin

Interventions

Debio 0123 DRUG

Debio 0123 will be given as an oral capsule for 3 days during each 21-day cycle, except Cycle 1 which is of 24 days.

Dose Escalation: Group A: Debio 0123

Carboplatin DRUG

Carboplatin will be given as an IV infusion in combination with Debio 0123 on Day 1 from Cycle 2 onwards in Group A.

Dose Escalation: Group A: Debio 0123

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Dose Escalation:
• Histologically or cytologically confirmed locally advanced or metastatic solid and nonbleeding tumors that had recurred or progressed following standard therapy, has not responded to standard therapy or for which no standard therapy of proven benefit is available
• Able and willing to undergo tumor biopsy
• Prior platinum-based therapy (carboplatin or cisplatin).
• Life expectancy of at least 3 months
• ECOG PS 0-1
• Dose Expansion:
• Histologically or cytologically confirmed, recurrent solid tumors of selected types.
• Participants must have progressed after at least 1 prior platinum-based line of therapy for advanced/metastatic disease.
• Participants must be platinum resistant (defined as progression within 6 months of completion of their most recent platinum-based chemotherapy). Prior poly (ADP-ribose) polymerase (PARP) inhibitor therapy is allowed. Platinum-based therapy does not need to be the last treatment prior to study entry.
• Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
• Documented progressive or recurrent disease according to RECIST 1.1 since the last anti-cancer therapy and prior to study entry
• Able and willing to undergo tumor biopsy
• ECOG PS 0-1
• Life expectancy of at least 3 months

You may not qualify if:

• Dose Escalation and Dose Expansion:
• History of other malignancies requiring active treatment in the last 6 months
• Brain tumors and/or symptomatic brain metastases
• Receiving other investigating agents
• Presence of significant cardiovascular disease or other co-morbidities such as symptomatic ascites
• Prior exposure to any WEE1 inhibitor

Sponsors & Collaborators

• Debiopharm International SA: lead

Study Sites (8)

University Medical Center Groningen

Groningen, 9713, Netherlands

Location

Leiden University Medical Center, Dept. of Clinical Oncology

Leiden, 2333, Netherlands

Location

Radboud university medical center

Nijmegen, 6525, Netherlands

Location

Hospital Vall Hebrón, Unidad de Investigación en Terapia Molecular (UITM)

Barcelona, 08035, Spain

Location

Clinica Universidad de Navarra

Madrid, 28027, Spain

Location

Hospital Universitario Virgen de la Victoria

Málaga, 29010, Spain

Location

Clinica Universidad de Navarra - Pamplona

Pamplona, 31008, Spain

Location

Instituto Valenciano de Oncologia

Valencia, 46009, Spain

Location

MeSH Terms

Interventions

Carboplatin

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 28, 2019
• First Posted: May 30, 2019
• Study Start: July 30, 2019
• Primary Completion: October 23, 2025
• Study Completion: October 23, 2025
• Last Updated: December 5, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

NL (3); ES (5)