Debio 0123 in Combination With Carboplatin and Etoposide in Adult Participants With Small Cell Lung Cancer That Recurred or Progressed After Previous Standard Platinum-Based Therapy

NCT05815160 | Terminated Phase 1 FDA Drug

• 3 other identifiers: Debio 0123-SCLC-1042024-510980-40-00U1111-1302-8787
• Study Type: interventional
• Target: 34
• Locations: 2 countries
• Sites: 10

Brief Summary

The primary purpose of part 1 (dose escalation) of this study is to identify the recommended dose and to characterize the safety and tolerability of Debio 0123 in combination with carboplatin and etoposide. The primary purpose of part 2 (dose expansion) of this study is to characterize the safety and tolerability of Debio 0123 at the recommended dose when administered in combination with carboplatin and etoposide.

Conditions

Small Cell Lung Cancer Recurrent

Keywords

Small cell lung cancer (SCLC); Recurrent; Debio 0123; Carboplatin; Etoposide; WEE1 inhibitor; WEE-1 inhibitor; Platinum-based therapy; Platinum-based chemotherapy

Outcome Measures

Primary Outcomes (4)

• Part 1: Number of Participants Experiencing Dose-limiting Toxicities (DLTs)

  Cycle 1 (Cycle=21 days)

• Parts 1 and 2: Number of Participants With at Least One Treatment Emergent Adverse Event (TEAE)

  Approximately up to 44 months

• Parts 1 and 2: Number of Participants With Clinically Significant Abnormalities in Laboratory, Vital Signs, Electrocardiogram (ECG), and Echocardiogram Parameters

  Approximately up to 44 months

• Parts 1 and 2: Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS)

  Baseline up to approximately 44 months

Secondary Outcomes (19)

• Parts 1 and 2: Trough Concentration (Ctrough) of Debio 0123 and its Metabolite

  For Part 1: Predose from Day 2 to Day 11 of Cycle 1; For Part 2: Predose from Day 3 to Day 10 of Cycle 1 and only Day 8 of subsequent cycles up to Cycle 5 (Cycle=21 days)

• Parts 1 and 2: Maximum Plasma Concentration (Cmax) of Debio 0123 and its Metabolite

  For Part 1: Multiple timepoints post dose from Day 1 to Day 11 of Cycle 1 (Cycle=21 days); For Part 2: Will be derived from the population Pharmacokinetic (PK) model using the sparse samples collected

• Parts 1 and 2: Area Under the Concentration Curve Over 24 hours (AUC24h) of Debio 0123 and its Metabolite

  For Part 1: Multiple timepoints post dose from Day 1 to Day 11 of Cycle 1 (Cycle=21 days); For Part 2: Will be derived from the population PK model using the sparse samples collected

• Part 1: Time to Maximum Plasma Concentration (tmax) of Debio 0123 and its Metabolite

  Multiple timepoints post dose from Day 1 to Day 11 of Cycle 1 (Cycle=21 days)

• Part 1: Area Under the Concentration Curve up to the Last Measurable Concentration (AUClast) of Debio 0123 and its Metabolite

  Multiple timepoints post dose from Day 1 to Day 21 of Cycle 1 and Day 1 of Cycle 2 (Cycle=21 days)

Study Arms (2)

Part 1: Dose Escalation: Debio 0123 + Etoposide + Carboplatin

EXPERIMENTAL

Participants will receive Debio 0123 escalating doses, orally along with etoposide IV infusion and carboplatin IV infusion in 21-day cycles until disease progression or death or end of study.

Drug: Debio 0123; Drug: Etoposide; Drug: Carboplatin

Part 2: Dose Expansion: Debio 0123 + Etoposide + Carboplatin

EXPERIMENTAL

Participants will receive Debio 0123 recommended dose determined in Part 1 of the study, orally along with etoposide IV infusion and carboplatin IV infusion in 21-day cycles until disease progression or death or end of study.

Drug: Debio 0123; Drug: Etoposide; Drug: Carboplatin

Interventions

Debio 0123 DRUG

Administered as capsules.

Part 1: Dose Escalation: Debio 0123 + Etoposide + Carboplatin; Part 2: Dose Expansion: Debio 0123 + Etoposide + Carboplatin

Etoposide DRUG

Administered as IV infusion.

Part 1: Dose Escalation: Debio 0123 + Etoposide + Carboplatin; Part 2: Dose Expansion: Debio 0123 + Etoposide + Carboplatin

Carboplatin DRUG

Administered as IV infusion.

Part 1: Dose Escalation: Debio 0123 + Etoposide + Carboplatin; Part 2: Dose Expansion: Debio 0123 + Etoposide + Carboplatin

Eligibility Criteria

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

You may qualify if:

• Histologically or cytologically confirmed SCLC
• Tumor that is not bleeding
• Prior platinum-based chemotherapy (carboplatin and/or cisplatin)
• Part 1 (dose escalation): Recurrence or progression after a minimum of 45 days since the last dose of prior standard platinum-based therapy
• Part 2 (expansion): Recurrence or progression after a minimum of 90 days since the last dose of prior standard platinum-based therapy
• Measurable disease per RECIST 1.1
• Willingness and ability to undergo tumor biopsy unless an archived tumor sample is available
• ECOG performance status of 0-1
• Life expectancy of at least 3 months in the best judgment of the Investigator
• Adequate bone marrow, hepatic and renal function, adequate coagulation status
• Willingness and ability to comply with scheduled visits, study treatment plans, laboratory tests, and other study procedures.

You may not qualify if:

• Use of an investigational agent or medical device within 28 days prior to first dose of study treatment.
• History of other malignancies requiring active treatment in the last 2 years prior to first dose of study treatment, except for superficial bladder cancers, ductal carcinoma in situ or other carcinomas in situ, and non-melanoma skin cancers (basal cell/squamous cell skin cancer) that have been treated with curative intent.
• History of myocardial infarction or stroke in the last 6 months prior to first dose of study treatment, congestive heart failure greater than New York Heart Association (NYHA) class II, unstable angina pectoris, unexplained recurrent syncope, cardiac arrhythmia requiring treatment, known family history of sudden death from cardiac-related causes before the age of 50, or any cardiotoxicity experienced after previous chemotherapy.
• Left ventricular ejection fraction (LVEF) below 55%.
• QTcF \>450 ms, history of congenital long QT syndrome, or clinically significant conduction abnormality, or any conduction abnormality that may increase the risk of TdP.
• Clinically significant gastrointestinal abnormality that could affect the absorption of orally administered drugs
• Major surgery ≤4 weeks prior to first dose of study treatment or incomplete recovery from the surgical procedure at the time of the first dose of study treatment.
• Radiographic findings showing tumor involvement with large blood vessels or poor demarcation from them with increased risk for bleeding.
• Radiographic findings of Interstitial lung disease (ILD) that are considered clinically significant.
• Uncontrolled pleural effusion, pericardial effusion, or ascites requiring repeated drainage.
• Any infection requiring the systemic use of an antibiotic or antiviral agent.
• Known Hepatitis C virus (HCV), Hepatitis B virus (HBV), or Human Immunodeficiency Virus (HIV) infection. Participants with past infections that have been cured may be enrolled.
• Immunization with live or live-attenuated vaccine within 28 days prior to first dose of study treatment.
• Inability or unwillingness to swallow oral medications.
• Anticancer treatment (including chemotherapy), monoclonal antibodies/biologics, or radiotherapy with curative intent within 28 days prior to first dose of study treatment. Palliative radiation is allowed up to 1 week prior to study treatment start.

Sponsors & Collaborators

• Debiopharm International SA: lead

Study Sites (10)

Roswell Park Comprehensive Cancer Center

Buffalo, New York, 14263, United States

Location

Hospital Universitario de A Coruna

A Coruña, 15006, Spain

Location

Hospital Universitario Vall d'Hebron

Barcelona, 08035, Spain

Location

Institut Catala D'Oncologia - Badalona

Barcelona, 08908, Spain

Location

Clinica Universidad de Navarra

Madrid, 28027, Spain

Location

Hospital Universitario 12 de Octubre

Madrid, 28041, Spain

Location

Hospital Universitario HM Sanchinarro. START Madrid - Centro Integral Oncológico Clara Campal (CIOCC)

Madrid, 28050, Spain

Location

NEXT Oncology Madrid

Madrid, 28223, Spain

Location

Hospital Quironsalud Malaga

Málaga, 29004, Spain

Location

Hospital Clinico Universitario de Valencia

Valencia, 46010, Spain

Location

MeSH Terms

Conditions

Small Cell Lung Carcinoma; Recurrence

Interventions

Etoposide; Carboplatin

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Glucosides; Glycosides; Carbohydrates; Coordination Complexes

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: March 9, 2023
• First Posted: April 18, 2023
• Study Start: May 2, 2023
• Primary Completion: March 9, 2026
• Study Completion: March 9, 2026
• Last Updated: May 4, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1); ES (9)