Clinical trial NCT05592626: A Study of a Selective T Cell Receptor (TCR) Targeting, Bifunctional Antibody-fusion Molecule STAR0602 in Participants With Advanced Solid Tumors
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)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Advanced Solid Tumors
Genital Neoplasm, Female
Urogenital Neoplasms
Lung Neoplasm
Neoplasms by Site
Papillomavirus Infection
Epstein-Barr Virus Infections
Carcinoma
Neoplasms
Vulvar Neoplasms
Vulvar Diseases
Abdominal Neoplasm
Keywords: 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
Lead sponsor: Marengo Therapeutics, Inc.
Sponsor class: INDUSTRY
First posted: 2022-10-24
Enrollment: 365
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.

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).

Eligibility criteria: 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.

Primary outcomes:
measure: Phase 1 (Dose Escalation):Number of Participants with Dose-limiting Toxicities (DLTs) in Cycle 1
timeFrame: Cycle 1 (Cycle length= 28 days)
measure: Phase 1 and 2 (Dose Escalation and Expansion): Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: Up to 3 years
measure: Phase 2 (Dose Expansion): Percentage of Participants with Overall Objective Tumor Responses (ORR)
timeFrame: Up to 3 years
Secondary outcomes:
measure: Phase 1 and 2 (Dose Escalation and Expansion): Percentage of Participants with ORR
timeFrame: Up to 3 years
measure: Phase 1 and 2 (Dose Escalation and Expansion): Duration of Responses (DOR)
timeFrame: Up to 3 years
measure: Phase 1 and 2 (Dose Escalation and Expansion): Percentage of Participants with Disease Control (CR, PR, and Stable Disease)
timeFrame: Up to 3 years
measure: Phase 2 (Dose Expansion): Progression Free Survival (PFS)
timeFrame: Up to 3 years
measure: Phase 2 (Dose Expansion): Overall Survival (OS)
timeFrame: Up to 3 years
measure: Phase 1 and 2 (Dose Escalation and Expansion): Maximum Observed Plasma Concentration (Cmax) for STAR0602
timeFrame: 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)
measure: Phase 1 and 2 (Dose Escalation and Expansion): Time (Tmax) to Reach the Maximum Plasma Concentration (Cmax) for STAR0602
timeFrame: 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)
measure: Phase 1 and 2 (Dose Escalation and Expansion): Area Under the Plasma Concentration (AUC) Versus Time Curve for STAR0602
timeFrame: 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)
measure: Phase 1 and 2 (Dose Escalation and Expansion): Terminal Elimination Half-life (t1/2) for STAR0602
timeFrame: 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)
measure: Phase 1 and 2 (Dose Escalation and Expansion): Apparent Total Body Clearance (CL) for STAR0602
timeFrame: 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)
measure: Phase 1 and 2 (Dose Escalation and Expansion): Apparent Volume of Distribution (Vd) for STAR0602
timeFrame: 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)
measure: Phase 1 and 2 (Dose Escalation and Expansion): Anti-drug Antibody (ADA) formation
timeFrame: Dose Escalation and Expansion: Day 1 of predetermined cycles up to 3 years (Cycle length= 28 days)
Other outcomes:
Locations:
city: Celebration
country: United States
facility: AdventHealth Celebration
state: Florida
city: Miami
country: United States
facility: University of Miami Sylvester Comprehensive Cancer Center
state: Florida
city: Bethesda
country: United States
facility: National Institutes of Health
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital Cancer Center
state: Massachusetts
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: Detroit
country: United States
facility: Karmanos Cancer Institute
state: Michigan
city: New York
country: United States
facility: Memorial Sloan-Kettering Cancer Center
state: New York
city: Columbus
country: United States
facility: The Ohio State University Comprehensive Cancer Center
state: Ohio
city: Toronto
country: Canada
facility: Princess Margaret Cancer Centre
state: Ontario
city: Bordeaux
country: France
facility: Institut Bergonié
city: Villejuif
country: France
facility: Institute Gustave Roussy
city: Barcelona
country: Spain
facility: Vall d'Hebron Institute of Oncology
state: Cataluna
city: Madrid
country: Spain
facility: START Madrid FJD
Study officials:
References: