RECRUITING

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

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

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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.

Official Title

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

Quick Facts

Study Start:2021-08-06

Study Completion:2025-12-31

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT04787042

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion 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 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 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).	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 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

Inclusion Criteria

Exclusion 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
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
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).

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
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

Contacts and Locations

Study Contact

Beatrice McQueen, Ph.D.

CONTACT

805-300-3912

beatrice@simchatherapeutics.com

Principal Investigator

Jeremy Barton, MD

STUDY_DIRECTOR

Simcha IL-18, Inc.

Study Locations (Sites)

HonorHealth Research Institute

Scottsdale, Arizona, 85258

United States

Sarah Cannon Research Institute at HealthONE

Denver, Colorado, 80218

United States

Yale Cancer Center

New Haven, Connecticut, 06519

United States

Moffitt Cancer Center

Tampa, Florida, 33612

United States

Massachusetts General Hospital

Boston, Massachusetts, 02114

United States

Roswell Park Cancer Institute

Buffalo, New York, 14263

United States

Collaborators and Investigators

Sponsor: Simcha IL-18, Inc.

Jeremy Barton, MD, STUDY_DIRECTOR, Simcha IL-18, Inc.

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2021-08-06

Study Completion Date2025-12-31

Study Record Updates

Study Start Date2021-08-06

Study Completion Date2025-12-31

Terms related to this study

Additional Relevant MeSH Terms

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