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

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Solid Tumor, Adult

Intervention / Treatment
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* Drug: HTI-1066 dose level 1
* Drug: HTI-1066 dose level 2
* Drug: HTI-1066 dose level 3
* Drug: HTI-1066 dose level 4


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female ≥18 years of age Subject must have an advanced solid tumor ECOG Performance Status of 0 or 1 Life expectancy ≥12 weeks Adequate laboratory parameters 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. Willing and able to comply with clinic visits and study-related procedures Provide signed informed consent Exclusion Criteria: Hypersensitivity to HTI-1066 or sensitivity to humanized monoclonal antibody products Any concurrent therapy for cancer, radiation, or surgery within 4 weeks, except for minor palliative intent (this is to be discussed with sponsor) Any concurrent use of anti-infective, anti-fungal, or anti-viral agent (exceptions are to be approved by the sponsor) Any other prohibited or restricted medication as described in the study protocol. Investigational therapy administered <5 half-lives before the first dose of HTI-1066 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. Active CNS metastases. 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. History or presence of an abnormal ECG, ECHO, or MUGA that is clinically meaningful. 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) 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 Active infection or an unexplained fever >38.5°C during Screening or on the first scheduled day of dosing. Unresolved toxicities from previous anticancer therapy.

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: Cohort 1<br>One participant will receive HTI-1066 at the starting dose. | Drug: HTI-1066 dose level 1<br>* Starting dose level<br>|
| Experimental: Cohort 2<br>Participants will receive HTI-1066 at dose level 2. | Drug: HTI-1066 dose level 2<br>* 2nd dose level<br>|
| Experimental: Cohort 3<br>Participants will receive HTI-1066 at dose level 3. | Drug: HTI-1066 dose level 3<br>* 3rd dose level<br>|
| Experimental: Cohort 4<br>Participants will receive HTI-1066 at dose level 4. | Drug: HTI-1066 dose level 4<br>* 4th dose level<br>|

What is the study measuring?
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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 |