Small Cell Lung Cancer MedDRA version: 21.1 Level: PT Classification code 10041067 Term: Small cell lung cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Sponsors
Dr.Antonio Calles Blanco
Eligibility
Sex/Gender
All
Inclusion criteria
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
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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: Phase 1 stage: Until MTD and RD have been defined Phase 2 stage:Time from randomization to disease progression;Main Objective: Phase I stage: (1) Objective: To determine the MTD and the recommended phase II dose (RD) of PM01183 in combination with pembrolizumab in patients with relapsed SCLC. Phase II stage: (1) Objective: To assess the efficacy of PM01183 in combination with pembrolizumab in terms of ORR, according to RECIST 1.1, in patients with relapsed SCLC.;Secondary Objective: Phase I stage (1)to obtain preliminary information on the clinical antitumor activity of this combination in patients with relapsed SCLC (2)to determine the MTD and the RD of PM01183 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) Phase II stage (1)to further characterize the antitumor activity of this combination as per RECIST 1.1 in terms of: ORR or stable disease (SD) =3 months);DOR;PFS;OS Both stages (1)To characterize the safety profile and feasibility of PM01183 in combination with pembrolizumab in patients with relapsed SCLC (2)To characterize the plasma pharmacokinetics (PK) of PM01183 in this combination and to detect major drug-drug PK interactions (3)to perform a PGt analysis (4)to perform a PGx analysis in tumor samples of patients exposed to PM01183 and pembrolizumab in order to assess potential markers of response and/or resistance;Primary end point(s): Phase I Stage Determination of MTD and RD: •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. If the DLTs of the PM01183 and pembrolizumab combination without G-CSF prophylaxis are exclusively related to neutropenia, the MT | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Both Stages:Safety: patients will be evaluable for safety if they have received at least one partial infusion of PM01183. AEs will be graded according to the NCI-CTCAE v.5. Additionally, treatment compliance, in particular dose reduction requirements, skipped doses and/or cycle delays due to AEs, will be described. • Efficacy: preliminary antitumor activity in the phase I stage, will be evaluated according to the RECIST 1.1 (and the iRECIST 1.1, whenever applicable) at least 6 weeks after treatment initiation in all patients with measurable disease. During expansion at the RD in the phase II stage, antitumor activity will also be evaluated according to the RECIST 1.1 (and the iRECIST 1.1, whenever applicable) as described above. In both stages, a patient evaluable for efficacy should have received at least one complete cycle (including observation period) and must have had at least one tumor assessment as per RECIST 1.1, except if non-evaluability is due to treatment failure such as treatment-related AEs, death or early unequivocal PD outside the central nervous system (CNS). • Pharmacokinetics: PK parameters will be evaluated in plasma by standard noncompartmental methods (compartmental modeling may be performed if appropriate). • Pharmacogenetics: a blood sample will be collected at any time during the trial (but preferably just before treatment start in Cycle 1 along with the first PK sample) to analyze germline DNA for the presence or absence of mutations or polymorphisms in genes relevant for the metabolism and/or transport of PM01183 that may help explain individual variability in main PK parameters. • Pharmacogenomics: this exploratory analysis will be performed if there is evidence of clinical benefit in the cohort of patients with available samples for PGx analysis. The mutational status of factors involved in DNA repair mechanisms, or related to the mechanism of action of PM01183 or pembrolizumab, will be evaluated from available pr | — |
Countries
Spain
Contacts
Public ContactOperations Unit
Medica Scientia Innovation Research (MedSIR)
Outcome results
None listed