Actively Recruiting
First-In-Human Phase 1/2 Study of ST-067 Alone, with Obinutuzumab, and with Pembrolizumab in Advanced Solid Tumors
Led by Simcha IL-18, Inc. · Updated on 2024-11-15
316
Participants Needed
6
Research Sites
26 weeks
Total Duration
On this page
Sponsors
S
Simcha IL-18, Inc.
Lead Sponsor
M
Merck Sharp & Dohme LLC
Collaborating Sponsor
AI-Summary
What this Trial Is About
Researchers are studying ST-067, an engineered variant of human interleukin-18, in patients with advanced solid tumors that have returned or not responded to prior treatments. This study includes a Phase 1a dose escalation to find the safest and most effective dose of ST-067 given by subcutaneous or intravenous routes, alone or with obinutuzumab pre-treatment or combined with pembrolizumab. The Phase 2 part will assess the preliminary effectiveness of ST-067 at the recommended dose in various cancers such as melanoma, renal cell carcinoma, triple-negative breast cancer, non-small cell lung cancer, head and neck squamous cell carcinoma, and MSI-High tumors. In Phase 1a, patients receive weekly doses of ST-067 starting at 30 µg/kg subcutaneously or 60 µg/kg intravenously, with dose levels adjusted based on safety findings. Some patients get obinutuzumab intravenously as a pre-treatment before ST-067 or receive ST-067 combined with pembrolizumab every three weeks. The dose limiting toxicity period is 28 days after the first ST-067 dose. Phase 2 will treat patients weekly with ST-067 at the recommended dose determined in Phase 1, focusing on specific tumor types. Participants will be closely monitored for safety, side effects, and how their cancer responds to treatment by assessing measurable tumor lesions every 8 to 12 weeks using RECIST 1.1 criteria. Blood samples will be collected to study how the drug behaves in the body and immune responses. The study team will evaluate maximum tolerated dose, safety, tolerability, and initial effectiveness. The entire study includes ongoing safety assessments and could continue until the end of 2025.
CONDITIONS
Brief Title
Phase 1a and Phase 2 Study for Safety, Preliminary Efficacy, PK and PD of ST-067
Who Can Participate
Eligibility Criteria
You may qualify if you...
- Male and female patients aged 18 years or older
- Provide written informed consent and authorizations as required
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- Histologically or cytologically confirmed diagnosis of advanced or metastatic solid tumor
- For Phase 1a, eligible tumors include melanoma, Merkel cell, renal cell carcinoma, urothelial, non-small cell lung cancer, triple negative breast cancer, squamous cell carcinoma of the head and neck, microsatellite instability-high, high tumor mutation burden, mismatch repair deficient, gastric, cervical, endometrial, cutaneous squamous, small cell lung, esophageal, hepatocellular carcinoma, and platinum resistant ovarian cancer
- Disease progression through standard therapy or standard therapy unavailable or unsuitable
- For Phase 1 combination therapy, additional eligible tumors include those listed for Phase 1a with specified genetic mutation exclusions
- For Phase 2, eligible tumors include 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
- At least one measurable lesion per RECIST 1.1 criteria not previously biopsied or irradiated
- Accessible tumor for mandatory biopsy before and during treatment
You will not qualify if you...
- History of another malignancy
- Symptomatic brain metastases requiring more than 10 mg/day prednisolone or equivalent
- Significant cardiovascular disease within 6 months prior to treatment
- Significant ECG abnormalities for Phase 1a and 2 monotherapy
- Any degree of respiratory compromise
- Ongoing systemic bacterial, fungal, or viral infection
- Live vaccine within 30 days prior to treatment
- Major surgery within 4 weeks prior to treatment
- Prior solid organ or bone marrow progenitor cell transplantation
- Prior high dose chemotherapy requiring stem cell rescue
- History of active autoimmune disorders
- Ongoing immunosuppressive therapy including corticosteroids
- Treatment with anticancer therapy or investigational agents within 4 weeks of Day 1
- Positive SARS-CoV-2 viral test within 28 days prior to dosing without clinical recovery
- Adrenal insufficiency
- Chemistry or hematology laboratory values of Grade 2 or higher
- For Phase 1 combination therapy: active CNS metastases or carcinomatous meningitis unless stable and steroid-free
- Prior radiotherapy within 2 weeks or history of radiation pneumonitis
- Active autoimmune disease requiring systemic treatment in past 2 years
- Prior therapy with certain immune checkpoint inhibitors discontinued due to severe immune-related adverse events
- Severe hypersensitivity to pembrolizumab or its excipients
- History or current pneumonitis/interstitial lung disease requiring steroids
- Radiation therapy to the lung exceeding 30Gy within 6 months before study treatment
AI-Screening
AI-Powered Screening
Complete this quick 3-step screening to check your eligibility
Your Study Journey
Duration - 2 to 4 weeks
Participants are screened for eligibility to participate in the trial.
1 visit (in-person)
Duration - At least 7 days
Participants receive obinutuzumab pre-treatment administered intravenously on 2 consecutive days, starting at least 7 days before the first ST-067 dose.
2 visits (in-person) for obinutuzumab infusions
Duration - Treatment continues with weekly ST-067 dosing; dose-limiting toxicity period is 28 days. Treatment duration varies by cohort and phase.
Participants receive weekly doses of ST-067 alone or in combination with obinutuzumab and/or pembrolizumab. Pembrolizumab is given every 3 weeks in combination therapy. The treatment aims to determine the maximum tolerated dose and evaluate preliminary efficacy.
Weekly visits for ST-067 dosing; pembrolizumab every 3 weeks if combined
Duration - Up to study completion (through 2025-12-31)
Participants are monitored for safety and tumor response with assessments approximately every 8 to 12 weeks using RECIST 1.1 criteria.
Visits every 8 to 12 weeks for tumor assessment
Trial Site Locations
Total: 6 locations
1
HonorHealth Research Institute
Scottsdale, Arizona, United States, 85258
Actively Recruiting
2
Sarah Cannon Research Institute at HealthONE
Denver, Colorado, United States, 80218
Actively Recruiting
3
Yale Cancer Center
New Haven, Connecticut, United States, 06519
Actively Recruiting
4
Moffitt Cancer Center
Tampa, Florida, United States, 33612
Actively Recruiting
5
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
Actively Recruiting
6
Roswell Park Cancer Institute
Buffalo, New York, United States, 14263
Actively Recruiting
Research Team
B
Beatrice McQueen, Ph.D.
How is the study designed?
Study Type
INTERVENTIONAL
Masking
NONE
Allocation
NON_RANDOMIZED
Model
SEQUENTIAL
Primary Purpose
TREATMENT
Number of Arms
4
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