START-001: A Study of a Selective T Cell Receptor (TCR) Targeting, Bifunctional Antibody-fusion Molecule STAR0602 in Participants With Advanced Solid Tumors

Sponsor

Marengo Therapeutics, Inc. (Industry)

Overall Status

Recruiting

CT.gov ID

NCT05592626

Collaborator

(none)

365

Enrollment

Locations

Arms

44.9

Anticipated Duration (Months)

182.5

Patients Per Site

4.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Advanced Solid Tumor	Drug: STAR0602	Phase 1/Phase 2

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 Design

Study Type:

Interventional

Anticipated Enrollment :

365 participants

Allocation:

Non-Randomized

Intervention Model:

Sequential Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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)

Actual Study Start Date :

Jan 4, 2023

Anticipated Primary Completion Date :

Oct 1, 2026

Anticipated Study Completion Date :

Oct 1, 2026

Arms and Interventions

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

Arm

Intervention/Treatment

Experimental: Phase 1: Advanced Solid Tumors

Dose Escalation; Intervention: Drug: STAR0602

Drug: STAR0602

solution, intravenous infusion

Experimental: Phase 2: Advanced Solid Tumors

Dose Expansion; Recommended Phase 2 Dose (RP2D) identified from Phase 1 will be used in Phase 2; Intervention: Drug: STAR0602

Drug: STAR0602

solution, intravenous infusion

Outcome Measures

Primary Outcome Measures

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

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)]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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).