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

Debiopharm

Status and phase: Active, not recruiting; Phase 1

Conditions: Small Cell Lung Cancer Recurrent

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

Study type: Interventional

Funder types: Industry

Identifiers

NCT05815160

U1111-1302-8787 (Other Identifier)

2024-510980-40-00 (EU Trial (CTIS) Number)

Debio 0123-SCLC-104

Details and patient eligibility

About

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.

Enrollment: 34 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Histologically or cytologically confirmed SCLC

2. Tumor that is not bleeding

3. 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

4. Measurable disease per RECIST 1.1

5. Willingness and ability to undergo tumor biopsy unless an archived tumor sample is available

6. ECOG performance status of 0-1

7. Life expectancy of at least 3 months in the best judgment of the Investigator

8. Adequate bone marrow, hepatic and renal function, adequate coagulation status

9. Willingness and ability to comply with scheduled visits, study treatment plans, laboratory tests, and other study procedures.

Exclusion criteria

1. Use of an investigational agent or medical device within 28 days prior to first dose of study treatment.
2. 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.
3. 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.
4. Left ventricular ejection fraction (LVEF) below 55%.
5. 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.
6. Clinically significant gastrointestinal abnormality that could affect the absorption of orally administered drugs
7. 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.
8. Radiographic findings showing tumor involvement with large blood vessels or poor demarcation from them with increased risk for bleeding.
9. Radiographic findings of Interstitial lung disease (ILD) that are considered clinically significant.
10. Uncontrolled pleural effusion, pericardial effusion, or ascites requiring repeated drainage.
11. Any infection requiring the systemic use of an antibiotic or antiviral agent.
12. 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.
13. Immunization with live or live-attenuated vaccine within 28 days prior to first dose of study treatment.
14. Inability or unwillingness to swallow oral medications.
15. 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.
16. Unresolved AEs or toxicities due to previous treatments >Grade 1. Note: Participants with ≤Grade 2 alopecia or endocrinopathies controlled by replacement therapy are exceptions and may qualify for the study.
17. Hypersensitivity to Debio 0123, etoposide or carboplatin, or any of the excipients found in the formulations for Debio 0123, etoposide, or carboplatin. If a prior hypersensitivity to carboplatin has been observed but a successful desensitization was performed for the participant, he or she may be eligible for the study.
18. Prior exposure to any WEE1 inhibitor

Note: Other inclusion/exclusion criteria mentioned in the protocol may apply.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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34 participants in 2 patient groups

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

Experimental group

Description:

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.

Treatment:

Drug: Carboplatin

Drug: Etoposide

Drug: Debio 0123

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

Experimental group

Description:

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.

Treatment:

Drug: Carboplatin

Drug: Etoposide

Drug: Debio 0123