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

Small Cell Lung Cancer Recurrent Clinical Trial

Official title:

A Phase 1 Dose-Escalation and Expansion Study to Assess Safety and Preliminary Antitumor Activity of 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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05815160
• Other study ID #: Debio 0123-SCLC-104
• Secondary ID: 2022-001976-32
• Status: Recruiting
• Phase: Phase 1
• Start date: May 2, 2023
• Est. completion date: April 2026

Study information

• Verified date: January 2024
• Source: Debiopharm International SA
• Contact: Debiopharm International S.A
• Phone: +41 21 321 01 11
• Email: clinicaltrials[@]debiopharm.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The primary purpose of part 1 (dose escalation) of this study is to identify the recommended phase 2 dose (RP2D) 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 RP2D when administered in combination with carboplatin and etoposide.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 54
• Est. completion date: April 2026
• Est. primary completion date: January 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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. 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.

Related Conditions & MeSH terms

• Lung Neoplasms
• Small Cell Lung Cancer Recurrent
• Small Cell Lung Carcinoma

Intervention

Drug:
• Debio 0123
Administered as capsules.
• Etoposide
Administered as IV infusion.
• Carboplatin
Administered as IV infusion.

Locations

Country	Name	City	State
Spain	Hospital Universitario Vall d'Hebron	Barcelona
Spain	Clinica Universidad de Navarra	Madrid
Spain	Hospital Universitario 12 de Octubre	Madrid
Spain	Hospital Universitario HM Sanchinarro. START Madrid - Centro Integral Oncológico Clara Campal (CIOCC)	Madrid
Spain	Clinica Universidad de Navarra	Pamplona
Spain	Hospital Clinico Universitario de Valencia	Valencia
United States	Roswell Park Comprehensive Cancer Center	Buffalo	New York
United States	Henry Ford Health System	Detroit	Michigan
United States	University of Arkansas for Medical Sciences	Little Rock	Arkansas

Sponsors (1)

Lead Sponsor	Collaborator
Debiopharm International SA

Countries where clinical trial is conducted

United States,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Part 1: Number of Participants Experiencing Dose-limiting Toxicities (DLTs)		Cycle 1 (Cycle=21 days)
Primary	Parts 1 and 2: Number of Participants With at Least One Treatment Emergent Adverse Event (TEAE)		Approximately up to 44 months
Primary	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
Primary	Parts 1 and 2: Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS)		Baseline up to approximately 44 months
Secondary	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 (Cycle=21 days)
Secondary	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
Secondary	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
Secondary	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)
Secondary	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)
Secondary	Part 1: Area Under the Concentration Curve up to Infinity (AUCinf) 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)
Secondary	Part 1: Apparent Terminal Half-life (t1/2) 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)
Secondary	Part 1: Apparent Clearance (CL/F) of Debio 0123		Multiple timepoints post dose from Day 1 to Day 21 of Cycle 1 and Day 1 of Cycle 2 (Cycle=21 days)
Secondary	Part 1: Apparent Volume of Distribution (Vd/F) of Debio 0123		Multiple timepoints post dose from Day 1 to Day 21 of Cycle 1 and Day 1 of Cycle 2 (Cycle=21 days)
Secondary	Part 1: Maximum Plasma Concentration (Cmax) of Etoposide		Multiple timepoints from administration to post dose from Day 1 to Day 3 of Cycle 1 (Cycle=21 days)]
Secondary	Part 1: Area Under the Concentration Curve Over 24 hours (AUC24h) of Etoposide		Multiple timepoints post dose from Day 1 to Day 5 of Cycle 1 (Cycle=21 days)
Secondary	Part 1: Trough Concentration (Ctrough) of Etoposide		Predose from Day 2 to Day 5 of Cycle 1 (Cycle=21 days)
Secondary	Part 1: Maximum Plasma Concentration (Cmax) of Carboplatin		Multiple timepoints from administration up to 6 hours post dose on Day 1 of Cycle 1 (Cycle=21 days)
Secondary	Parts 1 and 2: Percentage of Participants With Best Overall Response (BOR) Assessed as per Response Evaluation Criteria in Solid Tumours (RECIST) 1.1 Criteria		From the start of study treatment until disease progression or end of study (up to approximately 44 months)
Secondary	Parts 1 and 2: Percentage of Participants With Objective Response (OR) Assessed as per RECIST 1.1 Criteria		Up to end of study (approximately 44 months)
Secondary	Parts 1 and 2: Percentage of Participants With Disease Control (DC) Assessed as per RECIST 1.1 Criteria		From the start of study treatment until disease progression or end of study (up to approximately 44 months)
Secondary	Parts 1 and 2: Duration of Response (DOR) Assessed as per RECIST 1.1 Criteria		Up to disease progression or end of study (approximately 44 months)
Secondary	Parts 1 and 2: Progression Free Survival (PFS) Assessed as per RECIST 1.1 Criteria		From the start of study treatment until disease progression or death or end of study (up to approximately 44 months)
Secondary	Part 2: Overall Survival		From the start of study treatment until death from any cause or end of study (up to approximately 44 months