Phase I-II Study to Assess the Safety, Tolerability and Efficacy of PM01183 and Atezolizumab in Patients With Advanced Small Cell Lung Cancer That Progressed Following Prior Therapy With Platinum-Based Chemotherapy.
Prospective, open-label, uncontrolled and multicenter phase I-II study in SCLC patients with ECOG PS 0-1 who have failed one prior platinum-containing line but no more than one chemotherapy-containing line. The study will be divided into two parts: a dose-ranging phase I with escalating doses of PM01183 in combination with a fixed dose of atezolizumab, followed by a single-arm phase II part with expansion at the RD determined during the phase I.
• Voluntarily signed and dated written informed consent prior to any specific study procedure.
• Age \>18 years.
• Histologically or cytologically confirmed diagnosis of extensive or limited SCLC.
• Progression to first-line platinum-based chemotherapy. For phase II part: Progression to first- line platinum-based chemotherapy or first- line platinum- based chemotherapy and immunoterapy (anti PD1/ PDL1). A chemotherapy and/ or immunotherapy- free interval (CTFI, time from the last dose of first-line chemotherapy to the occurrence of progressive disease) ≥ 30 days.
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) score ≤1.
• Measurable disease according to RECIST v.1.1. Note: irradiated lesions may qualify as target if progression has been documented.
• At least three weeks since last prior anticancer treatment (including radiotherapy) and recovery to grade ≤ 1 from any adverse event (AE) related to previous anticancer treatment (excluding sensory neuropathy, anemia, asthenia and alopecia, all grade ≤ 2) according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE, v.5).
• Adequate bone marrow, renal, hepatic, and metabolic function (assessed ≤7 days before inclusion in the study):
• Platelet count ≥100 x 109/L, hemoglobin ≥9.0 g/dL and absolute neutrophil count (ANC) ≥1.5 x 109/L.
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤3.0 x the upper limit of normal (ULN), independently of the presence of liver metastases.
• Alkaline phosphatase (AP) ≤2.5 x ULN.
• Total bilirubin ≤1.5 x ULN or direct bilirubin ≤ULN
• International Normalized Ratio (INR) \<1.5 (except if patient is on oral anticoagulation therapy).
• Calculated creatinine clearance (CrCL) ≥30 mL/minute (using Cockcroft and Gault´s formula).
• Creatine phosphokinase (CPK) ≤2.5 x ULN.
• Albumin ≥3.0 g/dL. Albumin infusion to fulfill the inclusion criterion is forbidden.
• Thyroid stimulating hormone (TSH) within institutional normal limits. If TSH is above the ULN, then a free T4 within institutional normal limits is acceptable.
• Evidence of non-childbearing status for women of childbearing potential (WOCBP). Both women and men must agree to use a highly effective contraceptive measure during the trial, for at least five months after last atezolizumab dose, and for at least six weeks (women) or 4 months (men) after last PM01183 dose. Fertile male patients with WOCBP partners must agree to refrain from fathering a child or donating sperm during the trial and up to five months after treatment discontinuation. Acceptable methods of contraception include abstinence, intrauterine device (IUD), oral contraceptive, subdermal implant and/or double barrier.