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

Phase 1

• Conditions: Solid Tumor, Adult
• Interventions: Drug: HTI-1066 dose level 2; Drug: HTI-1066 dose level 3; Drug: HTI-1066 dose level 4; Drug: HTI-1066 dose level 1

• Registration Number: NCT03398720
• Lead Sponsor: Jiangsu HengRui Medicine Co., Ltd.

Brief Summary

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.

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 Timeline

• Study First Submitted: 2017-12-26
• Study Start: 2017-12-31
• Status Verified: 2018-01
• Study First Submitted QC: 2018-01-06
• Last Update Submitted: 2018-01-06
• Study First Posted: 2018-01-12
• Last Update Posted: 2018-01-12
• Primary Completion: 2018-12-31
• Study Completion: 2019-12-31

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 100

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Cohort 2	HTI-1066 dose level 2	Participants will receive HTI-1066 at dose level 2.
Cohort 3	HTI-1066 dose level 3	Participants will receive HTI-1066 at dose level 3.
Cohort 4	HTI-1066 dose level 4	Participants will receive HTI-1066 at dose level 4.
Cohort 1	HTI-1066 dose level 1	One participant will receive HTI-1066 at the starting dose.

Primary Outcome Measures

Name	Time	Method
Adverse events	Up to 2 year	Number of participants with AEs and SAEs
Dose-limiting toxicity (DLT)	Up to 2 years	Number of participants with DLTs

Secondary Outcome Measures

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

Trial Locations

Locations (3)

Honor Health Research Institute; 🇺🇸 Scottsdale, Arizona, United States

Sarah Cannon - Tennessee Oncology; 🇺🇸 Nashville, Tennessee, United States

MD Anderson Cancer Center; 🇺🇸 Houston, Texas, United States