This open-label clinical trial will evaluate the safety and tolerability of NN3201 in subjects with advanced and/or metastatic solid tumors known to express c-Kit.
The drug being tested in this study is called NN3201, a c-Kit targeting fully human monoclonal antibody-drug conjugate with MMAE, administered by IV. The study will be conducted in two parts, a dose escalation phase (Part A) followed by an expansion phase (Part B). The patient population for the dose escalation phase (Part A) of the study will include patients with advanced and/or metastatic c-Kit-associated solid tumors including gastrointestinal stromal tumor (GIST), adenoid cystic carcinoma (ACC), uveal melanoma, neuroendocrine tumors (NET), and chromophobe and clear cell renal cell carcinomas (ChRCC and ccRCC). For Part A patients must have received treatment with imatinimb for GIST or be progressive/refractory, ineligible, or intolerant to available standard therapy (or subject declines standard therapy) for cKit-associated solid tumors (ACC, uveal melanoma, NET, ChRCC, or ccRCC). The primary objective of the dose escalation phase (Part A) is to determine the safety profile of NN3201 administered by IV, including the incidence and severity of adverse events (AEs), serious adverse events (SAEs), and dose-limited toxicities (DLTs) as well as the incidence of abnormal laboratory findings and abnormal vital signs. Part A will help determine the maximum tolerated dose (MTD) and/or the recommended dose(s) (RDEs) for the expansion phase (Part B). Once a recommended dose has been determined in the escalation phase (Part A), the expansion phase (Part B) will assess the safety and efficacy of NN3201 when administered at 2 RDE dose levels to subjects in two indication-specific (GIST and SCLC) expansion cohorts and one basket cohort for c-Kit positive solid tumors (excluding GIST and SCLC). All cohorts in Part B will utilize the same eligibility criteria as in Part A. Cohort B1 - GIST: up to 10 subjects with GIST will be enrolled at the MTD level (RDE1) and efficacy and safety as well as any available PK and PD data will be evaluated. Cohort B2 - SCLC: up to 10 SCLC will be enrolled at 1 dose level below MTD (MTD-1/RDE2) and efficacy and safety as well as any available PK and PD data will be evaluated. The Scientific Review Committee (SRC) may decide to enroll and additional 10 subjects in SCLC subjects. Cohort B3 - c-Kit-associated solid tumors: in this basket cohort, up to 10 subjects with any c-Kit-associated solid tumor (including ACC, uveal melanoma, NET, ChRCC, and ccRCC and excluding GIST and SCLC) will be enrolled. The safety and tolerability of NN3201 administered intravenously (IV) at up to two RDEs in subjects with advanced and/or metastatic solid tumors is the primary objective for Part B.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
67
A c-Kit targeting fully human monoclonal antibody-drug conjugate with MMAE administered intravenously.
University of Michigan Hospitals
Ann Arbor, Michigan, United States
RECRUITINGCase Comprehensive Cancer Center
Cleveland, Ohio, United States
RECRUITINGOregon Health & Science University
Portland, Oregon, United States
RECRUITINGThe University of Texas MD Anderson Cancer Center
Houston, Texas, United States
RECRUITINGNEXT Virginia
Fairfax, Virginia, United States
ACTIVE_NOT_RECRUITINGNumber of subjects with Dose-limiting Toxicities:
A DLT is defined as an AE that meets at least one of the criteria listed in protocol, according to National Cancer Institute (NCI) common terminology criteria for AE (CTCAE) version 5.0 and is considered by the investigator to be clinically relevant and attributed to the study treatment during the first 21 days after the first dose of study treatment.
Time frame: 3 weeks
Incidence of Adverse Events:
Number of subjects with adverse events (AEs) according to severity, seriousness, and relationship to study drug
Time frame: 1 year
Choose which dose(s) will be used in the expansion cohorts
Assessing which dose(s) have anti-tumor benefit and an acceptable incidence of adverse events that allow for continued enrollment
Time frame: 1 year
Pharmacokinetics (PK) of NN3201
Pharmacokinetics (PK) of NGM120 by measuring serum concentration of NGM120 at specified timepoints
Time frame: 3 years
Assessment of anti-tumor activity
Assessment of anti-tumor activity by RECIST 1.1
Time frame: 3 years
Choose which dose(s) may be used in a future study
Assessing which dose(s) have anti-tumor benefit and an acceptable incidence of adverse events that may be used in a future study.
Time frame: 3 years
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