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

Phase 1

Recruiting

• Conditions: Genital Neoplasm, Female; Urogenital Neoplasms; Lung Neoplasm; Neoplasms by Site; Papillomavirus Infection; Epstein-Barr Virus Infections; Advanced Solid Tumors; Carcinoma; Neoplasms; Vulvar Neoplasms
• Interventions: Drug: STAR0602

• Registration Number: NCT05592626
• Lead Sponsor: Marengo Therapeutics, Inc.

Brief Summary

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

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).

Study Timeline

• Study First Submitted: 2022-10-13
• Study First Submitted QC: 2022-10-17
• Study First Posted: 2022-10-24
• Study Start: 2023-01-04
• Status Verified: 2024-10
• Last Update Submitted: 2024-10-22
• Last Update Posted: 2024-10-24
• Primary Completion: 2026-10
• Study Completion: 2026-10

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 365

Inclusion Criteria

1. 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 or have intolerable toxicities. Subjects should not have received more than three lines of prior therapies for their advanced or metastatic diseases.

2. For Phase 1, participants must have one of the following solid tumors:

   1. High mutational burden (TMB-H)
   2. Microsatellite Instability (MSI-H)/DNA mismatch repair (dMMR)
   3. Virally associated tumors

3. For Phase 2, participants must have one of the following solid tumors:

   1. TMB-H
   2. MSI-H/dMMR
   3. CRC (both Ras wild type and mutant)
   4. Virally associated tumors
   5. Metastatic triple negative breast cancer
   6. Platinum-resistant epithelial ovarian cancer
   7. Metastatic castration-resistance prostate cancer
   8. Primary stage IV or recurrent non-small cell lung cancer
   9. Immunogenic solid tumors

   (Other tumor histologies may also be included in Phase 2 as additional data emerge to support their inclusion.)

4. 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.

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Exclusion Criteria

1. 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.

2. Major surgery or traumatic injury within 8 weeks before first dose of study drug.

3. Unhealed wounds from surgery or injury.

4. 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.

5. Clinically significant cardiovascular/vascular disease, gastrointestinal disorders, inflammatory processes, pulmonary compromises

6. Active viral, bacterial, or systemic fungal infection requiring parenteral treatment within 7 days prior to the initiation of study drug.

7. Vaccination with any live virus vaccine within 4 weeks prior to the initiation of study drug administration. Inactivated annual influenza vaccination is allowed.

8. Participants who are known to be human immunodeficiency virus positive or hepatitis B or C positive and have uncontrolled disease.

9. 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.

10. 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).

11. Hepatic metastases unless adequately treated, either locally (e.g., by surgery, radiofrequency ablation, or chemoembolization) or systemically or both, and stable for 3 months.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Phase 1: Advanced Solid Tumors	STAR0602	Dose Escalation; Intervention: Drug: STAR0602
Phase 2: Advanced Solid Tumors	STAR0602	Dose Expansion; Recommended Phase 2 Dose (RP2D) identified from Phase 1 will be used in Phase 2; Intervention: Drug: STAR0602

Primary Outcome Measures

Name	Time	Method
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)	Up to 3 years	Complete response (CR) and partial response (PR)

Secondary Outcome Measures

Name	Time	Method
Phase 2 (Dose Expansion): Progression Free Survival (PFS)	Up to 3 years
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): 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): Anti-drug Antibody (ADA) formation	Dose Escalation and Expansion: Day 1 of predetermined cycles 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 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): 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)

Trial Locations

Locations (10)

Dana-Farber Cancer Institute; 🇺🇸 Boston, Massachusetts, United States

Institute Gustave Roussy; 🇫🇷 Villejuif, France

Vall d'Hebron Institute of Oncology; 🇪🇸 Barcelona, Cataluna, Spain

Princess Margaret Cancer Centre; 🇨🇦 Toronto, Ontario, Canada

AdventHealth Celebration; 🇺🇸 Celebration, Florida, United States

Massachusetts General Hospital Cancer Center; 🇺🇸 Boston, Massachusetts, United States

Memorial Sloan-Kettering Cancer Center; 🇺🇸 New York, New York, United States

University of Miami Sylvester Comprehensive Cancer Center; 🇺🇸 Miami, Florida, United States

The Ohio State University Comprehensive Cancer Center; 🇺🇸 Columbus, Ohio, United States

National Institutes of Health; 🇺🇸 Bethesda, Maryland, United States