Evaluating the safety and effectiveness of ST-067 in treating various solid tumors

A First-In-Human Phase 1/2 Open-Label Study of Intravenous ST-067, Subcutaneous ST-067 with or Without Obinutuzumab Pre-Treatment, and ST-067 in Combination with Pembrolizumab in Subjects with Advanced Solid Malignancies

This study is testing a new treatment called ST-067 to see if it can help people with tough-to-treat solid tumors feel better and improve their health.

Quick facts

• Phase: PHASE1; PHASE2
• Study type: Interventional
• Enrollment: 316 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Simcha IL-18, Inc. (industry)
• Drugs / interventions: pembrolizumab, chemotherapy, radiation, obinutuzumab
• Locations: 6 sites (Scottsdale, Arizona and 5 other locations)
• Trial ID: NCT04787042 on ClinicalTrials.gov

What this trial studies

This clinical trial is a multiphase, multicenter investigation focusing on the safety and preliminary efficacy of ST-067, a new treatment for patients with relapsed or refractory solid tumors. The study consists of a Phase 1a open-label dose escalation to determine the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D) of ST-067, administered either subcutaneously or intravenously, with or without obinutuzumab pre-treatment. Following this, a Phase 2 arm will assess the efficacy of ST-067 in specific tumor types, utilizing a Simon 2 stage design for sample size calculation and early stopping rules based on efficacy outcomes. Tumor responses will be evaluated using RECIST 1.1 criteria every 8-12 weeks.

Who should consider this trial

Good fit: Ideal candidates include adults aged 18 and older with advanced or metastatic solid tumors who have progressed through standard therapies or for whom such therapies are unsuitable.

Not a fit: Patients with early-stage tumors or those who have not yet undergone standard treatment options may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients with advanced solid tumors that are resistant to standard therapies.

How similar studies have performed: Other studies have shown promise with similar immunotherapy approaches, suggesting potential for success in this novel treatment.

Eligibility criteria

Inclusion Criteria:

1. Male and female patients aged ≥18 years
2. Must provide written informed consent and any authorizations required by local law
3. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
4. 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.
   1. For patients who have developed disease progression through standard therapy, or
   2. For patients whom standard of care therapy that prolongs survival is unavailable or unsuitable (according to the investigator and after consultation with the Medical Monitor) For Phase 1 combination therapy dose escalation, the following solid tumors are allowed: Melanoma, Merkel cell, RCC, urothelial, NSCLC (with no EGFR, TRK receptor, or ALK positive mutations/fusions), TNBC, SCCHN, MSI-Hi tumors, Hi TMB or mismatch repair deficient, gastric, cervical, endometrial, cutaneous squamous, small cell lung, esophageal, and HCC

      * TNBC is diagnosed in a tumor which does not express estrogen receptor or progesterone receptor, is not human epidermal growth factor receptor 2 (HER2) 3+ on IHC or is negative by fluorescence in situ hybridization (FISH).
      * MSI high tumor should have mutations in 30% or more microsatellites by PCR or be negative for MSH1/2/6 or PMS-2 by IHC.
      * Hi-TMB high tumor has 10 mut/Mb or greater calculated from whole genome sequencing or whole exome sequencing

   For Phase 2, the following solid tumors are allowed:

   Melanoma, RCC, TNBC, NSCLC, SCCHN, and MSI-Hi tumors
5. Has at least 1 measurable lesion per RECIST 1.1 criteria which has not been biopsied or received prior irradiation
6. Has an accessible tumor for biopsy pre- and on-treatment (mandatory).

Exclusion Criteria:

1. History of another malignancy
2. Known symptomatic brain metastases requiring \>10 mg/day of prednisolone or equivalent
3. Significant cardiovascular disease (MI, thrombotic events,) within 6 months prior to study treatmentSignificant ECG abnormalities (Phase 1a and 2 monotherapy only) including unstable cardiac arrhythmia requiring medication, second-degree atrioventricular block type II, third degree AV
4. Any degree of respiratory compromise (from either malignant or non-malignant disease)
5. Evidence of an ongoing systemic bacterial, fungal, or viral infection
6. Has received a live vaccine within 30 days
7. Major surgery within 4 weeks
8. Prior solid organ or bone marrow progenitor cell transplantation
9. Prior high dose chemotherapy requiring stem cell rescue
10. History of active autoimmune disorders
11. Ongoing immunosuppressive therapy, including systemic or enteric corticosteroids.
12. Treatment with an approved, systemic anticancer therapy or an investigational agent within 4 weeks of Day 1
13. A positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral test within 28 days prior to dosing, unless there is Investigator-confirmed clinical recovery on or before C1D1
14. Subjects with adrenal insufficiency
15. Subjects with any chemistry or hematology laboratory values that are ≥Grade 2

    Additional exclusion criteria for Phase 1 combination therapy only:
16. Presence of known active CNS metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are radiologically stable, i.e., without evidence of progression for at least 4 weeks by repeat imaging, clinically stable, and without requirement of steroid treatment for at least 14 days prior to first dose of study treatment.
17. Prior radiotherapy within 2 weeks of start of study treatment or history of radiation pneumonitis.
18. Presence of an active documented autoimmune disease that has required systemic treatment in the past 2 years (i.e., with use of disease modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (e.g., thyroxine or insulin) is not considered a form of systemic treatment and is allowed. Subjects may use topical and/or inhaled corticosteroids. However, subjects with adrenal insufficiency on replacement doses of steroids are not allowed.
19. Prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g., CTLA-4, OX40, CD137), and was discontinued from that treatment due to a Grade 3 or higher irAE
20. Severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients. Subjects who have been retreated after such a reaction may be allowed after discussion with the Simcha Medical Monitor
21. History of (non-infectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease
22. Subjects that have received radiation therapy to the lung that is \>30Gy within 6 months of the first dose of study treatment

Where this trial is running

Scottsdale, Arizona and 5 other locations

• HonorHealth Research Institute — Scottsdale, Arizona, United States (RECRUITING)
• Sarah Cannon Research Institute at HealthONE — Denver, Colorado, United States (RECRUITING)
• Yale Cancer Center — New Haven, Connecticut, United States (RECRUITING)
• Moffitt Cancer Center — Tampa, Florida, United States (RECRUITING)
• Massachusetts General Hospital — Boston, Massachusetts, United States (RECRUITING)
• Roswell Park Cancer Institute — Buffalo, New York, United States (RECRUITING)

Study contacts

• Study coordinator: Beatrice McQueen, Ph.D.

Conditions: Cancer, Solid Tumor, Melanoma, Renal Cell Carcinoma, Triple-negative Breast Cancer, Non Small Cell Lung Cancer, Squamous Cell Carcinoma of the Head and Neck, Carcinoma