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

Sponsor

Novartis Pharmaceuticals (Industry)

Overall Status

Terminated

CT.gov ID

NCT02947152

Collaborator

(none)

Enrollment

Locations

Arms

9.4

Actual Duration (Months)

1.5

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Epithelial Ovarian Cancer Renal Cell Carcinoma	Drug: HKT288	Phase 1

Study Design

Study Type:

Interventional

Actual Enrollment :

9 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Dec 1, 2016

Actual Primary Completion Date :

Sep 14, 2017

Actual Study Completion Date :

Sep 14, 2017

Arms and Interventions

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

Arm

Intervention/Treatment

Experimental: Dose escalation part

Includes patients with serous epithelial ovarian cancer (inclusive of fallopian tubal and peritoneal cancer) and clear cell or papillary renal cell carcinoma

Drug: HKT288

Cadherin-6-targeting antibody-drug conjugate for intravenous administration

Experimental: Dose expansion part (RCC arm)

Includes patients with clear cell or papillary renal cell carcinoma

Drug: HKT288

Cadherin-6-targeting antibody-drug conjugate for intravenous administration

Experimental: Dose expansion part (ovarian cancer arm)

Includes patients with serous epithelial ovarian cancer (inclusive of fallopian tubal and peritoneal cancer)

Drug: HKT288

Cadherin-6-targeting antibody-drug conjugate for intravenous administration

Outcome Measures

Primary Outcome Measures

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

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)]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Novartis Investigative Site	Houston	Texas	United States	77030
2	Novartis Investigative Site	Melbourne	Victoria	Australia	3000
3	Novartis Investigative Site	Leuven		Belgium	3000
4	Novartis Investigative Site	Nagoya	Aichi	Japan	466 8560
5	Novartis Investigative Site	Barcelona	Catalunya	Spain	08035
6	Novartis Investigative Site	Locarno		Switzerland	6600