itil-306 in advanced solid tumors

Conditions: Epithelial Ovarian Cancer; Non-small Cell Lung Cancer; Renal Cell Carcinoma

Summary: itil-306-201 is a phase 1a/1b, multicenter, clinical trial evaluating the safety and feasibility of itil-306 in adult participants with advanced solid tumors whose disease has progressed after standard therapy. itil-306 is a cell therapy derived from a participant's own tumor-infiltrating immune cells (lymphocytes; tils) and contains a unique molecule designed to increase til activity when it encounters folate receptor α (folr1) on the tumor.


Eligibility criteria:
key inclusion criteria: * histologically documented advanced (metastatic and/or unresectable) disease as appropriate per cohort. * phase 1a dose escalation: high-grade serous epithelial carcinoma of the ovary, fallopian tube, or peritoneum, adenocarcinoma of the lung, or clear-cell renal cell carcinoma. * phase 1b expansion: * cohort 1: high grade serous, endometrioid, or clear cell epithelial carcinoma of the ovary, fallopian tube, or peritoneum. * cohort 2: squamous-cell carcinoma or adenocarcinoma of the lung. * cohort 3: clear cell or papillary rcc. * disease must have unequivocally progressed during or after at least 1 prior line of systemic therapy that must include the following parameters (by indication): * phase 1a dose escalation and phase 1b cohort 1: participants with eoc whose disease has progressed during or after 1 prior line (at least 4 cycles) of platinum-based chemotherapy and had disease progression within 6 months from the last dose of the platinum agent. participants who received 2 or more lines of platinum therapy must have disease which has progressed on or within 6 months after the date of the last dose of the platinum agent. participants with brca-mutated eoc must have received previous parp inhibitor therapy. * phase 1a dose escalation and phase 1b cohort 2: participants with nsclc whose disease has progressed after 1 prior line of platinum-based doublet chemotherapy and a cpi. participants with targetable mutations (e.g. egfr/alk/kras) are required to have progressed on targeted therapy in addition to a platinum-based doublet chemotherapy * phase 1a dose escalation and phase 1b cohort 3: participants with rcc whose disease has progressed after 1 prior line of antiangiogenic therapy and a pd-1-axis inhibitor. * medically suitable for surgical resection of tumor tissue * following tumor resection for til harvest, will have, at minimum, 1 remaining measurable lesion as identified by ct or mri per response evaluation criteria in solid tumors (recist) v1.1 * eastern cooperative oncology group (ecog) performance status 0 or 1 * adequate bone marrow and organ function key exclusion criteria: * history of another primary malignancy within the previous 3 years * phase 1a: * eoc of the following subtypes: low-grade, endometrioid, clear cell, mucinous, sarcomatous, or mixed. * nsclc of the following subtypes: squamous, neuroendocrine differentiation. * rcc of the following subtypes: nonclear-cell rcc * phase 1b: * cohort 1: participants with mucinous, sarcomatous, and low-grade eoc. * cohort 2: participants with small cell lung cancer, or nsclc with neuroendocrine differentiation * cohort 3: participants with nonclear-cell rcc, except papillary rcc * previously received an allogeneic stem cell transplant or organ allograft * previously received til or engineered cell therapy (eg, car t-cell) * significant cardiac disease * stroke or transient ischemic attack within 12 months of enrollment * history of significant central nervous system (cns) disorder * symptomatic and/or untreated cns metastases * history of significant autoimmune disease within 2 years prior to enrollment * known history of severe, immediate hypersensitivity reaction attributed to cyclophosphamide, fludarabine, dimethyl sulfoxide (dmso), human serum albumin (has), phosphate buffer or gentamycin

Keywords: itil-306 cell therapy epithelial ovarian cancer (eoc) non-small cell lung cancer (nsclc) renal cell carcinoma (rcc) fallopian tube carcinoma tumor infiltrating lymphocytes til t-cell therapy folate receptor α (folr1) anti-folate receptor α (folr1) autologous adoptive cell therapy checkpoint, pd-1 axis inhibitor peritoneal carcinoma cellular immunotherapy immuno-oncology costimulatory antigen receptor (costar)