a study exploring the safety and tolerability of incb081776 in participants with advanced malignancies

Conditions: Advanced Solid Tumors

Summary: the purpose of this study is to evaluate the safety and tolerability, pharmacokinetics, pharmacodynamics, and early clinical activity of single-agent incb081776 (part 1) and incb081776 in combination with incmga00012 (part 2).


Eligibility criteria:
inclusion criteria: • male and female participants at least 18 years of age with advanced malignancies who have received or been intolerant to standard therapy: parts 1a and 2a: * histologically confirmed advanced or metastatic gastric or gej adenocarcinoma, hcc, melanoma, nsclc, rcc, soft-tissue sarcoma, scchn (recurrent or metastatic), tnbc, or urothelial carcinoma. additional tumor histologies, including msi-h tumors, may be allowed with approval from the medical monitor. * measurable disease per recist v1.1. parts 1b and 2b: • histologic confirmation of the cohort-specific tumor types specified below: cohort 1 - advanced or metastatic melanoma cohort 2 - advanced or metastatic nsclc cohort 3 - recurrent or metastatic scchn cohort 4 - advanced or metastatic soft-tissue sarcoma * cohorts 1-3 must have received 1 prior pd-1/l1 treatment and have experienced pd during or after that treatment and have progressed on other soc therapy(ies); cohort 4 must be pd-1/l1 treatment naïve but have progressed on soc therapy(ies). * measurable disease per recist v1.1. * must be willing to submit to a fresh baseline tumor biopsy and an on-treatment biopsy between cycle 2 day 1 and cycle 3 day 1. * care should be taken to biopsy the same lesion for the baseline and on-treatment samples. if a participant has a solitary target lesion, this should not be biopsied. part 1c: * participants with relapsed/refractory aml following standard therapy; acute promyelocytic leukemia (m3) and therapy-related aml are excluded. * flt3-itd and idh1/2 wild-type or mutated are eligible; appropriate targeted therapy for participants with actionable mutations must have been received. exclusion criteria: * laboratory values not within the protocol-defined range. * history of retinal disease as defined in the protocol. * clinically significant cardiac disease as per protocol-defined criteria. * history or presence of an ecg that, in the investigator's opinion, is clinically meaningful as per protocol-defined criteria. * untreated brain or central nervous system (cns) metastases or brain or cns metastases that have progressed as per protocol-defined criteria. * active or inactive autoimmune disease or syndrome that has required systemic treatment in the past 2 years or receiving systemic therapy for an autoimmune or inflammatory disease. * prior grade 3 or higher immune-related aes or any ocular toxicity on prior immunotherapy as per protocol-defined criteria. * receipt of any vitamin k antagonists, systemic corticosteroids, live vaccines, or treatment with any anticancer medications or investigational drugs within the protocol-defined intervals. * has not recovered to ≤ grade 1 or baseline from toxic effects of prior therapy and/or complications from prior surgical intervention before starting study treatment. * active infection requiring systemic therapy. * evidence of hepatitis b virus or hepatitis c virus infection or risk of reactivation. * known history of hiv (hiv 1/2 antibodies).

Keywords: advanced solid tumors axl mer axl/mer pd-1