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

Debiopharm

Status and phase: Terminated; Phase 1

Conditions: Advanced Solid Tumors

Treatments: Drug: Carboplatin; Drug: Debio 0123

Study type: Interventional

Funder types: Industry

Identifiers

NCT03968653

U1111-1302-8405 (Other Identifier)

Debio 0123-101

2024-510984-52 (Other Identifier)

Details and patient eligibility

About

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.

Enrollment: 76 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

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

Exclusion criteria

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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76 participants in 3 patient groups

Dose Escalation: Group A: Debio 0123

Experimental group

Description:

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.

Treatment:

Drug: Debio 0123

Drug: Carboplatin

Drug: Debio 0123

Drug: Carboplatin

Dose Escalation: Group B: Debio 0123

Experimental group

Description:

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

Treatment:

Drug: Debio 0123

Drug: Carboplatin

Drug: Debio 0123

Drug: Carboplatin

Dose Expansion: Debio 0123

Experimental group

Description:

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.

Treatment:

Drug: Debio 0123

Drug: Carboplatin

Drug: Debio 0123

Drug: Carboplatin