Clinical Trial of Lurbinectedin (PM01183) in Patients With Advanced Solid Tumors

NCT05063318 | Completed Phase 1 Results FDA Drug

• 1 other identifier: PM1183-A-018-20
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 2

Brief Summary

Prospective, open-label, two-way crossover, phase Ib drug-drug interaction study in patients with advanced solid tumors

Conditions

Advanced Solid Tumors

Outcome Measures

Primary Outcomes (1)

• Pharmacokinetic Analysis: Dose-adjusted AUC(0-∞)

  The primary parameter of interest for the statistical analysis will be plasma dose adjusted AUC(0-∞)

  Day 1, 2, 3, 5, 8, 11, 15, 22 (Cycle 1,2,3) (each cycle is 21 days)

Secondary Outcomes (5)

• Pharmacokinetic Analysis: Dose-normalized AUC(0-t)

  Day 1, 2, 3, 5, 8, 11, 15, 22 (Cycle 1,2,3) (each cycle is 21 days)

• Pharmacokinetic Analysis: Dose-normalized Cmax

  Day 1, 2, 3, 5, 8, 11, 15, 22 (Cycle 1,2,3) (each cycle is 21 days)

• Pharmacokinetic Analysis: T1/2

  Day 1, 2, 3, 5, 8, 11, 15, 22 (Cycle 1,2,3) (each cycle is 21 days)

• Pharmacokinetic Analysis: Total Body Clearance (CL)

  Day 1, 2, 3, 5, 8, 11, 15, 22 (Cycle 1,2,3) (each cycle is 21 days)

• Pharmacokinetic Analysis: Volume of Distribution

  Day 1, 2, 3, 5, 8, 11, 15, 22 (Cycle 1,2,3) (each cycle is 21 days)

Study Arms (2)

Sequence TR

ACTIVE COMPARATOR

Sequence 1 (TR) * Cycle 1: Itraconazole + lurbinectedin 0.8 mg/m² * Cycle 2: Lurbinectedin alone 3.2 mg/m² * Cycle 3: Lurbinectedin alone 3.2 mg/m² (optional) PART A The dose of lurbinectedin when given in combination with itraconazole for the initial three patients in Part A will be 0.8 mg/m². In Part A, all patients will receive itraconazole plus lurbinectedin in Cycle 1 and lurbinectedin alone in Cycles 2 and 3 (this last cycle being optional). PART B Randomization will apply for study Part B only. In Part B is susceptible to be adjusted properly if deemed necessary based on exposure and safety experience in Part A. In Part B, patients will be randomly assigned to the corresponding sequences.

Drug: Lurbinectedin alone; Drug: Lurbinectedin+Itraconazole co-administration

Sequence RT

ACTIVE COMPARATOR

Sequence 2 (RT): * Cycle 1: Lurbinectedin alone 3.2 mg/m² * Cycle 2: Itraconazole + lurbinectedin 0.8 mg/m² * Cycle 3: Lurbinectedin alone 3.2 mg/m² (optional)

Drug: Lurbinectedin alone; Drug: Lurbinectedin+Itraconazole co-administration

Interventions

Lurbinectedin alone DRUG

The dose of lurbinectedin during Parts A and B will be 3.2 mg/m² for all patients when administered without itraconazole.

Sequence RT; Sequence TR

Lurbinectedin+Itraconazole co-administration DRUG

The dose of lurbinectedin when given in combination with itraconazole for the initial three patients in Part A will be 0.8 mg/m², and in Part B is susceptible to be adjusted properly if deemed necessary based on exposure and safety experience in Part A.

Sequence RT; Sequence TR

Eligibility Criteria

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

You may qualify if:

• Voluntary signed and dated written informed consent prior to any specific study procedure.
• Male or female with age ≥ 18 years.
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) of ≤ 1 (App. 1).
• Life expectancy \> 3 months.
• Pathologically confirmed diagnosis of advanced solid tumors \[except for primary central nervous system (CNS) tumors\], for which no standard therapy exists.
• Recovery to grade ≤ 1 from drug-related adverse events (AEs) of previous treatments, excluding alopecia and grade 1/2 asthenia or fatigue, according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCICTCAE v.5).
• Laboratory values within fourteen days prior to Day 1 of Cycle 1
• Left ventricular ejection fraction (LVEF) by echocardiography (ECHO) or multiple-gated acquisition (MUGA) within normal range (according to institutional standards).
• Evidence of non-childbearing status for women of childbearing potential (WOCBP). WOCBP must agree to use a highly effective contraceptive measure up to six months after treatment discontinuation. Valid methods to determine the childbearing potential, adequate contraception and requirements for WOCBP partners are described in App. 2. Fertile male patients with WOCBP partners should use condoms during treatment and for four months following the last investigational medicinal product (IMP) dose.

You may not qualify if:

• Concomitant diseases/conditions:
• History or presence of unstable angina, myocardial infarction, congestive heart failure, or clinically significant valvular disease within last year.
• Symptomatic arrhythmia or any uncontrolled arrhythmia requiring ongoing treatment.
• Known cirrhosis, alcohol induced steatosis, or chronic active hepatitis. For hepatitis B, this includes positive test for both Hepatitis B surface antigen (HBsAg) and quantitative Hepatitis B polymerase chain reaction (PCR or HVB-DNA+). For hepatitis C, this includes positive test for both Hepatitis C antibody and quantitative Hepatitis C by PCR (or HVC-RNA+).
• History of obstructive cholestatic liver disease (suitable for stenting procedure) or biliary sepsis in the past 2 months.
• Known of active COVID-19 disease (this includes positive test for SARS-CoV- 2 in nasopharyngeal/oropharyngeal swabs or nasal swabs by PCR).
• Symptomatic, progressive or corticosteroids-requiring documented brain metastases or leptomeningeal disease involvement. Patients with asymptomatic documented stable brain metastases not requiring corticosteroids during the last four weeks are allowed.
• Use of (strong or moderate) inhibitors or inducers of CYP3A4 activity within three weeks prior to Day 1 of Cycle 1.
• Use of CYP3A4 substrates such as HMG-CoA reductase inhibitors such as atorvastatin, lovastatin and simvastatin for which concomitant administration with strong CYP3A4 inhibitor is contraindicated (App 3).
• Treatment with any investigational product within the 30 days before Day 1 of Cycle 1.
• Women who are pregnant or breast feeding and fertile patients (men and women) who are not using an effective method of contraception (see App 2).
• Psychiatric illness/social situations that would limit compliance with study requirements.

Sponsors & Collaborators

• PharmaMar: lead

Study Sites (2)

Fundacion Jimenez Diaz

Madrid, 28040, Spain

Location

Hospital HM Sanchinarro

Madrid, 28050, Spain

Location

MeSH Terms

Interventions

PM 01183

Results Point of Contact

• Title: Clinical Developtment, Department of PharmaMar's Oncology, Business Unit
• Organization: Pharma Mar S.A.

clinicaltrials@pharmamar.com

0034918466000

Study Officials

• Sara Martínez Gonzalez, MD

  PharmaMar

  STUDY DIRECTOR

• Rubin Lubomirov, MD, PhD

  PharmaMar

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: This is a prospective, open-label, two-way crossover, phase Ib drug-drug interaction study in patients with advanced solid tumors.

Study Record Dates

• First Submitted: September 2, 2021
• First Posted: October 1, 2021
• Study Start: October 7, 2020
• Primary Completion: April 21, 2022
• Study Completion: April 21, 2022
• Last Updated: September 2, 2025
• Results First Posted: September 2, 2025

Record last verified: 2025-08

Locations

ES (2)