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

Neoplasms Clinical Trial

— START-001  

Official title:

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)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05592626
• Other study ID #: CP-START-001
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: January 4, 2023
• Est. completion date: October 2026

Study information

• Verified date: September 2023
• Source: Marengo Therapeutics, Inc.
• Contact: Ke Liu, MD, PhD
• Phone: +1 (617) 917-4980
• Email: kliu[@]marengotx.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 365
• Est. completion date: October 2026
• Est. primary completion date: October 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

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. Virally associated tumors

4. Metastatic triple negative breast cancer

5. Relapsed and refractory epithelial ovarian cancer

6. Metastatic castration-resistance prostate cancer

7. K-Ras wild type colorectal cancer (CRC)

8. K-Ras mutant CRC

9. 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.)

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.

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).

Related Conditions & MeSH terms

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

Intervention

Drug:
• STAR0602
solution, intravenous infusion

Locations

Country	Name	City	State
Canada	Princess Margaret Cancer Centre	Toronto	Ontario
United States	National Institutes of Health	Bethesda	Maryland
United States	Massachusetts General Hospital Cancer Center	Boston	Massachusetts
United States	Memorial Sloan-Kettering Cancer Center	New York	New York

Sponsors (1)

Lead Sponsor	Collaborator
Marengo Therapeutics, Inc.

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Phase 1 (Dose Escalation):Number of Participants with Dose-limiting Toxicities (DLTs) in Cycle 1		Cycle 1 (Cycle length= 28 days)
Primary	Phase 1 and 2 (Dose Escalation and Expansion): Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)		Up to 3 years
Primary	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	Phase 1 and 2 (Dose Escalation and Expansion): Percentage of Participants with ORR		Up to 3 years
Secondary	Phase 1 and 2 (Dose Escalation and Expansion): Duration of Responses (DOR)		Up to 3 years
Secondary	Phase 1 and 2 (Dose Escalation and Expansion): Percentage of Participants with Disease Control (CR, PR, and Stable Disease)		Up to 3 years
Secondary	Phase 2 (Dose Expansion): Progression Free Survival (PFS)		Up to 3 years
Secondary	Phase 2 (Dose Expansion): Overall Survival (OS)		Up to 3 years
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)