Study of pembrolizumab, lenvatinib and chemotherapy combination in first line lung cancer

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Fundacion GECP

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

7 Nov 2022 → ongoing

Decision date (initial)

2024-03-19

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Fundación GECP

External identifiers

EU CT number

2024-511412-25-00

EudraCT number

2020-005230-15

ClinicalTrials.gov

NCT05384015

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Efficacy, Safety

Safety run-in (part 1): To evaluate the safety and tolerability for lenvatinib 8 mg to be used in combination with pembrolizumab plus chemotherapy (carboplatin + etoposide).
Treatment (part 2): To evaluate progression free survival (PFS) of lenvatinib 20mg in addition to the rest of the compounds as assessed by investigator according to RECIST 1.1.

Secondary objectives 2

1. Safety run-in (part 1): To determine the preliminary efficacy of the combination.
2. Treatment (part 2): To evaluate the safety and tolerability of the combination.

Conditions and MedDRA coding

First line treatment for extensive-stage small cell lung cancer small cell lung cancer patients (ES-SCLC)

Regulatory references

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 11

1. Histologically or cytologically documented new diagnosis of SCLC by histology or cytology from brushing, washing, or needle aspiration.
2. Have voluntarily agreed to participate by giving written consent for the study prior to any specific protocol procedures.
3. Have adequate organ function.
4. ES-SCLC, stage IV disease by the American Joint Committee on Cancer, 8th Edition criteria, [T any, N any, M1a, M1b, M1c], or T3–4 due to multiple lung nodules that are too extensive or tumor/nodal volume that is too large to be encompassed in a tolerable radiation plan.
5. Have at least one lesion that meets criteria for being measurable, as defined by RECIST 1.1.
6. Have provided archival tumor tissue sample or newly obtained core or excisional biopsy of a tumor lesion not previously irradiated for biomarker assessment.
7. Be male or female ≥18 years of age inclusive, on the day of signing informed consent.
8. Have a life expectancy of at least 3 months from the study start.
9. Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 within 7 days prior to the first dose of study intervention
10. Male participants are eligible to participate if they agree to the following during the intervention period and for at least 30 days after the last dose of lenvatinib placebo and up to 180 days after the last dose of chemotherapeutic agents: -Refrain from donating sperm PLUS either: -Be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis) and agree to remain abstinent OR -Must agree to use contraception unless confirmed to be azoospermic (vasectomized or secondary to medical cause ) as detailed below: # Agree to use a male condom plus partner use of an additional contraceptive method when having penile-vaginal intercourse with a WOCBP who is not currently pregnant.
11. A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies: o Is not a WOCBP OR - Is a WOCBP and using a contraceptive method that is highly effective (with a failure rate of <1% per year), with low user dependency, or be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis), during the intervention period and for at least 120 days post pembrolizumab and 30 days post-lenvatinib and up to 180 days post last dose of chemotherapeutic agents, whichever occurs last. The investigator should evaluate the potential for contraceptive method failure in relationship to the first dose of study intervention. - A WOCBP must have a negative highly sensitive pregnancy test within 24 hours before the first dose of study intervention. - If a urine test cannot be confirmed as negative , a serum pregnancy test is required. In such cases, the participant must be excluded from participation if the serum pregnancy result is positive.

Exclusion criteria 36

1. Has received any prior therapy for the treatment of SCLC.
2. Is expected to require any other form of antineoplastic therapy for SCLC, including radiation therapy while on study.
3. Active CNS metastases and/or carcinomatous meningitis as determined per CT or MRI during screening. Participants with previously treated brain metastases may participate only if they satisfy the following: # Completed treatment at least 14 days prior to the first dose of study (FDS). # Are clinically and radiologically stable # Patients with new asymptomatic CNS metastases detected at the screening scan must receive radiation therapy and/or surgery for CNS metastases. Following treatment, these patients may then be eligible without the need for an additional brain scan prior to enrollment, if all other criteria are met.
4. Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor
5. Spinal cord compression not definitively treated with surgery and/or radiation or previously diagnosed and treated spinal cord compression without evidence that disease has been clinically stable for ≥ 1 week prior to enrollment.
6. Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures
7. Has known history of, or active, neurologic paraneoplastic syndrome of autoimmune nature
8. Radiographic evidence of intratumoral cavitations, encasement, or invasion of a major blood vessel.
9. Has had major surgery within 4 weeks prior to FDS.
10. Has received a live vaccine or live-attenuated vaccine within 30 days prior to FDS.
11. Is currently participating inor has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to FDS.
12. Has an active autoimmune disease or inflammatory disorder that has required systemic treatment in the past 2 years.
13. Has a diagnosis of immunodeficiency or is taking chronic systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to FDS.
14. Has known history of a second malignancy other than SCLC, unless potentially curative treatment has been completed with no evidence of malignancy for at least 3 years since the initiation of that therapy.
15. Poor controlled hypertension despite appropriate treatment.
16. Participants with proteinuria >1+ on urine dipstick testing/urinalysis will undergo 24-hour urine collection for quantitative assessment of proteinuria. Participants with urine protein ≥1 g/24 hours will be ineligible.
17. Has a prolongation of QTc interval of >480 msec.
18. Has a known history of interstitial lung disease, idiopathic pulmonary fibrosis, organizing pneumonia , drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan
19. Uncontrolled intercurrent active infection at the time of enrollment requiring systemic therapy.
20. Has a known history of HIV infection.
21. Has a known history of Hepatitis B or active Hepatitis C virus infection
22. Has a known history of active tuberculosis.
23. Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study.
24. Has known psychiatric or substance abuse disorders.
25. Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of trial treatment.
26. Prior allogeneic bone marrow transplantation or solid organ transplant.
27. Any gastrointestinal condition that would affect the absorption of Lenvatinib
28. Has active hemoptysis or major arterial thromboembolic event within 2 weeks prior to the first dose of study intervention.
29. Has significant cardiovascular impairment within 12 months prior to the first dose of study intervention, including history of congestive heart failure greater than NYHA Class II, unstable angina, myocardial infarction, CVA, or cardiac arrhythmia associated with hemodynamic instability.
30. Has a history of a severe hypersensitivity reaction to treatment with another monoclonal Ab or has a known hypersensitivity to lenvatinib, pembrolizumab, carboplatin or etoposide and/or any of its excipients.
31. Has a clinically active diverticulitis, inflammatory bowel disease, intra-abdominal abscess, gastrointestinal obstruction and/or abdominal carcinomatosis.
32. Has a history of a gastrointestinal perforation within 6 months before FDS.
33. Has preexisting Grade ≥ 3 gastrointestinal or non-gastrointestinal fistula.
34. Has serious nonhealing wound, ulcer, or bone fracture within 28 days before FDS.
35. Has any major hemorrhage or venous thromboembolic events within 3 months before FDS.
36. Poor medical risk due to a serious, uncontrolled medical disorder or nonmalignant systemic disease.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Part 1: * Safety and tolerability Dose-limiting toxicities (DLTs), adverse events (AEs) and study intervention discontinuations due to AEs. Part 2: • Progression-free Survival (PFS) per RECIST 1.1 assessed by investigator
2. Part 2: • Progression-free Survival (PFS) per RECIST 1.1 assessed by investigator

Secondary endpoints 7

1. Part 1 (for patients treated at part 2): Objective response per RECIST 1.1 based on investigator
2. Part 1 (for patients treated at part 2): Duration of response (DOR) per RECIST 1.1 based on investigator
3. Part 1 (for patients treated at part 2): Overall Survival
4. Part 2: Objective response per RECIST 1.1 based on investigator
5. Part 2: DOR per RECIST 1.1 based on investigator
6. Part 2: Safety and tolerability
7. Part 2: Overall Survival

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Fundacion GECP

Sponsor organisation

Fundacion GECP

Address

Avinguda Meridiana 358 6 Planta

City

Barcelona

Postcode

08027

Country

Spain

Scientific contact point

Organisation

Fundacion GECP

Contact name

Mariano Provencio

Public contact point

Organisation

Fundacion GECP

Contact name

Maria Fernández

Locations

1 EU/EEA country · 18 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 14 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

7 submissions — initial application plus substantial / non-substantial modifications