HWK-016-101 is a multicenter, open-label, first-in-human (FIH) Phase 1 study evaluating HWK-016, a targeted antibody-drug conjugate (ADC) in adult participants with advanced or metastatic solid tumors. The study employs a dose escalation and dose expansion design without a control group. The study consists of 2 parts (Part A: monotherapy and Part B: combination therapy with bevacizumab); each part has 2 phases, Phase 1a (dose escalation) and Phase 1b (dose expansion). Enrollment to Part A (Phase 1a and Phase 1b) will include ovarian and endometrial cancers. Enrollment to Part B (Phase 1a and Phase 1b) will include ovarian cancer only. A subsequent protocol amendment may evaluate additional tumor types.
HWK-016-101 is a Phase 1 study evaluating HWK-016, a mucin-16 (MUC-16) targeted antibody-drug conjugate (ADC) in adult participants with advanced or metastatic solid tumors.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
265
HWK-016 is a MUCIN-16-targeted Antibody-Drug-Conjugate (ADC) being developed for the treatment of solid tumors.
Bevacizumab administered according to the USPI in 21-day cycles
University of Arkansas - Winthrop P. Rockefeller Cancer Institute
Little Rock, Arkansas, United States
NOT_YET_RECRUITINGSTART - Los Angeles
Los Angeles, California, United States
RECRUITINGSCRI - Florida Cancer Specialists
Sarasota, Florida, United States
NOT_YET_RECRUITINGSt. Francis Medical Center (OSF Healthcare)
Peoria, Illinois, United States
NOT_YET_RECRUITINGKarmanos Cancer Center
Detroit, Michigan, United States
NOT_YET_RECRUITINGStart - Ny
Lake Success, New York, United States
RECRUITINGMemorial Sloan Kettering Cancer Center
New York, New York, United States
NOT_YET_RECRUITINGAtrium Health - Wake Forest
Charlotte, North Carolina, United States
NOT_YET_RECRUITINGOhio State University Wexner Medical Center
Columbus, Ohio, United States
NOT_YET_RECRUITINGSCRI - Sydney Kimmel Cancer Center - Jefferson Health
Philadelphia, Pennsylvania, United States
NOT_YET_RECRUITING...and 2 more locations
Determine Maximum Tolerated Dose (MTD)
Determine the highest dose of HWK-016 that can be administered without signs of toxicity, measured at the end of Cycle 1(21-day cycle) by: Incidence and severity of Adverse Events (AE). Incidence of Dose-Limiting Toxicities (DLT). Incidence of Serious Adverse Events (SAE). Evaluate the safety and tolerability of HWK-016 at the selected RDE(s) determined from Phase 1a, as monotherapy (Part A) in participants with ovarian and endometrial cancers and in combination therapy with bevacizumab (Part B) in participants with ovarian cancer
Time frame: From Cycle 1, Day 1 Until Cycle 1, Day 21 (21-day cycles)
Determine Maximum Administered Dose (MAD)
Determine the highest dose of HWK-016 administered during the dose escalation part of the study, measured at the end of Cycle 1 (21-day cycle) by: Incidence and severity of Adverse Events (AE). Incidence of Dose-Limiting Toxicities (DLT). Incidence of Serious Adverse Events (SAE). Evaluate the safety and tolerability of HWK-016 at the selected RDE(s) determined from Phase 1a, as monotherapy (Part A) in participants with ovarian and endometrial cancers and in combination therapy with bevacizumab (Part B) in participants with ovarian cancer
Time frame: From Cycle 1, Day 1 to Cycle 1, Day 21 (21-day cycles) until the MTD is reached.
Determine Recommended Dose For Expansion (RDE)
Determine the dose of HWK-016 that will be recommended for further study within the tumor types studied in this clinical trial, measured at the end of Cycle 1, Day 21 (21-day cycle) by: Incidence and severity of Adverse Events (AE). Incidence of Dose-Limiting Toxicities (DLT). Incidence of Serious Adverse Events (SAE). Evaluate the safety and tolerability of HWK-016 at the selected RDE(s) determined from Phase 1a, as monotherapy (Part A) in participants with ovarian and endometrial cancers and in combination therapy with bevacizumab (Part B) in participants with ovarian cancer.
Time frame: From Cycle 1, Day 1 to Cycle 1, Day 21 (21-day cycle) until MTD is identified.
Characterize the Volume of Distribution (Vd) of HWK-016 (ADC, total antibody, CPT116, and CPT119)
Pharmacokinetic analysis of HWK-016 in human subjects
Time frame: Cycle 1 and Cycle 4 (21-day cycles)
Maximum Concentration - Cmax of HWK-016 (ADC, total antibody, CPT116, and CPT119)
Maximum amount of study drug and drug components in blood following infusion.
Time frame: At Cycle 1 and Cycle 4 - (21-day cycles)
Time to Maximum Concentration (Tmax) of HWK-016 (ADC, total antibody, CPT116, and CPT119)
Time to reach maximum concentration of drug and drug components in blood following infusion.
Time frame: Cycle 1 and Cycle 4 - (21-day cycles)
Area Under the Concentration Time Curve (AUC) for HWK-016 (ADC, total antibody, CPT116, and CPT119)
The total area under the concentration time curve of study drug and drug components following infusion
Time frame: Cycle 1 and Cycle 4 - (21-day cycles
T1/2 - Half-life of HWK-016 (ADC, total antibody, CPT116, and CPT119)
Time for 1/2 of the infused drug to be eliminated/metabolized
Time frame: Cycle 1 and Cycle 4 - (21-day cycles)
Clearance (CL)
Measured rate at which HWK-016 is cleared from the blood following infusion.
Time frame: Cycle 1 and Cycle 4 (21-day cycles)
Assess ADA (Anti drug antibody) against HWK-016
Using a blood test, determine the risk of developing anti-drug antibodies against HWK-016 following infusion in human patients.
Time frame: Every cycle from Cycle 1, Day 1 (21-day cycles) until 30 days past the last dose of study drug for up to 24 months.
Evaluate the Overall Response Rate (ORR
Measure the response rate to the study drug by CT-scans evaluated using RECIST1.1. Evaluate preliminary antitumor activity of HWK-016 at the selected RDE(s) determined from Phase 1a, as monotherapy (Part A) in participants with ovarian and endometrial cancers and in combination therapy with bevacizumab (Part B) in participants with ovarian cancer by RECIST Version 1.1
Time frame: From Cycle 1, Day 1 (21-day cycles), every 6-weeks for the first 4 assessments and then every 6 weeks for up to 24 months until disease progression or 24 months, whichever comes first.
Evaluate Overall Survival (OS).
Measure how long a patient lives following treatment with HWK-016. Evaluate the Overall Survival at the selected RDE(s) determined from Phase 1a, as monotherapy (Part A) in participants with ovarian and endometrial cancers and in combination therapy with bevacizumab (Part B) in participants with ovarian cancer
Time frame: From Cycle 1, Day 1 (21-day cycles) until death or 24 months, whichever comes first.
Evaluate the Duration of Response (DoR) to HWK-016
Measure the time from evidence of response by CT-scan until evidence of progression of cancer. Evaluate the Duration of Response at the selected RDE(s) determined from Phase 1a, as monotherapy (Part A) in participants with ovarian and endometrial cancers and in combination therapy with bevacizumab (Part B) in participants with ovarian cancer
Time frame: From Cycle 1, Day 1 (21-day cycles) until disease progression or 24 months, whichever comes first.
Evaluate Progression-free Survival (PFS)
Measure the time from the first infusion of HWK-007 until evidence of cancer progression is detected. Evaluate the Progression Free Survival at the selected RDE(s) determined from Phase 1a, as monotherapy (Part A) in participants with ovarian and endometrial cancers and in combination therapy with bevacizumab (Part B) in participants with ovarian cancer
Time frame: From Cycle 1, Day 1 (21-day cycles) infusion to End of Study (up to 24 months)
Evaluate Disease control Rate (DCR)
Measure the time from Cycle 1, Day 1 that cancer does not worsen by RECIST1.1 criteria. Evaluate the Disease Control Rate at the selected RDE(s) determined from Phase 1a, as monotherapy (Part A) in participants with ovarian and endometrial cancers and in combination therapy with bevacizumab (Part B) in participants with ovarian cancer
Time frame: From Cycle 1, Day 1 (21-day cycles) infusion to End of Study (up to 24 months
Time to Response (TTR)
Time from Cycle 1, Day 1 infusion of HWK-016 until evidence of response via CT scan according to RECIST1.1 criteria. Evaluate the Time to Response at the selected RDE(s) determined from Phase 1a, as monotherapy (Part A) in participants with ovarian and endometrial cancers and in combination therapy with bevacizumab (Part B) in participants with ovarian cancer
Time frame: From Cycle 1, Day 1 (21-day cycles) until End of Study or 24 months, whichever comes first
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