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

This is an interventional treatment trial for Advanced Solid Tumors focused on measuring 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 Read More

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).