HKT288 in Solid Tumors, Including Epithelial Ovarian Cancer and Renal Cell Carcinoma

Study Overview
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Brief Summary
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A first-in-human study using HKT288 in solid tumors, including epithelial ovarian cancer and renal cell carcinoma

Official Title
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A Phase I, Multicenter, Open-label Dose Escalation and Expansion Study of HKT288, Administered Intravenously in Adult Patients With Advanced Solid Tumors, Including Epithelial Ovarian Cancer and Renal Cell Carcinoma

Conditions
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Epithelial Ovarian Cancer, Renal Cell Carcinoma

Intervention / Treatment
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* Drug: HKT288


Participation Criteria
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Eligibility Criteria
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Main Inclusion Criteria: Advanced (metastatic or locally advanced) serous epithelial ovarian, serous fallopian tubal or serous primary peritoneal cancer or advanced clear cell or papillary renal cell carcinoma who have received or are intolerant to all therapy known to confer clinical benefit for their disease, as determined by the investigator. Tumor sample is available for retrospective CDH6 expression testing Eastern Cooperative Oncology Group (ECOG) Performance status ≤2 Main Exclusion Criteria: Patient has central nervous system metastatic involvement. Patients with previously treated CNS metastases are also excluded. Patient with any active or chronic corneal disorders Patients with monocular vision or have media opacities or any other condition that precludes monitoring of the retina or fundus. Patients with a history of serious allergic reactions Patients with QTcF >470 msec at screening ECG or congenital long QT syndrome Any prior history of treatment with maytansine (DM1 or DM4)-based ADC Patient have received anti-cancer therapies within the following time frames prior to the first dose of study treatment: Conventional cytotoxic chemotherapy: ≤4 weeks (≤ 6 weeks for nitrosoureas and mitomycin-C) Biologic therapy (e.g., antibodies): ≤4 weeks Non-cytotoxic small molecule therapeutics: ≤5 half-lives or ≤2 weeks (whichever is longer) Other investigational agents: ≤4 weeks Radiation therapy (except for localized radiotherapy for analgesic purpose or for lytic lesions at risk of fracture): ≤4 weeks Radiation therapy (localized radiotherapy for analgesic purpose or for lytic lesions at risk of fracture) ≤2 weeks Major surgery: ≤2 weeks

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dose escalation part<br>Includes patients with serous epithelial ovarian cancer (inclusive of fallopian tubal and peritoneal cancer) and clear cell or papillary renal cell carcinoma | Drug: HKT288<br>* Cadherin-6-targeting antibody-drug conjugate for intravenous administration<br>|
| Experimental: Dose expansion part (RCC arm)<br>Includes patients with clear cell or papillary renal cell carcinoma | Drug: HKT288<br>* Cadherin-6-targeting antibody-drug conjugate for intravenous administration<br>|
| Experimental: Dose expansion part (ovarian cancer arm)<br>Includes patients with serous epithelial ovarian cancer (inclusive of fallopian tubal and peritoneal cancer) | Drug: HKT288<br>* Cadherin-6-targeting antibody-drug conjugate for intravenous administration<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of dose limiting toxicities (DLTs) in the DLT evaluation period |  | evaluation period is 21 days | 
| Safety assessed by overall incidence of adverse events (AEs) and serious adverse events (SAEs) |  | Until 105 days after last dose of study treatment (=average of approximately 6 months after first dose) | 
| Tolerability as assessed by numbers of dose changes or interruptions |  | Until last dose of study treatment (=average of approximately 6 months after first dose) | 
| Safety assessed by severity of adverse events (AEs) and serious adverse events (SAEs) |  | Until 105 days after last dose of study treatment (=average of approximately 6 months after first dose) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Concentration vs. time profiles of total antibody (tAb) |  | On treatment up to Cycle 6 Day 1 and at the time of study treatment discontinuation (=average of approximately 6 months after first dose). 1 cycle is 21 days, increases to 28 days if there is a dose delay of 7 days for the start of next dose | 
| Objective response rate |  | every 2 cycles up to Cycle 17 and every 3 cycles thereafter until study treatment discontinuation (=average of approximately 6 months after first dose). Then every 9 weeks until end of disease progression follow-up (up to 12 months) | 
| Duration of response |  | every 2 cycles up to Cycle 17 and every 3 cycles thereafter until study treatment discontinuation (=average of approximately 6 months after first dose). Then every 9 weeks until end of disease progression follow-up (up to 12 months) | 
| Progression-free survival |  | every 2 cycles up to Cycle 17 and every 3 cycles thereafter until study treatment discontinuation (=average of approximately 6 months after first dose). Then every 9 weeks until end of disease progression follow-up (up to 12 months) | 
| Disease Control Rate |  | At 6 months on treatment | 
| Best overall response |  | every 2 cycles up to Cycle 17 and every 3 cycles thereafter until study treatment discontinuation (=average of approximately 6 months after first dose). Then every 9 weeks until end of disease progression follow-up (up to 12 months) | 
| Presence of anti-HKT288 antibodies. |  | On treatment up to Cycle 6 Day 1 and at the time of study treatment discontinuation (=average of approximately 6 months after first dose) | 
| CDH6 expression level |  | 3 months | 
| Pharmacokinetics (PK) parameter (AUC) for HKT288 |  | On treatment up to Cycle 6 Day 1 and at the time of study treatment discontinuation (=average of approximately 6 months after first dose) | 
| PK parameter (Cmax) for HKT288 |  | On treatment up to Cycle 6 Day 1 and at the time of study treatment discontinuation (=average of approximately 6 months after first dose) | 
| PK parameter (Tmax) for HKT288 |  | On treatment up to Cycle 6 Day 1 and at the time of study treatment discontinuation (=average of approximately 6 months after first dose) | 
| PK parameters (half-life) for HKT288 |  | On treatment up to Cycle 6 Day 1 and at the time of study treatment discontinuation (=average of approximately 6 months after first dose) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HKT288, CDH6, ADC, maytansine, epithelial ovarian cancer, renal cell carcinoma, RCC