Study of Pembrolizumab, Lenvatinib and Chemotherapy Combination in First Line Extensive-stage Small Cell Lung Cancer

NCT05384015 | Active Not Recruiting Phase 2

• 2 other identifiers: GECP 20/06_PEERS2020-005230-15
• Study Type: interventional
• Target: 46
• Locations: 1 country
• Sites: 18

Brief Summary

This is a multicenter, open-label, non-randomized, single arm, 2 parts, phase II clinical trial evaluating the efficacy and safety of pembrolizumab and lenvatinib plus standard of care chemotherapy (with carboplatin and etoposide ) in subjects with histologically confirmed extensive-stage small-cell lung cancer who have not previously received systemic therapy for this malignancy.

Conditions

Small Cell Lung Cancer Extensive Stage

Keywords

Lenvatinib; Pembrolizumab; Lung cancer

Outcome Measures

Primary Outcomes (2)

• Part 1: Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability) of lenvatinib 8 mg to be used in combination with pembrolizumab plus chemotherapy

  Occurrence and severity of adverse events, with severity determined by NCI CTCAE v5.0 criteria.

  From the subject's written consent to participate in the study through 90 days after the final administration of the drug

• Part 2:To assess the efficacy of the treatment in terms of the Progression Free Survival (PFS)

  PFS is defined as the time from enrollment to the date of the first documentation of disease progression, as determined by investigator per RECIST 1.1, or death from any cause, whichever is earlier.

  From the date of the end of induction treatment until 12 months

Secondary Outcomes (7)

• Part 1 (for patients treated at part 2): Objective response per RECIST 1.1 based on investigator

  From the date of the end of treatment until 12 months

• Part 1 (for patients treated at part 2): Duration of Response (DOR) per RECIST 1.1 based on investigator

  From date of documentation of tumor response until date of first documented progression, assessed up to 12 months

• Part 1 (for patients treated at part 2): Overall Survival

  From the date of the end of treatment until 12 months

• Part 2: Objective response per RECIST 1.1 based on investigator

  From the date of the end of treatment until 12 months

• Part 2: Duration of Response (DOR) per RECIST 1.1 based on investigator

  From date of documentation of tumor response until date of first documented progression, assessed up to 12 months

Study Arms (1)

Experimental

EXPERIMENTAL

Trial Treatment administration: at induction phase cycles will be administered every 3 weeks. For carboplatin (AUC5) and etoposide (100mg/m2) the maximum dose exposure will be 4 cycles or until reaching a discontinuation criterion. At this induction phase lenvatinib (8mg) will be orally administered daily and pembrolizumab (200mg) IV every 3 weeks. At maintenance phase lenvatinib will be administered at 20 mg dose and pembrolizumab at the same dose (200mg) until study intervention completion (total of 35 cycles of pembrolizumab/no treatment duration limit for lenvatinib) or reaching a discontinuation criterion.

Drug: Lenvatinib; Drug: Pembrolizumab; Drug: Etoposide; Drug: Carboplatin

Interventions

Lenvatinib DRUG

Lenvatinib is an oral, potent multiple receptor tyrosine kinase (RTK) i that selectively inhibits VEGF-driven VEGFR2 phosphorylation and suppressed proliferation and tube formation in human umbilical vein endothelial cell models. Antitumor activity of lenvatinib in vivo has been shown in numerous xenograft animals. These results suggest that lenvatinib may be a novel anticancer therapy through inhibition of angiogenesis and may be useful as either monotherapy or in combination with other anticancer drugs. Part 1 (safety run-in) and Part 2: The study intervention consists of: Dose: 8 mg (induction) and 20 mg (maintenance) Dose Frequency: Once daily Dose formulation: Capsule Route of administration: Oral Treatment duration: 4 cycles (induction) and no treatment duration limit (maintenance).

Also known as: LENVIMA, KISPLYX

Experimental

Pembrolizumab DRUG

Pembrolizumab is a potent humanized immunoglobulin G4 (IgG4) monoclonal antibody (mAb) with high specificity of binding to the programmed cell death 1 (PD-1) receptor, thus inhibiting its interaction with programmed cell death ligand 1 (PD-L1) and programmed cell death ligand 2 (PD-L2). Part 1 (safety run-in) and Part 2: Dose: 200 mg Frequency: Day 1, Q3W Route: Intravenous Treatment Period: Up to 35 cycles or until reaching a discontinuation criterion

Also known as: KEYTRUDA

Experimental

Etoposide DRUG

Standard first-line treatment for the vast majority of patients with SCLC, regardless of stage, involves combination chemotherapy with etoposide plus cisplatin or carboplatin. Pharmacotherapeutic group: Cytostatics, plant alkaloids and other natural products, derived from podophyllotoxin. Mechanism of action :The main effect of etoposide appears to be in the late S and early G2 phase of the cell cycle, in mammalian cells. Part 1 (safety run-in) and Part 2: Dose: 100 mg/m2 Frequency: Day 1-3, Q3W Route: Intravenous Treatment Period: 4 cycles

Also known as: Etoposide Tevagen

Experimental

Carboplatin DRUG

Pharmacotherapeutic group: Other antineoplastic agents, platinum compounds. Carboplatin, like cisplatin, binds to DNA to produce inter- and intra-strand cross-links cells exposed to carboplatin. DNA reactivity has been linked to cytotoxicity. Part 1 (safety run-in) and Part 2: Dose: AUC5 Frequency: Day 1, Q3W Route: Intravenous Treatment Period: 4 cycles

Also known as: Carboplatin Accord

Experimental

Eligibility Criteria

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

You may qualify if:

• \- 1. Histologically or cytologically documented new diagnosis of SCLC by histology or cytology from brushing, washing, or needle aspiration.
• Note: Subjects who do not have histology samples (defined as core or excisional biopsy, or resections) will need to undergo a new biopsy to provide a tissue sample. Mixed tumors are not eligible.
• \. ES-SCLC, stage IV disease by the American Joint Committee on Cancer, 8th Edition criteria (70), \[T any, N any, M1a, M1b, M1c\], 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.
• \. Have at least one lesion that meets criteria for being measurable, as defined by RECIST 1.1.
• \. Have provided archival tumor tissue sample or newly obtained core or excisional biopsy of a tumor lesion not previously irradiated for biomarker assessment.
• \. Be male or female ≥18 years of age inclusive, on the day of signing informed consent.
• \. Have a life expectancy of at least 3 months from the study start.
• \. Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 within 7 days prior to the first dose of study intervention.
• \. 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.
• \- 9. A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies:
• Is not a WOCBP OR

You may not qualify if:

• \. Has received any prior therapy (chemotherapy, radiotherapy, surgical resection) or other investigational agent for the treatment of SCLC.
• \. Is expected to require any other form of antineoplastic therapy for SCLC, including radiation therapy while on study.
• \. Active CNS metastases and/or carcinomatous meningitis as determined per CT or MRI during screening. Participants with previously treated brain metastases (eg, whole brain radiation treatment \[WBRT\], stereotactic radiosurgery, or equivalent) may participate only if they satisfy the following:
• Completed treatment at least 14 days prior to the first dose of study intervention.
• Are clinically stable, without requirement of steroid treatment for at least 7 days prior to first dose of study intervention.
• Are 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.
• \. 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 (eg, CTLA-4, OX-40, CD137).
• \. 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.
• \. Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently). A subject who is clinically stable following treatment for these conditions (including therapeutic thoraco- or paracentesis) is eligible.
• \. .Has known history of, or active, neurologic paraneoplastic syndrome of autoimmune nature.
• \. Has had major surgery within 4 weeks prior to first dose of study interventions.
• \. Has received a live vaccine or live-attenuated vaccine within 30 days prior to the first dose of trial drug.
• \. Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study intervention.
• \. Has an active autoimmune disease or inflammatory disorder that has required systemic treatment in the past 2 years.

Sponsors & Collaborators

• Fundación GECP: lead

Study Sites (18)

Hospital General Universitario de Alicante

Alicante, Alicante, 03010, Spain

Location

ICO Badalona, Hospital Germans Trias i Pujol

Badalona, Barcelona, 08916, Spain

Location

Hospital Universitari Vall d' Hebron

Barcelona, Barcelona, 08035, Spain

Location

Hospital Clínic De Barcelona

Barcelona, Barcelona, 08036, Spain

Location

Hospital de la Santa Creu i Sant Pau

Barcelona, Barcelona, 08041, Spain

Location

Hospital Parc Taulí

Barcelona, Barcelona, 08208, Spain

Location

Hospital De Basurto

Bilbao, Bilbao, 48013, Spain

Location

ICO Girona, Hospital Josep Trueta

Girona, Girona, 17007, Spain

Location

Hospitalario Universitario A Coruña

A Coruña, La Coruña, 15006, Spain

Location

Hospital Universitario Lucus Augusti

Lugo, Lugo, 27003, Spain

Location

Hospital Universitario Fundación Jiménez Díaz

Madrid, Madrid, 28040, Spain

Location

Hospital 12 De Octubre

Madrid, Madrid, 28041, Spain

Location

Hospital Universitario Puerta de Hierro

Majadahonda, Madrid, 28222, Spain

Location

Hospital Universitario Regional de Málaga

Málaga, Málaga, 29010, Spain

Location

Hospital Son Espases

Palma de Mallorca, Palma de Mallorca, 07120, Spain

Location

Complejo Hospitalario de Navarra

Pamplona, Pamplona, 31008, Spain

Location

Hospital Clínico de Valencia

Valencia, Valencia, 46010, Spain

Location

Hospital General Universitario de Valencia

Valencia, Valencia, 46014, Spain

Location

Related Links

• Description Web page of the sponsor where users can find more information about Fundacion GECP studies.

MeSH Terms

Conditions

Lung Neoplasms

Interventions

lenvatinib; pembrolizumab; Etoposide; Carboplatin

Condition Hierarchy (Ancestors)

Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

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

Study Officials

• Noemí Reguart, MD

  Principal Investigator of Fundación Grupo Español de Cáncer de Pulmón

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 17, 2022
• First Posted: May 20, 2022
• Study Start: November 7, 2022
• Primary Completion (Estimated): July 30, 2027
• Study Completion (Estimated): December 30, 2027
• Last Updated: April 30, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

ES (18)