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

Phase 1

Terminated

• Conditions: Epithelial Ovarian Cancer; Renal Cell Carcinoma
• Interventions: Drug: HKT288

• Registration Number: NCT02947152
• Lead Sponsor: Novartis Pharmaceuticals

Brief Summary

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

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2016-09-12
• Study First Submitted QC: 2016-10-25
• Study First Posted: 2016-10-27
• Study Start: 2016-12-01
• Primary Completion: 2017-09-14
• Study Completion: 2017-09-14
• Status Verified: 2018-09
• Last Update Submitted: 2020-12-06
• Last Update Posted: 2020-12-08

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 9

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Dose escalation part	HKT288	Includes patients with serous epithelial ovarian cancer (inclusive of fallopian tubal and peritoneal cancer) and clear cell or papillary renal cell carcinoma
Dose expansion part (RCC arm)	HKT288	Includes patients with clear cell or papillary renal cell carcinoma
Dose expansion part (ovarian cancer arm)	HKT288	Includes patients with serous epithelial ovarian cancer (inclusive of fallopian tubal and peritoneal cancer)

Primary Outcome Measures

Name	Time	Method
Incidence of dose limiting toxicities (DLTs) in the DLT evaluation period	evaluation period is 21 days
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)
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)

Secondary Outcome Measures

Name	Time	Method
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)
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 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)
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)
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
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)
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)
CDH6 expression level	3 months
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)

Trial Locations

Locations (1)

Novartis Investigative Site; 🇨🇭 Locarno, Switzerland