Safety and Tolerability of HTI-1066 in Subjects With Advanced Solid Tumors

A Two-Part, Phase 1, Open-Label, Multicenter, Non-Randomized, Dose Escalation/Expansion Study to Evaluate the Safety and Tolerability of HTI-1066 in Subjects With Advanced Solid Tumors

HTI-1066 is a novel ADC being developed for the treatment of cancers in patients with overexpression of c-Met. This 2-part, Phase 1 study evaluates the safety the tolerability of HTI-1066 in subjects with advanced solid tumors.

Study Overview

• Status: Unknown
• Conditions: Solid Tumor, Adult
• Intervention / Treatment: Drug: HTI-1066 dose level 1; Drug: HTI-1066 dose level 2; Drug: HTI-1066 dose level 3; Drug: HTI-1066 dose level 4

Detailed Description

This is a 2-part dose escalation and dose expansion study. Dose escalation uses a modified "3+3" design and continues until a maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D) is identified. In part 2, subjects with selected tumor types will be enrolled at the MTD or RP2D.

• Study Type: Interventional
• Enrollment (Anticipated): 100
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85258
      • Recruiting
      • Honor Health Research Institute
      • Contact: Vivek Khemka, MD, MBA, FACP; Email: vivek.khemka@honorhealth.com
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Not yet recruiting
      • Sarah Cannon - Tennessee Oncology
      • Contact: Howard A Burris, MD; Email: howard.burris@sarahcannon.com
  • Texas
    • Houston, Texas, United States, 77230
      • Not yet recruiting
      • MD Anderson Cancer Center
      • Contact: Siqing Fu, MD; Phone Number: 713-792-4318; Email: siqingfu@mdanderson.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Male or female ≥18 years of age
2. Subject must have an advanced solid tumor
3. ECOG Performance Status of 0 or 1
4. Life expectancy ≥12 weeks
5. Adequate laboratory parameters
6. Female subjects agree not to be pregnant or lactating from beginning of the study screening until 4 months after receiving the last treatment; Male and female subjects and their sexual partners are willing and able to employ a highly effective method of birth control/contraception.
7. Willing and able to comply with clinic visits and study-related procedures
8. Provide signed informed consent

Exclusion Criteria:

1. Hypersensitivity to HTI-1066 or sensitivity to humanized monoclonal antibody products
2. Any concurrent therapy for cancer, radiation, or surgery within 4 weeks, except for minor palliative intent (this is to be discussed with sponsor)
3. Any concurrent use of anti-infective, anti-fungal, or anti-viral agent (exceptions are to be approved by the sponsor)
4. Any other prohibited or restricted medication as described in the study protocol.
5. Investigational therapy administered <5 half-lives before the first dose of HTI-1066
6. Any anticancer therapy administered <5 half-lives before first dose of HTI-1066; any prior immune-oncology products administered within 4 weeks or 5 half-lives before the first dose of HTI-1066 as described above; or surgery or radiotherapy administered within 4 weeks before the first dose of HTI-1066.
7. Active CNS metastases.
8. Cardiac disease (NYHA classes II-IV) including myocardial infarction within 6 months before enrollment, or unstable angina, congestive heart failure, or cardiac arrhythmia requiring treatment.
9. History or presence of an abnormal ECG, ECHO, or MUGA that is clinically meaningful.
10. History of immunodeficiency including seropositivity for human immunodeficiency virus (HIV), or other acquired or congenital immune-deficient disease, or any active systemic viral infection requiring therapy (e.g., hepatitis B or C)
11. Any other medical, psychiatric, or social condition deemed by the investigator to be likely to interfere with a subject's rights, safety, welfare or ability to sign informed consent, cooperate and participate in the study, or interfere with the interpretation of the results
12. Active infection or an unexplained fever >38.5°C during Screening or on the first scheduled day of dosing.
13. Unresolved toxicities from previous anticancer therapy.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1; One participant will receive HTI-1066 at the starting dose.	Drug: HTI-1066 dose level 1; Starting dose level
Experimental: Cohort 2; Participants will receive HTI-1066 at dose level 2.	Drug: HTI-1066 dose level 2; 2nd dose level
Experimental: Cohort 3; Participants will receive HTI-1066 at dose level 3.	Drug: HTI-1066 dose level 3; 3rd dose level
Experimental: Cohort 4; Participants will receive HTI-1066 at dose level 4.	Drug: HTI-1066 dose level 4; 4th dose level

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse events	Number of participants with AEs and SAEs	Up to 2 year
Dose-limiting toxicity (DLT)	Number of participants with DLTs	Up to 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
AUC	Area under the curve	Up to 1 year
Cmax	Peak concentration at Tmax	Up to 1 year
Anti-drug antibodies		Up to 2 year
Objective response rate		Up to 2 years
Progression-free survival (PFS)		Up to 2 years

Collaborators and Investigators

• Sponsor: Jiangsu HengRui Medicine Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): December 31, 2017
• Primary Completion (Anticipated): December 31, 2018
• Study Completion (Anticipated): December 31, 2019

Study Registration Dates

• First Submitted: December 26, 2017
• First Submitted That Met QC Criteria: January 6, 2018
• First Posted (Actual): January 12, 2018

Study Record Updates

• Last Update Posted (Actual): January 12, 2018
• Last Update Submitted That Met QC Criteria: January 6, 2018
• Last Verified: January 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: HTI-1066-101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No