Phase 1a and Phase 2 Study for PK, PD, Safety and Preliminary Efficacy of ST-067
Study Details
Study Description
Brief Summary
This is a multicenter Phase 1a open-label, dose escalation study, and a Phase 2 study of ST-067. Phase 1a is a first-in-human (FIH) dose escalation study in patients aged 18 years or older diagnosed with solid tumors who have exhausted available standard. Phase 2 will enroll patients aged 18 years or older diagnosed with the following solid tumors: melanoma, renal cell carcinoma, triple negative breast cancer, non-small cell lung cancer, squamous cell carcinoma of the head and neck, and microsatellite instability-high tumors.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1/Phase 2 |
Detailed Description
Phase 1a is designed to determine the recommended Phase 2 dose of ST-067 monotherapy using a modified toxicity probability interval (mTPI) design. ST-067 is administered as subcutaneous injection once weekly. Pre and on treatment biopsies will be mandated for all patients. There will be evaluation of PK and PD effects.
Phase 2 will evaluate the preliminary efficacy of ST-067 administered at the RP2D to patients with the following tumor types. A Simon 2 stage design is used to calculate the sample size and early stopping rules will be employed in the event of lack of efficacy in any of the cohorts. RECIST 1.1 will be used to assess tumor response every 8-12 weeks.
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Melanoma (n=28)
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Renal cell carcinoma (n=25)
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Triple-negative best cancer (n=25)
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Non-small cell lung cancer (n=25)
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squamous cell carcinoma of the head and neck (n=28)
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MSI-Hi tumors (n=25)
Safety will be assessed for each patient throughout the study.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Phase 1a, Dose Escalation In phase 1 dose escalation will start at a dose level of 30ug/kg . Patients will be treated every week and the DLT evaluation period is 28 days. According to the mTPI schema initially there will be 2 patients per cohort until the first DLT is observed at which point cohorts will be expanded according to the predetermined mTPI design. Up to 12 patients will be treated at the RP2D |
Biological: ST-067
ST-067 is an engineered variant of human interleukin-18.
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| Experimental: Phase 2, Expansion Phase 2 will enroll patients aged 18 years or older diagnosed with the following solid tumors: melanoma, renal cell carcinoma (RCC), triple negative breast cancer (TNBC), non-small cell lung cancer (NSCLC), squamous cell carcinoma of the head and neck (SCCHN), and microsatellite instability-high (MSI-Hi) tumors at the RP2D. |
Biological: ST-067
ST-067 is an engineered variant of human interleukin-18.
|
Outcome Measures
Primary Outcome Measures
- Determine the maximum tolerated dose of ST-067 in phase 1a [Day 29]
6 to 12 patients have been enrolled at a dose level that is predicted to be the MTD
- Initial assessment of efficacy in phase 2 [At 8 weeks]
Investigator-assessed ORR, defined as either a complete response (CR) or partial response (PR) by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 based on computed tomography (CT) or magnetic resonance imaging (MRI) scans
- Number of Participants With Treatment-Related Adverse Events [Day 29]
AE assessed by CTCAE 5.0
Secondary Outcome Measures
- PK [Day 29]
Peak Plasma Concentration (Cmax)
- ADA [Day 29]
Incidence of ADA to ST-067
Eligibility Criteria
Criteria
Inclusion Criteria:
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Male and female patients aged ≥18 years
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Must provide written informed consent and any authorizations required by local law
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Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
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Have histologically or cytologically confirmed diagnosis of advanced/metastatic solid tumor
For Phase 1a, the following solid tumors are allowed: Melanoma, Merkel cell, RCC, urothelial, NSCLC,TNBC, SCCHN, microsatellite instability high, high tumor mutation burden (Hi TMB) or mismatch repair deficient, gastric, cervical, endometrial, cutaneous squamous, small cell lung, esophageal, hepatocellular carcinoma and platinum resistant ovarian cancer.
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For patients who have developed disease progression through standard therapy, or
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For patients whom standard of care therapy that prolongs survival is not available or suitable (according to the investigator and after consultation with the Medical Monitor)
For Phase 2, the following solid tumors are allowed:
Melanoma, RCC, TNBC, NSCLC, SCCHN, and MSI-Hi tumors
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Has at least 1 measurable lesion per RECIST 1.1 criteria which has not been biopsied or received prior irradiation
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Has an accessible tumor for biopsy pre- and on-treatment (mandatory).
Exclusion Criteria:
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History of another malignancy
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Known symptomatic brain metastases requiring >10 mg/day of prednisolone
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Significant cardiovascular disease
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Significant ECG abnormalities i
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Evidence of an ongoing systemic bacterial, fungal, or viral infection
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Has received a live vaccine within 30 days
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Major surgery within 4 weeks
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Prior solid organ or bone marrow progenitor cell transplantation
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Prior high dose chemotherapy requiring stem cell rescue
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History of active autoimmune disorders
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Ongoing immunosuppressive therapy, including systemic or enteric corticosteroids.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | HonorHealth Research Institute | Scottsdale | Arizona | United States | 85258 |
| 2 | Sarah Cannon Research Institute at HealthONE | Denver | Colorado | United States | 80218 |
| 3 | Yale Cancer Center | New Haven | Connecticut | United States | 06519 |
| 4 | Massachusetts General Hospital | Boston | Massachusetts | United States | 02114 |
| 5 | Roswell Park Cancer Institute | Buffalo | New York | United States | 14263 |
| 6 | Providence Cancer Institute Franz Clinic | Portland | Oregon | United States | 97213 |
Sponsors and Collaborators
- Simcha IL-18, Inc.
Investigators
- Study Director: Jeremy Barton, MD, Simcha IL-18, Inc.
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- ST-067-001