study of inbrx-105 and inbrx-105 with pembrolizumab in patients with solid tumors including head and neck cancer

Conditions: Metastatic Solid Tumors; Non-small Cell Lung Cancer; Melanoma; Head and Neck Squamous Cell Carcinoma; Gastric Adenocarcinoma; Renal Cell Carcinoma; Esophageal Adenocarcinoma; Nasopharyngeal Carcinoma; Oropharyngeal Carcinoma

Summary: this is a first-in-human, open-label, nonrandomized, four-part trial to determine the safety profile and identify the maximum tolerated dose (mtd) and/or recommended phase 2 dose (rp2d) of inbrx-105 and inbrx-105 in combination with pembrolizumab. inbrx-105, a next generation bispecific antibody, targets the human programmed death-ligand 1 (pd-l1) receptor and the human 4-1bb receptor. inbrx-105 provides localized conditional t-cell co-stimulation through 4-1bb agonism.


Eligibility criteria:
inclusion criteria: * parts 1 and 3 (escalation cohorts; completed): patients with locally advanced or metastatic non-resectable solid tumors, whose disease has progressed despite standard therapy and for whom no further standard therapy exists. * part 2 (expansion cohorts): patients with non-small cell lung cancer, cutaneous melanoma, head and neck squamous cell carcinoma or solid tumors amenable to paired biopsies, with locally advanced or metastatic, non-resectable disease, which has progressed despite standard therapy or for whom no standard or clinically acceptable therapy exists. * part 4 relapsed or refractory to cpi cohorts: nsclc, cutaneous melanoma, hnscc, msi/tmb-high or mmrd solid tumors * part 4 cpi naive cohorts: locally advanced or metastatic, non-resectable nsclc or hnscc * refractory or relapsed to anti-pd-1 or anti-pd-l1, and anti-ctla4 if applicable (note: for all tumor types with checkpoint inhibitor approvals) with exception of the treatment naive nsclc cohort. * pd-l1 positivity by immunohistochemistry (ihc): parts 1 and 3 (escalation cohorts) pd-l1 positivity is not required. parts 2 and 4 (expansion cohorts): combined positive score (cps) or tumor proportion score (tps) above certain thresholds as defined per protocol. * adequate hematologic, coagulation, hepatic and renal function as defined per protocol. * eastern cooperative oncology group performance status (ecog ps) of 0 or 1. exclusion criteria: * prior exposure to 4-1bb agonists. * receipt of any investigational product or any approved anticancer drug(s) or biological product(s) within 4 weeks prior to the first dose of study drug. exceptions: hormone replacement therapy, testosterone, or oral contraceptives. note: previous exposure to anti-pd-l1 checkpoint inhibitor requires a minimum washout period of 24 weeks prior to the first dose of study drug. * hematologic malignancies (e.g., all, aml, mds, cll, cml, nhl, hodgkin lymphoma and multiple myeloma). * prior or concurrent malignancies. exception: subjects with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessments of inbrx-105. * known or active primary central nervous system (cns) tumors, leptomeningeal disease and cns metastases. exception: subjects with previously treated, asymptomatic, and clinically stable cns metastases may be allowed study entry if certain criteria apply. * grade ≥ 3 immune-related adverse events (iraes) or irae that lead to discontinuation of prior immunotherapy. some exceptions as defined per protocol apply. * active autoimmune disease or documented history of autoimmune disease that required systemic steroids or other immunosuppressive medications. certain exceptions as defined in protocol apply. * treatment with systemic immunosuppressive medications within 4 weeks prior to the first dose of study drug. certain exceptions as defined in protocol apply. * history of hepatitis b, hepatitis c, or human immunodeficiency virus (hiv). exceptions as defined in protocol for expansion cohorts will apply. * history of hepatitis or cirrhosis (e.g., non-alcohol steatohepatitis, alcohol or drug-related, autoimmune, hepatitis b, or hepatitis c). exceptions as defined in protocol for expansion cohorts will apply. * active interstitial lung disease (ild) or pneumonitis or a history of ild or pneumonitis requiring treatment with steroids or other immunosuppressive medications. * clinically significant cardiac condition, including myocardial infarction, uncontrolled angina, cerebrovascular accident, or other acute uncontrolled heart disease \< 3 months; left ventricular ejection fraction (lvef) \< 50%; new york heart association (nyha) class iii or iv congestive heart failure; or uncontrolled hypertension. * active, hemodynamically significant pulmonary embolism within 3 months prior to enrollment on this trial. * major surgery within 4 weeks prior to enrollment on this trial. * anti-infectious drug treatments (i.e., antibiotics) within 4 weeks prior to the first dose of study drug. * prior organ allograft transplantations or allogeneic peripheral blood stem cell (pbsc) or bone marrow (bm) transplantation.

Keywords: solid tumors lung cancer melanoma head and neck cancer stomach cancer gastric cancer kidney cancer renal cell carcinoma renal cancer urothelial carcinoma pdl1 41bb pd-l1 4-1bb pembrolizumab keytruda nasopharyngeal carcinoma oropharyngeal carcinoma