A Phase I/II, 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)
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Study Summary
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.
To evaluate the safety, tolerability, and preliminary clinical activity of STAR0602 as a single agent in patients with advanced antigen-rich solid tumors including PD-1 refractory and rare tumors.
To evaluate the activity of STAR0602 monotherapy in checkpoint inhibitor refractory advanced solid tumors
To evaluate the safety and clinical activity of STAR0602 as monotherapy in a biomarker-enriched cohort of patients with PD-1 refractory advanced solid tumors.
To address high unmet clinical needs in patients for whom PD-1 therapies are no longer effective.
To evaluate STAR0602 in well-defined populations will allow us to efficiently investigate biological and clinical activity.
To investigate the safety and efficacy of STAR0602 in patients with CPI-resistant cancers.
To determine a recommended Phase 2 dose (RP2D), based on safety and tolerability, pharmacokinetics, pharmacodynamics, and preliminary anti-tumor activity
To evaluate invikafusp as monotherapy in patients with anti-PD(L)1-resistant, antigen-rich solid tumors (TMB-H, MSI-H/dMMR, or virally associated).
To report: 1) updated clinical results of the completed dose escalation of intravenous invikafusp, Q2W, per 3+3 design with backfill at optimal biological dose (OBD) levels; 2) first report on RP2D determination based on PK, PD, safety and anti-tumor activity; 3) new results of translational immunology studies.
To evaluate the safety, tolerability, and preliminary efficacy of invikafusp alfa as a monotherapy in biomarker-selected patients with advanced antigen-rich solid tumors, including PD-1 refractory and rare tumor types. The trial consists of two parts: Phase 1 dose escalation and Phase 2 dose expansion.
- 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.
- 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
- CRC (both Ras wild type and mutant)
- Virally associated tumors
- Metastatic triple negative breast cancer
- Platinum-resistant epithelial ovarian cancer
- Metastatic castration-resistance prostate cancer
- Primary stage IV or recurrent non-small cell lung cancer
- Immunogenic solid tumors
- (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.
- patients who have the following solid tumors: 1) tissue-agnostic, TMB-H; 2) tissue-agnostic, dMMR/MSI-H; 3) CRC (both Ras wild-type and mutant) TMB-H and/or MSI-H/dMMR); 4) virally associated tumors such as Merkel cell carcinoma, cervical, oropharyngeal, anal, penile, vaginal, and vulvar cancers, or EBV-related solid tumors; 5) metastatic triple-negative breast cancer; 6) platinum-resistant epithelial ovarian cancer; 7) metastatic castration-resistant prostate cancer; 8) primary stage IV or recurrent non-small cell lung cancer; and 9) immunogenic tumors (e.g., cSCC, melanoma and RCC).
- Major Eligibility criteria: ≤ 3 lines of prior cancer therapies [anti-PD(L)-1s allowed] for advanced or metastatic disease; intolerance to standard therapies including anti-PD(L)-1s allowed; no liver metastases or adequately treated liver metastases either locally (e.g., by surgery, radiofrequency ablation, or chemoembolization) or systemically and stable for 3 months.
- Key Inclusion Criteria
- Age ≥18 years old.
- ECOG performance status of ≤ 1
- Measurable disease as per RECIST v1.1 criteria and documented by CT and/or MRI
- Life expectancy > 12 weeks.
- 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).
- 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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