Clinical Trial of Lurbinectedin (PM01183) in Selected Advanced Solid Tumors

• ClinicalTrials.gov Identifier: NCT02454972
• Recruitment Status: Completed
• First Posted: May 27, 2015
• Results First Posted: November 22, 2021
• Last Update Posted: March 2, 2023
• Sponsor: PharmaMar
• Information provided by (Responsible Party): PharmaMar

Tracking Information

• First Submitted Date: May 6, 2015
• First Posted Date: May 27, 2015
• Results First Submitted Date: September 17, 2021
• Results First Posted Date: November 22, 2021
• Last Update Posted Date: March 2, 2023
• Actual Study Start Date: August 25, 2015
• Actual Primary Completion Date: September 18, 2020 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: October 21, 2021)

• Overall Response Rate (ORR) [ Time Frame: From the start of treatment to the date of progression or the start of a subsequent therapy or end of patient's follow-up, until Cycle 6 (21-day cycle) ]
  Overall Response Rate was defined as the percentage of patients with a confirmed response, either CR or PR, according to the RECIST v.1.1. Complete Response (CR): Disappearance of all target lesions; Partial Response (PR): ≥30% decrease in the sum of the longest diameters of target lesions compared with baseline; Progressive disease: ≥20% increase in the sum of the longest diameter of target lesions compared with the smallest-sum longest; diameter recorded or the appearance of one or more new lesions; Stable Disease: Neither PR or PD
• Response by Investigator Assessment [ Time Frame: From the start of treatment to the date of progression or the start of a subsequent therapy or end of patient's follow-up, until Cycle 6 (21-day cycle) ]
  When response is the primary endpoint, and thus all patients must have measurable disease to enter the trial, all patients included in the study must be accounted for in the report of the results, even if there are major protocol treatment deviations or if they are not evaluable. Each patient will be assigned one of the following: Complete Response: Disappearance of all target lesions; Partial Response: ≥30% decrease in the sum of the longest diameters of target lesions; Progressive disease: ≥20% increase in the sum of the longest diameter of target lesions; diameter recorded or the appearance of one or more new lesions; Stable Disease: Neither PR or PD; Inevaluable for response: specify reasons (for example: early death, malignant disease, toxicity; tumour assessments not repeated/incomplete; other). Normally, all eligible patients should be included in the denominator for the calculation of the response rate for phase II trials.

Original Primary Outcome Measures (submitted: May 21, 2015)

Overall response rate (ORR) [ Time Frame: Every two cycles until Cycle 6 or evidence of progression disease (1 cycle duration: 3 weeks) ]

Overall response rate (ORR), defined as the percentage of evaluable patients with a confirmed response, either complete (CR) or partial (PR).

Current Secondary Outcome Measures (submitted: October 21, 2021)

• Duration of Response [ Time Frame: From the start of treatment to the date of progression or the start of a subsequent therapy or end of patient's follow-up, until Cycle 6 (21-day cycle) ]
  Duration of Response by Investigator's Assessment, defined as the time between the date when the response criteria (PR or CR, whichever one is first reached) are fulfilled to the first date when disease progression (PD), recurrence or death is documented.
• Clinical Benefit [ Time Frame: From the start of treatment to the date of progression or the start of a subsequent therapy or end of patient's follow-up, until Cycle 6 (21-day cycle) ]
  Clinical Benefit Rate was defined as Overall Response Rate or Stable Disease lasting over four months (SD ≥ 4 months)
• Disease Control Rate [ Time Frame: From the start of treatment to the date of progression or the start of a subsequent therapy or end of patient's follow-up, until Cycle 6 ]
  Disease Control Rate was defined as Overall Response Rate or Stable Disease
• Progression Free Survival (PFS) [ Time Frame: From the date of first infusion to the date of progression disease, death (of any cause), or last tumor evaluation, up to an average of 5 years ]
  Progression-free Survival (PFS), defined as the period of time from the date of first infusion to the date of PD, death (of any cause), or last tumor evaluation. Progressive disease: ≥20% increase in the sum of the longest diameter of target lesions compared with the smallest-sum longest
• Progression-free Survival at 4 Months [ Time Frame: At 4 months ]
  Progression-free Survival at 4, defined as the probability of being free from progression and death after the first infusion at 4 months. Progressive disease: ≥20% increase in the sum of the longest diameter of target lesions compared with the smallest-sum longest
• Progression-free Survival at 6 Months [ Time Frame: At 6 months ]
  Progression-free Survival at 6, defined as the probability of being free from progression and death after the first infusion at 6 months. Progressive disease: ≥20% increase in the sum of the longest diameter of target lesions compared with the smallest-sum longest
• Overall Survival (OS) [ Time Frame: From the date of first infusion to the date of death or last contact, up to an average of 5 years ]
  Overall survival defined as the period of time from the date of first infusion to the date of death or last contact in case of patients lost to follow-up or alive at the clinical cutoff established for the cohort.
• Overall Survival at 6 Months [ Time Frame: At 6 months ]
  Overall Survival at 6 months defined as the probability of being alive after the first infusion at 6 months
• Overall Survival at 12 Months [ Time Frame: At 12 months ]
  Overall Survival at 12 months defined as the probability of being alive after the first infusion at 12 months

Original Secondary Outcome Measures (submitted: May 21, 2015)

• Duration of response (DR) [ Time Frame: Every two cycles until Cycle 6 or evidence of progression disease (1 cycle duration: 3 weeks) ]
• Progression free survival (PFS) [ Time Frame: Every two cycles until Cycle 6 or evidence of progression disease (1 cycle duration: 3 weeks) ]
• 1 year overall survival (1y-OS) [ Time Frame: Every two cycles until Cycle 6 or evidence of progression disease (1 cycle duration: 3 weeks) ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Clinical Trial of Lurbinectedin (PM01183) in Selected Advanced Solid Tumors
• Official Title: A Multicenter Phase II Clinical Trial of Lurbinectedin (PM01183) in Selected Advanced Solid Tumors
• Brief Summary: Multicenter, open-label, exploratory, phase II clinical trial to evaluate the efficacy and safety of PM01183 in previously treated patients with advanced solid tumors
• Detailed Description: Patients with relapsed small cell lung cancer (SCLC), head and neck carcinoma (H&N), neuroendocrine tumors (NETs), biliary tract carcinoma, endometrial carcinoma, BRCA 1/2-associated metastatic breast carcinoma, carcinoma of unknown primary site, germ cell tumors (GCTs), and Ewing's family of tumors (EFTs) will be enrolled in nine different cohorts. Up to 25 evaluable patients are planned to be enrolled in each cohort (50 in the endometrial carcinoma and 100 in the SCLC cohort).
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Advanced Solid Tumors
• Intervention: Drug: lurbinectedin (PM01183)

Study Arms

Experimental: lurbinectedin (PM01183)

lurbinectedin (PM01183) 4 mg vials of powder for concentrate for solution for infusion

Intervention: Drug: lurbinectedin (PM01183)

Publications *

• Boni V, Pistilli B, Brana I, Shapiro GI, Trigo J, Moreno V, Castellano D, Fernandez C, Kahatt C, Alfaro V, Siguero M, Zeaiter A, Longo F, Zaman K, Anton A, Paredes A, Huidobro G, Subbiah V. Lurbinectedin, a selective inhibitor of oncogenic transcription, in patients with pretreated germline BRCA1/2 metastatic breast cancer: results from a phase II basket study. ESMO Open. 2022 Oct;7(5):100571. doi: 10.1016/j.esmoop.2022.100571. Epub 2022 Aug 28.
• Longo-Munoz F, Castellano D, Alexandre J, Chawla SP, Fernandez C, Kahatt C, Alfaro V, Siguero M, Zeaiter A, Moreno V, Sanz-Garcia E, Awada A, Santaballa A, Subbiah V. Lurbinectedin in patients with pretreated neuroendocrine tumours: Results from a phase II basket study. Eur J Cancer. 2022 Sep;172:340-348. doi: 10.1016/j.ejca.2022.06.024. Epub 2022 Jul 10.
• Subbiah V, Brana I, Longhi A, Boni V, Delord JP, Awada A, Boudou-Rouquette P, Sarantopoulos J, Shapiro GI, Elias A, Ratan R, Fernandez C, Kahatt C, Cullell-Young M, Siguero M, Zeaiter A, Chawla SP. Antitumor Activity of Lurbinectedin, a Selective Inhibitor of Oncogene Transcription, in Patients with Relapsed Ewing Sarcoma: Results of a Basket Phase II Study. Clin Cancer Res. 2022 Jul 1;28(13):2762-2770. doi: 10.1158/1078-0432.CCR-22-0696.
• Fernandez-Teruel C, Fudio S, Lubomirov R. Integrated exposure-response analysis of efficacy and safety of lurbinectedin to support the dose regimen in small-cell lung cancer. Cancer Chemother Pharmacol. 2022 May;89(5):585-594. doi: 10.1007/s00280-021-04366-3. Epub 2021 Nov 5.
• Subbiah V, Paz-Ares L, Besse B, Moreno V, Peters S, Sala MA, Lopez-Vilarino JA, Fernandez C, Kahatt C, Alfaro V, Siguero M, Zeaiter A, Zaman K, Lopez R, Ponce S, Boni V, Arrondeau J, Delord JP, Martinez M, Wannesson L, Anton A, Valdivia J, Awada A, Kristeleit R, Olmedo ME, Rubio MJ, Sarantopoulos J, Chawla SP, Mosquera-Martinez J, D' Arcangelo M, Santoro A, Villalobos VM, Sands J, Trigo J. Antitumor activity of lurbinectedin in second-line small cell lung cancer patients who are candidates for re-challenge with the first-line treatment. Lung Cancer. 2020 Dec;150:90-96. doi: 10.1016/j.lungcan.2020.10.003. Epub 2020 Oct 10.
• Trigo J, Subbiah V, Besse B, Moreno V, Lopez R, Sala MA, Peters S, Ponce S, Fernandez C, Alfaro V, Gomez J, Kahatt C, Zeaiter A, Zaman K, Boni V, Arrondeau J, Martinez M, Delord JP, Awada A, Kristeleit R, Olmedo ME, Wannesson L, Valdivia J, Rubio MJ, Anton A, Sarantopoulos J, Chawla SP, Mosquera-Martinez J, D'Arcangelo M, Santoro A, Villalobos VM, Sands J, Paz-Ares L. Lurbinectedin as second-line treatment for patients with small-cell lung cancer: a single-arm, open-label, phase 2 basket trial. Lancet Oncol. 2020 May;21(5):645-654. doi: 10.1016/S1470-2045(20)30068-1. Epub 2020 Mar 27. Erratum In: Lancet Oncol. 2020 Dec;21(12):e553.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: December 20, 2018): 345
• Original Estimated Enrollment (submitted: May 21, 2015): 225
• Actual Study Completion Date: September 18, 2020
• Actual Primary Completion Date: September 18, 2020 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Age ≥ 18 years.
• Voluntary signed informed consent (IC)

• Pathologically proven diagnosis of any of the following malignancies:

  • Small cell lung cancer (SCLC).
  • Head and neck carcinoma (H&N). Salivary glands tumors are excluded.
  • Neuroendocrine tumors (NETs), grade 2 and grade 3 according to World Health Organization classification.
  • Biliary tract carcinoma.
  • Endometrial carcinoma.
  • BRCA 1/2- associated metastatic breast carcinoma
  • Carcinoma of unknown primary site.
  • Germ cell tumor (GCTs), excluding immature teratoma, or teratoma with malignant transformation.
  • Ewing's family of tumors (EFTs)

• Prior treatment. Patients must have received:

  • SCLC, endometrial carcinoma: one prior chemotherapy-containing line.
  • H&N, NETs, biliary tract, CUP: one or two prior chemotherapy-containing lines
  • GCTs: no limit of prior therapy
  • EFTs: no more than two prior chemotherapy-containing lines in the metastatic/recurrent setting.
  • BRCA 1/2-associated metastatic breast carcinoma: at least one but no more than three prior chemotherapy-containing lines.
• Performance status ≤ 2 [Eastern Cooperative Oncology Group (ECOG)]
• Adequate major organ function
• At least three weeks since the last chemotherapy
• Women of childbearing potential must have pregnancy excluded by appropriate testing before study entry

Exclusion Criteria:

• Prior treatment with PM01183 or trabectedin
• Prior or concurrent malignant disease unless in complete remission for more than five years
• Known central nervous system (CNS) involvement
• Relevant diseases or clinical situations which may increase the patient's risk
• Pregnant or breastfeeding women and fertile patients (men and women) who are not using an effective method of contraception

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Belgium, France, Germany, Italy, Spain, Sweden, Switzerland, United Kingdom, United States

Administrative Information

• NCT Number: NCT02454972
• Other Study ID Numbers: PM1183-B-005-14
• Has Data Monitoring Committee: Not Provided
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: PharmaMar
• Original Responsible Party: Same as current
• Current Study Sponsor: PharmaMar
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: PharmaMar
• Verification Date: February 2023