A Study of a Selective T Cell Receptor (TCR) Targeting, Bifunctional Antibody-fusion Molecule STAR0602 in Participants With Advanced Solid Tumors

Study Overview
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Brief Summary
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This is an open label, multicenter, phase 1/2 study to assess the safety/tolerability and preliminary clinical activity of STAR0602 as a single agent administered intravenously in participants with advanced solid tumors that are antigen-rich.

Detailed Description
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This Phase 1/2 study consists of two parts: Phase 1 Dose Escalation and Phase 2 Dose Expansion. In Phase 1 Dose Escalation, STAR0602 will be administered intravenously in participants with advanced solid tumors to assess safety/tolerability profile of STAR0602 and to determine the maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D) of STAR0602. In Phase 2 Dose Expansion, STAR0602 at RP2D will be administered to participants with advanced, antigen-rich solid tumors to further evaluate safety and assess preliminary clinical activity of STAR0602. Clinical activity will be evaluated by objective tumor response rate (ORR), duration of response (DOR), disease control rate (DCR), and progression free survival (PFS).

Official Title
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A Phase 1/2, First-in-Human, Open-Label, Dose Escalation and Expansion Study of STAR0602, a Selective T Cell Receptor (TCR) Targeting, Bifunctional Antibody-fusion Molecule, in Subjects With Unresectable, Locally Advanced, or Metastatic Solid Tumors That Are Antigen-rich (START-001)

Conditions
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Advanced Solid Tumors, Genital Neoplasm, Female, Urogenital Neoplasms, Lung Neoplasm, Neoplasms by Site, Papillomavirus Infection, Epstein-Barr Virus Infections, Carcinoma, Neoplasms, Vulvar Neoplasms, Vulvar Diseases, Abdominal Neoplasm

Intervention / Treatment
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* Drug: STAR0602


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants must have histologically confirmed solid tumors that are unresectable, locally advanced, or metastatic and for which standard curative therapies do not exist or are no longer effective. For Phase 1, participants must have one of the following solid tumors: High mutational burden (TMB-H) Microsatellite Instability (MSI-H)/DNA mismatch repair (dMMR) Virally associated tumors For Phase 2, participants must have one of the following solid tumors: TMB-H MSI-H/dMMR Virally associated tumors Metastatic triple negative breast cancer Relapsed and refractory epithelial ovarian cancer Metastatic castration-resistance prostate cancer K-Ras wild type colorectal cancer (CRC) K-Ras mutant CRC Primary stage IV or recurrent non-small cell lung cancer (Other tumor histologies may also be included in Phase 2 as additional data emerge to support their inclusion.) Symptomatic central nervous system (CNS) metastases must have been treated, be asymptomatic for ≥ 14 days, and meet the following at the time of enrollment: No concurrent treatment for CNS disease (e.g., surgery, radiation, corticosteroids > 10 mg prednisone/day or equivalent); No concurrent leptomeningeal disease or cord compression. Exclusion Criteria: Participants with a history of known autoimmune disease with exceptions of: Vitiligo; Psoriasis, atopic dermatitis or other autoimmune skin condition not requiring systemic treatment; History of Graves' disease, now euthyroid for > 4 weeks; Hypothyroidism managed by thyroid replacement; Alopecia; Arthritis managed without systemic therapy beyond oral nonsteroidal anti-inflammatory drugs. Adrenal insufficiency well controlled on replacement therapy. Major surgery or traumatic injury within 8 weeks before first dose of study drug. Unhealed wounds from surgery or injury. Treatment with >10 mg per day of prednisone (or equivalent) or other immune-suppressive drugs within 7 days prior to the initiation of study drug. Exceptions may be made for patients who have had allergic reaction to iodinated contrast media. Steroids for topical, ophthalmic, inhaled, or nasal administration are allowed. Clinically significant cardiovascular/vascular disease, gastrointestinal disorders, inflammatory processes, pulmonary compromises Active viral, bacterial, or systemic fungal infection requiring parenteral treatment within 7 days prior to the initiation of study drug. Vaccination with any live virus vaccine within 4 weeks prior to the initiation of study drug administration. Inactivated annual influenza vaccination is allowed. Participants who are known to be human immunodeficiency virus positive or hepatitis B or C positive and have uncontrolled disease. Second primary invasive malignancy not in remission for ≥ 1 year. Exceptions include non-melanoma locally advanced skin cancer, cervical carcinoma in situ, localized prostate cancer (Gleason score ≤ 7), resected melanoma in situ, or any malignancy considered to be indolent and never required systemic therapy, with the exception of indolent lymphomas. Pregnant, likely to become pregnant, or lactating women (where pregnancy is defined as the state of a female after conception and until the termination of gestation).

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: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Phase 1: Advanced Solid Tumors<br>Dose Escalation; Intervention: Drug: STAR0602 | Drug: STAR0602<br>* solution, intravenous infusion<br>|
| Experimental: Phase 2: Advanced Solid Tumors<br>Dose Expansion; Recommended Phase 2 Dose (RP2D) identified from Phase 1 will be used in Phase 2; Intervention: Drug: STAR0602 | Drug: STAR0602<br>* solution, intravenous infusion<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Phase 1 (Dose Escalation):Number of Participants with Dose-limiting Toxicities (DLTs) in Cycle 1 |  | Cycle 1 (Cycle length= 28 days) | 
| Phase 1 and 2 (Dose Escalation and Expansion): Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) |  | Up to 3 years | 
| Phase 2 (Dose Expansion): Percentage of Participants with Overall Objective Tumor Responses (ORR) | Complete response (CR) and partial response (PR) | Up to 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Phase 1 and 2 (Dose Escalation and Expansion): Percentage of Participants with ORR |  | Up to 3 years | 
| Phase 1 and 2 (Dose Escalation and Expansion): Duration of Responses (DOR) |  | Up to 3 years | 
| Phase 1 and 2 (Dose Escalation and Expansion): Percentage of Participants with Disease Control (CR, PR, and Stable Disease) |  | Up to 3 years | 
| Phase 2 (Dose Expansion): Progression Free Survival (PFS) |  | Up to 3 years | 
| Phase 2 (Dose Expansion): Overall Survival (OS) |  | Up to 3 years | 
| Phase 1 and 2 (Dose Escalation and Expansion): Maximum Observed Plasma Concentration (Cmax) for STAR0602 |  | Dose Escalation: Cycle 1 and Cycle 6 at predefined intervals up to 1 year; Dose Expansion: Cycle 1, Cycle 3, and Cycle 6 at predefined intervals up to 3 years (Cycle length= 28 days) | 
| Phase 1 and 2 (Dose Escalation and Expansion): Time (Tmax) to Reach the Maximum Plasma Concentration (Cmax) for STAR0602 |  | Dose Escalation: Cycle 1 and Cycle 6 at predefined intervals up to 1 year; Dose Expansion: Cycle 1, Cycle 3, and Cycle 6 at predefined intervals up to 3 years (Cycle length= 28 days) | 
| Phase 1 and 2 (Dose Escalation and Expansion): Area Under the Plasma Concentration (AUC) Versus Time Curve for STAR0602 |  | Dose Escalation: Cycle 1 and Cycle 6 at predefined intervals up to 1 year; Dose Expansion: Cycle 1, Cycle 3, and Cycle 6 at predefined intervals up to 3 years (Cycle length= 28 days) | 
| Phase 1 and 2 (Dose Escalation and Expansion): Terminal Elimination Half-life (t1/2) for STAR0602 |  | Dose Escalation: Cycle 1 and Cycle 6 at predefined intervals up to 1 year; Dose Expansion: Cycle 1, Cycle 3, and Cycle 6 at predefined intervals up to 3 years (Cycle length= 28 days) | 
| Phase 1 and 2 (Dose Escalation and Expansion): Apparent Total Body Clearance (CL) for STAR0602 |  | Dose Escalation: Cycle 1 and Cycle 6 at predefined intervals up to 1 year; Dose Expansion: Cycle 1, Cycle 3, and Cycle 6 at predefined intervals up to 3 years (Cycle length= 28 days) | 
| Phase 1 and 2 (Dose Escalation and Expansion): Apparent Volume of Distribution (Vd) for STAR0602 |  | Dose Escalation: Cycle 1 and Cycle 6 at predefined intervals up to 1 year; Dose Expansion: Cycle 1, Cycle 3, and Cycle 6 at predefined intervals up to 3 years (Cycle length= 28 days) | 
| Phase 1 and 2 (Dose Escalation and Expansion): Anti-drug Antibody (ADA) formation |  | Dose Escalation and Expansion: Day 1 of predetermined cycles up to 3 years (Cycle length= 28 days) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Advanced Solid Tumors, STAR0602, Intravenous, Antineoplastic Agents, T Cell Receptor-targeting, Bifunctional Antibody-Fusion, Specific T Cell Activator, Tumor Mutational Burden (TMB) High, Microsatellite Instability (MSI) High, Virally Associated Malignancies, Checkpoint Inhibitor Resistance, Immunotherapy, Immune Checkpoint Inhibitor Resistance, Head and Neck Cancer, Nasopharyngeal Cancer, Non-small Cell Lung Cancer, Small Cell Lung Cancer, Biliary Cancer, Melanoma, Merkel Cell Carcinoma, Skin Squamous Cell Carcinoma, Skin Basal Cell Carcinoma, Endometrial Cancer, Colorectal Cancer, Small Bowel Cancer, Cervical Cancer, Gastrointestinal Neoplasms, Gastric Cancer, Esophageal Cancer, Bladder Cancer