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

Marengo Therapeutics

Status and phase: Enrolling; Phase 2; Phase 1

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

Treatments: Drug: STAR0602

Study type: Interventional

Funder types: Industry

Identifiers

NCT05592626

CP-START-001

Details and patient eligibility

About

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.

Full 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).

Enrollment: 365 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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365 participants in 2 patient groups

Phase 1: Advanced Solid Tumors

Experimental group

Description:

Dose Escalation; Intervention: Drug: STAR0602

Treatment:

Drug: STAR0602

Phase 2: Advanced Solid Tumors

Experimental group

Description:

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

Treatment:

Drug: STAR0602