Lurbinectedin (PM01183) Combined With Pembrolizumab in Small Cell Lung Cancer.

NCT04358237 | Completed Phase 1

• 1 other identifier: MedOPP300
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 5

Brief Summary

This is a prospective, open-label, uncontrolled and multicenter phase I/II study of PM01183 in combination with pembrolizumab in patients with relapsed small cell lung cancer (SCLC). The study will be divided into two stages:

• A dose-ranging phase I stage with escalating doses of PM01183 in combination with a fixed dose of pembrolizumab, followed by:
• A non-randomized phase II stage as an expansion study at the recommended dose (RD) determined during the phase I stage. The phase I stage will focus on the selection of the RD based on safety/tolerability, while the phase II stage will assess the overall response rate (ORR) and clinical response.

Conditions

Small Cell Lung Carcinoma

Keywords

Relapsed

Outcome Measures

Primary Outcomes (2)

• Phase I: Maximum tolerated dose (MTD) and recommended phase II dose (RD) of lurbinectedin in combination with pembrolizumab in patients with relapsed SCLC.

  The MTD will be the lowest dose level explored during dose escalation at which more than one third of evaluable patients develop a DLT in Cycle 1. The RD will be the highest dose level explored at which less than one third of evaluable patients develop a DLT during Cycle 1.

  12 months

• Phase II: Efficacy of lurbinectedin in combination with pembrolizumab in terms of overall response rate (ORR), according to RECIST 1.1, in patients with relapsed SCLC.

  ORR is defined as the percentage of evaluable patients with a confirmed response, either complete (CR) or partial (PR). The ORR will be assessed using the RECIST 1.1 on a set of measurable lesions identified at baseline as target lesions or as non-target lesions (if any), and followed until PD by an appropriate method.

  38 months

Secondary Outcomes (10)

• Phase I: Preliminary information on the clinical antitumor activity of the combination.

  28 months

• Phase I: MTD and RD of lurbinectedin in combination with pembrolizumab with mandatory primary prophylaxis with G-CSF in patients with relapsed SCLC (if DLTs of this combination are exclusively related to neutropenia).

  12 months

• Phase II: Antitumor activity of this combination as per RECIST 1.1 (and iRECIST 1.1, whenever applicable) in terms of Clinical benefit ≥3 months.

  38 months

• Phase II: Antitumor activity of this combination as per RECIST 1.1 (and iRECIST 1.1, whenever applicable) in terms of Duration of response (DOR).

  38 months

• Phase II: Antitumor activity of this combination as per RECIST 1.1 (and iRECIST 1.1, whenever applicable) in terms of Progression-free survival (PFS).

  38 months

Study Arms (1)

Experimental: lurbinectedin (PM01183) + pembrolizumab

EXPERIMENTAL

During the phase I stage, patients will start receiving pembrolizumab at a fixed dose of 200 mg as a 30-min intravenous (IV) infusion followed by lurbinectedin at a starting dose of 2.4 mg/m2 as a 1-h IV infusion on Day 1, both every 3 weeks (Q3W). Lurbinectedin dose will be escalated from the starting dose in successive cohorts of patients, with a pre-established fixed dose increase (in mg/m2) of approximately 30%. During the phase II stage, patients will receive pembrolizumab at a fixed dose of 200 mg as a 30-min IV infusion followed by lurbinectedin as a 1-h IV infusion on Day 1 Q3W at the redommended dose (RD) determined during the phase I stage. A cycle is defined as an interval of 3 weeks. No dose escalation will be allowed during the phase II stage.

Drug: Lurbinectedin; Drug: Pembrolizumab

Interventions

Lurbinectedin DRUG

Lurbinectedin will be presented as a lyophilized powder for concentrate for solution for infusion in 4-mg vials. Before use, the 4-mg vial will be reconstituted with 8 mL of sterile water for injection, to give a solution containing 0.5 mg/mL of PM01183. For administration to patients as IV infusion, reconstituted vials will be diluted with glucose 50 mg/mL (5%) or sodium chloride 9 mg/mL (0.9%) solution for infusion. PM01183 will be administered as a 1 hour IV infusion Q3W, in a minimum volume of 100 mL of solution for infusion (either 5% glucose or 0.9% sodium chloride), or a minimum volume of 250 mL if through a peripheral line, always at a fixed rate and through a pump device.

Also known as: PM01183, Zepsyre

Experimental: lurbinectedin (PM01183) + pembrolizumab

Pembrolizumab DRUG

Pembrolizumab will be supplied as a solution for infusion in a single-use vial. Each vial contains 100 mg of MK3475 (pembrolizumab) in 4 ml of solution. Pembrolizumab 200 mg will be administered as a 30 minute IV infusion Q3W.

Also known as: Keytruda

Experimental: lurbinectedin (PM01183) + pembrolizumab

Eligibility Criteria

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

You may qualify if:

• Male/female participants who are at least 18 years of age on the day of signing informed consent with histologically confirmed diagnosis of SCLC whose disease has progressed after first-line chemotherapy-based regimen will be enrolled in this study.
• At least 4 weeks since the last anticancer therapy.
• Male participants: a male participant must agree to use a contraception as detailed in Appendix 3 of this protocol during the treatment period and for at least 190 days after the last dose of study treatment and refrain from donating sperm during this period.
• Female participants: a female participant is eligible to participate if she is not pregnant (see Appendix 3), not breastfeeding, and at least one of the following conditions applies:
• Not a woman of childbearing potential (WOCBP) as defined in Appendix 3 OR
• A WOCBP who agrees to follow the contraceptive guidance in Appendix 3 during the treatment period and for at least 7 months after the last dose of study treatment.
• The participant (or legally acceptable representative if applicable) provides written informed consent for the trial.
• Have provided archival tumor tissue sample or newly obtained core or excisional biopsy of a tumor lesion not previously irradiated. Formalin-fixed, paraffin embedded (FFPE) tissue blocks are preferred to slides. Newly obtained biopsies are preferred to archived tissue.
• Note: If submitting unstained cut slides, newly cut slides should be submitted to the testing laboratory within 14 days from the date slides are cut.
• Have an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 to 1. Evaluation of ECOG PS is to be performed within 7 days prior to the date of allocation.
• Have adequate organ function as defined in the following table (Table 1). Specimens must be collected within 10 days prior to the start of study treatment.
• Recovery to NCI-CTCAE grade ≤1 or to baseline from any AE derived from previous treatment (excluding alopecia and/or cutaneous toxicity and/or peripheral sensory neuropathy and/or asthenia, all grade ≤2 and/or correctable electrolyte abnormality with supplementation).
• Patients included in the expansion cohort at the RD (stage I) and all patients included in the stage II must have:
• Measurable disease according to RECIST 1.1; and
• Documented disease progression during or immediately after last therapy according to any of the aforementioned criteria.

You may not qualify if:

• A WOCBP who has a positive urine pregnancy test within 72 hours prior to allocation (see Appendix 3). If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
• Has had prior treatment with or exposure to: a) PM01183. b) T-cell or other cell-based or biologic therapies. c) Experimental anti-tumor vaccines; therapies that target any T-cell co- stimulation or checkpoint pathways, such as anti-PD-1, anti-PD-L1, anti-PD- L2, anti-CD137, or anti CTLA-4 antibody, including ipilimumab; or other medicines specifically targeting T-cells.
• Has received prior systemic anti-cancer therapy including investigational agents within 4 weeks prior to allocation.
• Note: Participants must have recovered from all AEs due to previous therapies to ≤Grade 1 or baseline. Participants with ≤Grade 2 neuropathy may be eligible.
• Note: If participant received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting study treatment.
• Has received prior radiotherapy within 2 weeks of start of study treatment. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (≤2 weeks of radiotherapy) to non-CNS disease.
• Has had radiotherapy (RT) in more than 35% of the bone marrow.
• Has a history of previous bone marrow and/or stem cell transplantation and allogenic transplant.
• Has an impending need for RT (e.g., painful bone metastasis and/or risk of spinal cord compression).
• Has received a live vaccine within 30 days prior to the first dose of study drug. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (e.g., FluMist®) are live attenuated vaccines and are not allowed.
• Has any of the following concomitant diseases/conditions:
• History or presence of unstable angina, myocardial infarction, congestive heart failure, or clinically significant valvular heart disease within last year.
• Symptomatic arrhythmia or any uncontrolled arrhythmia requiring ongoing treatment.
• History of idiopathic, pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, idiopathic pneumonitis or evidence of active pneumonitis on screening chest CT-scan. History of radiation pneumonitis in radiation field (fibrosis) is permitted, as long as it is asymptomatic and no steroids are needed.
• Known history of active neurologic paraneoplastic syndrome.

Sponsors & Collaborators

• Antonio Calles Blanco: lead
• MedSIR: collaborator
• PharmaMar: collaborator
• Merck Sharp & Dohme LLC: collaborator

Study Sites (5)

Hospital Vall D´Hebrón

Barcelona, Spain

Location

ICO - Instituto Catalán de Oncología

Barcelona, Spain

Location

Hospital Gregorio Marañon

Madrid, Spain

Location

START - Phase I Unit - HN San Chinarro

Madrid, Spain

Location

Start - Unidad Fase I - Fundacion Jimenez Diaz

Madrid, Spain

Location

MeSH Terms

Conditions

Small Cell Lung Carcinoma; Recurrence

Interventions

PM 01183; pembrolizumab

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

Study Officials

• Antonio Calles

  Hospital Gregorio Marañon

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Physician Thoracic Oncology, Head & Neck and Sarcoma Unit Early Drug Development and Phase I Unit

Model Details: Phase I/II, Multicenter, Open-label, Clinical and Pharmacokinetic Study of Lurbinectedin (PM01183) in Combination with Pembrolizumab in Patients with Relapsed Small Cell Lung Cancer

Study Record Dates

• First Submitted: April 3, 2020
• First Posted: April 24, 2020
• Study Start: September 21, 2020
• Primary Completion: September 30, 2023
• Study Completion: May 20, 2025
• Last Updated: June 4, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

ES (5)