Endometrial Cancer, Platinum Resistant Ovarian Cancer, PROC
Conditions
Keywords
Ovarian Cancer, Endometrial Cancer, PROC, Ovarian, Endometrial, ADC, Phase 1, Solid tumor
Brief summary
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.
Detailed description
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.
Interventions
DRUGHWK-016, MUCIN-16-targeted ADC
HWK-016 is a MUCIN-16-targeted Antibody-Drug-Conjugate (ADC) being developed for the treatment of solid tumors.
DRUGBevacizumab
Bevacizumab administered according to the USPI in 21-day cycles
Sponsors
Whitehawk Therapeutics, Inc.
Catalyst Pharmaceutical Research
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Dose escalation will use a BOIN design.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Have one of the following solid tumor cancers: 1. Monotherapy escalation, backfill and expansion cohorts: 1. Endometrial Carcinoma 2. Ovarian Cancer 2. Combination Escalation, Backfill and Expansion Cohorts a. Ovarian Cancer
Exclusion criteria
1. Individual with known or suspected uncontrolled central nervous system (CNS) metastases 2. Individual with history of carcinomatous meningitis 3. Individual with active uncontrolled systemic bacterial, viral, fungal, or parasitic infection 4. Individual with evidence of corneal keratopathy or history of cornea transplant 5. Any serious unresolved toxicities from prior therapy 6. Significant cardiovascular disease 7. Prolongation of QT interval corrected for heart rate using Fridericia's formula (QTcF) ≥ 470 milliseconds (ms) 8. History of pneumonitis/interstitial lung disease 9. Individuals who are pregnant, breastfeeding or plan to breastfeed during study or within 30 days of last dose of study intervention
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Determine Maximum Administered Dose (MAD) | From Cycle 1, Day 1 to Cycle 1, Day 21 (21-day cycles) until the MTD is reached. | 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 |
| Determine Recommended Dose For Expansion (RDE) | From Cycle 1, Day 1 to Cycle 1, Day 21 (21-day cycle) until MTD is identified. | 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. |
| Determine Maximum Tolerated Dose (MTD) | From Cycle 1, Day 1 Until Cycle 1, Day 21 (21-day cycles) | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Characterize the Volume of Distribution (Vd) of HWK-016 (ADC, total antibody, CPT116, and CPT119) | Cycle 1 and Cycle 4 (21-day cycles) | Pharmacokinetic analysis of HWK-016 in human subjects |
| Maximum Concentration - Cmax of HWK-016 (ADC, total antibody, CPT116, and CPT119) | At Cycle 1 and Cycle 4 - (21-day cycles) | Maximum amount of study drug and drug components in blood following infusion. |
| Time to Maximum Concentration (Tmax) of HWK-016 (ADC, total antibody, CPT116, and CPT119) | Cycle 1 and Cycle 4 - (21-day cycles) | Time to reach maximum concentration of drug and drug components in blood following infusion. |
| Area Under the Concentration Time Curve (AUC) for HWK-016 (ADC, total antibody, CPT116, and CPT119) | Cycle 1 and Cycle 4 - (21-day cycles | The total area under the concentration time curve of study drug and drug components following infusion |
| Evaluate the Overall Response Rate (ORR | 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. | 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 |
| Evaluate Overall Survival (OS). | From Cycle 1, Day 1 (21-day cycles) until death or 24 months, whichever comes first. | 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 |
| Evaluate the Duration of Response (DoR) to HWK-016 | From Cycle 1, Day 1 (21-day cycles) until disease progression or 24 months, whichever comes first. | 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 |
| Evaluate Progression-free Survival (PFS) | From Cycle 1, Day 1 (21-day cycles) infusion to End of Study (up to 24 months) | 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 |
| Evaluate Disease control Rate (DCR) | From Cycle 1, Day 1 (21-day cycles) infusion to End of Study (up to 24 months | 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 |
| T1/2 - Half-life of HWK-016 (ADC, total antibody, CPT116, and CPT119) | Cycle 1 and Cycle 4 - (21-day cycles) | Time for 1/2 of the infused drug to be eliminated/metabolized |
| Time to Response (TTR) | From Cycle 1, Day 1 (21-day cycles) until End of Study or 24 months, whichever comes first | 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 |
| Clearance (CL) | Cycle 1 and Cycle 4 (21-day cycles) | Measured rate at which HWK-016 is cleared from the blood following infusion. |
| Assess ADA (Anti drug antibody) against HWK-016 | 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. | Using a blood test, determine the risk of developing anti-drug antibodies against HWK-016 following infusion in human patients. |
Countries
United States
Contacts
CONTACTClinical Trial Manager Lead
CONTACTCentral email mailbox - Whitehawk Therapeutics
STUDY_DIRECTORMargaret C Dugan, MD
Whitehawk Therapeutics
STUDY_DIRECTORAllison Uppalawanna
Whitehawk Therapeutics
Outcome results
None listed