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

Who is this study for? Patients with Cancer
What treatments are being studied? ST-067
Status: Recruiting
Location: See all (6) locations...
Intervention Type: Biological
Study Type: Interventional
Study Phase: Phase 1/Phase 2
SUMMARY

This is a multiphase, multicenter study, which includes a Phase 1a open-label, dose escalation monotherapy study of ST-067 given as an SC injection with or without obinutuzumab \[Gazyva®\] pre-treatment, by IV infusion, and in combination with pembrolizumab. A Phase 2 monotherapy arm is also planned; the exact design of the Phase 2 study elements with respect to formulation and pre-treatment will be determined after completion of the Phase 1 study portion of the trial.

Eligibility
Participation Requirements
Sex: All
Minimum Age: 18
Healthy Volunteers: f
View:

• Male and female patients aged ≥18 years

• Must provide written informed consent and any authorizations required by local law

• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

• 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.

⁃ For patients who have developed disease progression through standard therapy, or

⁃ 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

• Has at least 1 measurable lesion per RECIST 1.1 criteria which has not been biopsied or received prior irradiation

• Has an accessible tumor for biopsy pre- and on-treatment (mandatory).

Locations
United States
Arizona
HonorHealth Research Institute
RECRUITING
Scottsdale
Colorado
Sarah Cannon Research Institute at HealthONE
RECRUITING
Denver
Connecticut
Yale Cancer Center
RECRUITING
New Haven
Florida
Moffitt Cancer Center
RECRUITING
Tampa
Massachusetts
Massachusetts General Hospital
RECRUITING
Boston
New York
Roswell Park Cancer Institute
RECRUITING
Buffalo
Contact Information
Primary
Beatrice McQueen, Ph.D.
beatrice@simchatherapeutics.com
805-300-3912
Time Frame
Start Date: 2021-08-06
Estimated Completion Date: 2025-12-31
Participants
Target number of participants: 316
Treatments
Experimental: Phase 1a, Dose Escalation
In the Phase 1a monotherapy study, the starting dose of ST-067 will be 30 μg/kg, with a total of 7 dose level cohorts planned.~The starting dose for the IV infusion monotherapy dosing will be 60 µg/kg.~Patients will be treated every week with ST-067 in all cohorts. The DLT period is 28 days after the initial dose of ST-067. According to the mTPI schema initially there will be 3 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.
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.
Experimental: Phase 1a, Dose Escalation, ST-067 SC + Obinutuzumab Pre-treatment
Patients will be treated every week with ST-067 in all cohorts. The DLT period is 28 days after the initial dose of ST-067. According to the mTPI schema initially there will be 3 patients per cohort until the first DLT is observed at which point cohorts will be expanded according to the predetermined mTPI design.~The starting dose for ST-067 with obinutuzumab pre-treatment will be 120µg/kg. Obinutuzumab will be administered at 1000 mg daily via IV infusion on 2 consecutive days, with the first dose given at least 7 days prior to first dose of SC ST-067.
Experimental: Phase 1 combination therapy
Phase 1 dose escalation in combination with pembrolizumab will start at a dose of 30 µg/kg of ST-067 and 200 mg every 3 weeks of pembrolizumab. Patients will be treated every week with ST-067 and every three weeks with pembrolizumab. The MTD will be determined based on the mTPI design.
Sponsors
Collaborators: Merck Sharp & Dohme LLC
Leads: Simcha IL-18, Inc.

This content was sourced from clinicaltrials.gov

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