Endometrial Cancer, Non-squamous EGFR Wt NSCLC, Ovarian Cancer, Ovarian Cancer Metastatic, Ovarian Cancer Metastatic Recurrent, Platinum Resistant Ovarian Cancer, PROC
Conditions
Keywords
PTK7, Ovarian cancer, Endometrial cancer, NSCLC, Lung cancer, Chemotherapy, ADC, Antibody-Drug-Conjugate, Solid tumor, Phase 1, Ovarian neoplasms, Endometrial neoplasms, Carcinoma, Non Small Cell Lung, Lung neoplasms, Gynecologic cancer, EGFR Wt NSCLC, Platinum Resistant Ovarian Cancer, DNA Topoisomerase I
Brief summary
HWK-007-101 is a multicenter, open-label, first-in-human (FIH) Phase 1 study evaluating HWK-007, a protein tyrosine kinase 7 (PTK7)-targeted antibody drug conjugate (ADC), in adult participants with advanced or metastatic solid tumors known to be expressing PTK7. The study employs a sequential dose escalation and dose expansion design without a control group.
Detailed description
The study consists of 2 phases, Phase 1a (dose escalation) and Phase 1b (dose expansion). In Phase 1a, participants with non-squamous Endothelial Growth Factor Receptor Wild type (EGFR Wt) NSCLC, platinum resistant ovarian cancer (PROC), and endometrial cancer will be enrolled. In Phase 1b, non-squamous EGFR Wt NSCLC expansion cohort(s) will be opened, based on the safety, tolerability, PK, and preliminary antitumor data in Phase 1a. In Phase 1a of the study, HWK-007 will initially be administered as an intravenous (IV) infusion every 3 weeks (Q3W).
Interventions
DRUGHWK-007
HWK-007 is a PTK7- targeted ADC being developed for the treatment of solid tumors.
Sponsors
Whitehawk Therapeutics, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
The study employs a sequential dose escalation and dose expansion design without a control group
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 and backfill cohorts: 1. non-squamous EGFR-Wt NSCLC 2. Endometrial carcinoma 3. Platinum Resistant Ovarian Cancer 2. Monotherapy expansion cohorts: 1. Non-squamous EGFR-Wt NSCLC 2. Additional tumor indications to be defined in a future amendment
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 Tolerated Dose (MTD) | From Cycle 1, Day 1 until Cycle 1, Day 21 (21-day cycles) | Determine the highest dose of HWK-007 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). |
| 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 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). |
| Determine the Recommended Dose for Expansion (RDE) | From Cycle 1, Day 1 to Cycle 1, Day 21 (21-day cycles) until MTD is identified. | Determine the dose that will be recommended for further study within the tumor types studied in this clinical trial 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). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Characterize the Volume of Distribution (Vd) of HWK-007 (ADC, total antibody, CPT116, and CPT119) | Cycle 1 and Cycle 4 (21-day cycles) | Pharmacokinetic analysis of HWK-007 in human subjects |
| Assess ADA (Anti drug antibody) against HWK-007 | 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-007 following infusion in human patients. |
| 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 Overall Survival (OS). | From Cycle 1, Day 1 (21-day cycles) until death or 24 months, whichever comes first. | Measure how long patient lives following treatment with HWK-007 |
| Maximum Concentration - Cmax of HWK-007 (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-007 (ADC, total antibody, CPT116, and CPT119) | At 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-007 (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. |
| T1/2 - Half-life of HWK-007 (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 |
| Clearance (CL) | Cycle 1 and Cycle 4 (21-day cycles) | Measured rate at which HWK-007 is cleared from the blood following infusion. |
| Evaluate the Duration of Response (DoR) to HWK-007 | 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 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 Disease control Rate (DCR) | From Cycle 1, Day 1 (21-day cycles) until disease progression or 24 months, whichever comes first. | Measure the time from Cycle 1, Day 1 that cancer does not worsen by RECIST1.1 criteria. |
| 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-007 until evidence of response via CT scan according to RECIST1.1 criteria. |
Countries
United States
Contacts
CONTACTClinical Trial Manager Lead
CONTACTCentral email mailbox - Whitehawk Therapeutics
STUDY_DIRECTORMargaret C Dugan, MD
Whitehawk Therapeutics
STUDY_DIRECTORAllison Upalawanna
Whitehawk Therapeutics
Outcome results
None listed