Study of Lurbinectedin (PM01183) in Combination with Pembrolizumab in Patients with Relapsed Small Cell Lung Cancer

Phase 1

• Conditions: Small Cell Lung Cancer; MedDRA version: 21.1Level: PTClassification code 10041067Term: Small cell lung cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2019-002261-35-ES
• Lead Sponsor: Dr.Antonio Calles Blanco

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2020-02-28
• Last Update Posted: 19 April 2022

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 42

Inclusion Criteria

Participants are eligible to be included in the study only if all of the following criteria apply:
1. 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.
2. At least 4 weeks since the last anticancer therapy.
3. 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 120 days after the
last dose of study treatment and refrain from donating sperm during this period.
4. 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:
a.) Not a woman of childbearing potential (WOCBP) as defined in Appendix 3 OR b.) A WOCBP who agrees to follow the contraceptive guidance in Appendix 3 during the
treatment period and for at least 90 days after the last dose of study treatment.
5. The participant (or legally acceptable representative if applicable) provides written informed consent for the trial.
6. 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.
7. 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/randomization.
8. Have adequate organ function as defined in the following table (Table 1)*see protocol pages 28 & 29. Specimens must be collected within 10 days prior to the start of study treatment.
9. 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).
10. Patients included in the expansion cohort at the RD (phase I stage) and all patients included in the phase II stage must have:
a) Measurable disease according to RECIST 1.1; and
b) Documented disease progression during or immediately after last therapy according to any of the aforementioned criteria.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 20
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 22

Exclusion Criteria

1. A WOCBP who has a positive urine pregnancy test within 72 hours prior to allocation.
2. Has had prior treatment with or exposure to: PM01183, Radioimmunoconjugates, T-cell or other cell-based or biologic therapies, 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 Tcells.
3. Has received prior radiotherapy within 2 weeks of start of study treatment.
4. Has had radiotherapy (RT) in more than 35% of the bone marrow.
5. Has a history of previous bone marrow and/or stem cell transplantation and allogenic transplant.
6. Has an impending need for RT (e.g., painful bone metastasis and/or risk of spinal cord compression).
7. Has received a live vaccine within 30 days prior to the first dose of study drug.
8. Has any of the following concomitant diseases/conditions:
a)History or presence of unstable angina, myocardial infarction, congestive heart failure, or clinically significant valvular heart disease within last year.
b)Symptomatic arrhythmia or any uncontrolled arrhythmia requiring ongoing treatment.
c)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.
d)Known history of active neurologic paraneoplastic syndrome.
e)Myopathy or any clinical situation that causes significant and persistent elevation of CPK (>2.5 x ULN in two different determinations performed one week apart).
f)Limitation of the patient’s ability to comply with the treatment or follow-up protocol.
g)Any other major illness that, in the Investigator’s judgment, will substantially increase the risk associated with the patient’s participation in this study.
9. Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug.
10. Has active autoimmune disease that has required systemic treatment in the past 2 years
11. Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis
12. Has an active infection requiring systemic therapy.
13. Has a known history of Human Immunodeficiency Virus (HIV).
14. Has a known history of Hepatitis B (defined as Hepatitis B surface antigen [HBsAg] reactive) or known active Hepatitis C virus (defined as HCV RNA is detected) infection.
15. Has a known history of active tuberculosis (Mycobacterium tuberculosis).
16. Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the subject’s participation for the full duration of the study, or is not in the best interest of the subject to participate, in the opinion of the treating Investigator.
17. Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
18. 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.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified