Phase 1a and Phase 2 Study for Safety, Preliminary Efficacy, PK and PD of ST-067

NCT04787042 | Recruiting Phase 1 DMC FDA Drug

• 3 other identifiers: ST-067-001KEYNOTE-E64MK-3475-E64
• Study Type: interventional
• Target: 316
• Locations: 1 country
• Sites: 6

Brief 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.

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; MSI-High

Outcome Measures

Primary Outcomes (4)

• Determine the maximum tolerated dose of ST-067 in phase 1a monotherapy

  Patients will be enrolled at a dose level that is predicted to be the MTD

  Day 29

• Evaluate the overall safety and tolerability of ST-067 in combination with pembrolizumab

  In patients experiencing insufficient response to a checkpoint inhibitor (PD-1) therapy administered alone or in combination.

  Day 29

• Number of Participants With Treatment-Related Adverse Events

  AE assessed by CTCAE 5.0

  Day 29

• Initial assessment of efficacy in phase 2

  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

  At 8 weeks

Secondary Outcomes (2)

• PK

  Day 29

• ADA

  Day 29

Study Arms (4)

Phase 1a, Dose Escalation

EXPERIMENTAL

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.

Biological: ST-067

Phase 2, Expansion

EXPERIMENTAL

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

Phase 1a, Dose Escalation, ST-067 SC + Obinutuzumab Pre-treatment

EXPERIMENTAL

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.

Biological: ST-067; Biological: Obinutuzumab 25 MG/1 ML Intravenous Solution [GAZYVA]

Phase 1 combination therapy

EXPERIMENTAL

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.

Biological: ST-067; Biological: pembrolizumab

Interventions

ST-067 BIOLOGICAL

ST-067 is an engineered variant of human interleukin-18.

Phase 1 combination therapy; Phase 1a, Dose Escalation; Phase 1a, Dose Escalation, ST-067 SC + Obinutuzumab Pre-treatment; Phase 2, Expansion

Obinutuzumab 25 MG/1 ML Intravenous Solution [GAZYVA] BIOLOGICAL

Obinutuzumab is a humanized anti-CD20 monoclonal antibody of the IgG1 subclass. It recognizes a specific epitope of the CD20 molecule found on B-cells.

Also known as: GAZYVA

Phase 1a, Dose Escalation, ST-067 SC + Obinutuzumab Pre-treatment

pembrolizumab BIOLOGICAL

Pembrolizumab is a potent humanized immunoglobulin G4 monoclonal antibody.

Also known as: KEYTRUDA®

Phase 1 combination therapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• History of another malignancy
• Known symptomatic brain metastases requiring \>10 mg/day of prednisolone or equivalent
• 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
• Any degree of respiratory compromise (from either malignant or non-malignant disease)
• Evidence of an ongoing systemic bacterial, fungal, or viral infection
• Has received a live vaccine within 30 days
• Major surgery within 4 weeks
• 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 systemic or enteric corticosteroids.
• Treatment with an approved, systemic anticancer therapy or an investigational agent within 4 weeks of Day 1
• 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
• Subjects with adrenal insufficiency
• Subjects with any chemistry or hematology laboratory values that are ≥Grade 2

Sponsors & Collaborators

• Simcha IL-18, Inc.: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (6)

HonorHealth Research Institute

Scottsdale, Arizona, 85258, United States

RECRUITING

Sarah Cannon Research Institute at HealthONE

Denver, Colorado, 80218, United States

RECRUITING

Yale Cancer Center

New Haven, Connecticut, 06519, United States

RECRUITING

Moffitt Cancer Center

Tampa, Florida, 33612, United States

RECRUITING

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

RECRUITING

Roswell Park Cancer Institute

Buffalo, New York, 14263, United States

RECRUITING

MeSH Terms

Conditions

Neoplasms; Melanoma; Carcinoma, Renal Cell; Triple Negative Breast Neoplasms; Carcinoma, Non-Small-Cell Lung; Squamous Cell Carcinoma of Head and Neck; Carcinoma

Interventions

obinutuzumab; pembrolizumab

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases; Breast Neoplasms; Breast Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases; Carcinoma, Squamous Cell; Head and Neck Neoplasms

Study Officials

• Jeremy Barton, MD

  Simcha IL-18, Inc.

  STUDY DIRECTOR

Central Study Contacts

Beatrice McQueen, Ph.D.

CONTACT

805-300-3912; beatrice@simchatherapeutics.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Dose escalation and expansion

Study Record Dates

• First Submitted: February 16, 2021
• First Posted: March 8, 2021
• Study Start: August 6, 2021
• Primary Completion: June 30, 2025
• Study Completion: December 31, 2025
• Last Updated: November 15, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (6)