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CancerPhase 1/2NCT04787042

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

A Phase 1/2 study testing ST-067, Obinutuzumab 25 MG/1 ML Intravenous Solution [GAZYVA] and pembrolizumab in people with Cancer and Solid Tumor, run by Simcha IL-18, Inc. at 6 sites in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Cancer, Solid Tumor, Melanoma
What is being tested?
ST-067, Obinutuzumab 25 MG/1 ML Intravenous Solution [GAZYVA] and pembrolizumab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
316 participants
Where
6 sitesUnited States
Study dates
6 Aug 2021to 31 Dec 2025
Phase
Phase 1/2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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).

Who cannot join

  • 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
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  • 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
  • Additional exclusion criteria for Phase 1 combination therapy only:
  • 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.
  • Prior radiotherapy within 2 weeks of start of study treatment or history of radiation pneumonitis.
  • 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.
  • 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
  • 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
  • History of (non-infectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease
  • Subjects that have received radiation therapy to the lung that is >30Gy within 6 months of the first dose of study treatment

Trial locations and contacts

6 sites in 1 country. Contact the study team or a site near you to ask about taking part.

Beatrice McQueen, Ph.D. contact

805-300-3912

beatrice@simchatherapeutics.com

6 sites in 1 country

United States6 sites, 6 recruiting

  • Massachusetts General Hospital

    Boston, Massachusetts, 02114

    Ryan Sullivan, MD

    Recruiting

  • Roswell Park Cancer Institute

    Buffalo, New York, 14263

    Igor Puzanov, MD

    Recruiting

  • Sarah Cannon Research Institute at HealthONE

    Denver, Colorado, 80218

    Gerald Falchook, MD, MS

    Recruiting

  • Yale Cancer Center

    New Haven, Connecticut, 06519

    Harriet Kluger, MD

    Recruiting

  • HonorHealth Research Institute

    Scottsdale, Arizona, 85258

    Justin Moser, MD

    Recruiting

  • Moffitt Cancer Center

    Tampa, Florida, 33612

    Ahmad Tarhini, MD

    Recruiting

Other trials in United States

About this study

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

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.

Read the detailed description

Phase 1a is designed to determine the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D) of ST067, administered by subcutaneous (SC) or intravenous (IV) dosing, in subjects with relapsed or refractory solid tumors, as well as to determine the MTD and recommended Phase 2 dose of ST067, administered SC with obinutuzumab (Gazyva®) as pretreatment in subjects with relapsed or refractory solid tumors using a modified toxicity probability interval (mTPI) design. There will be evaluations of ST-067 PK and PD effects.

Phase 2 will evaluate the preliminary efficacy of ST-067 administered at the RP2D to patients with the following tumor types. A Simon 2 stage design is used to calculate the sample size and early stopping rules will be employed in the event of lack of efficacy in any of the cohorts. RECIST 1.1 will be used to assess tumor response every 8-12 weeks.

  • Melanoma (n=28)
  • Renal cell carcinoma (n=25)
  • Triple-negative best cancer (n=25)
  • Non-small cell lung cancer (n=25)
  • squamous cell carcinoma of the head and neck (n=28)
  • MSI-Hi tumors (n=25)

A Simon 2 stage design is used to calculate the sample size and early stopping rules will be employed in the event of lack of efficacy in any of the cohorts. RECIST 1.1 will be used to assess tumor response every 8-12 weeks.

Safety will be assessed for each patient throughout the study.

Being tested
ST-067, Obinutuzumab 25 MG/1 ML Intravenous Solution [GAZYVA], pembrolizumab
Medical subject headings
Neoplasms, Melanoma, Carcinoma, Renal Cell, Triple Negative Breast Neoplasms, Carcinoma, Non-Small-Cell Lung, Squamous Cell Carcinoma of Head and Neck, Carcinoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • ST-067Biological

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

  • Obinutuzumab 25 MG/1 ML Intravenous Solution [GAZYVA]Biological

    Also called GAZYVA

    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.

  • pembrolizumabBiological

    Also called KEYTRUDA®

    Pembrolizumab is a potent humanized immunoglobulin G4 monoclonal antibody.

Study groups in NCT04787042
Study groupRoleWhat they receive
Phase 1a, Dose EscalationExperimentalIn 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.
Receives: Biological: ST-067
Phase 2, ExpansionExperimentalPhase 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.
Receives: Biological: ST-067
Phase 1a, Dose Escalation, ST-067 SC + Obinutuzumab Pre-treatmentExperimentalPatients 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.
Receives: Biological: ST-067; Biological: Obinutuzumab 25 MG/1 ML Intravenous Solution [GAZYVA]
Phase 1 combination therapyExperimentalPhase 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.
Receives: Biological: ST-067; Biological: pembrolizumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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

    Measured: Day 29

  2. 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.

    Measured: Day 29

  3. Number of Participants With Treatment-Related Adverse Events

    AE assessed by CTCAE 5.0

    Measured: Day 29

  4. 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

    Measured: At 8 weeks

Secondary outcomes (2)

  1. PK

    Peak Plasma Concentration (Cmax)

    Measured: Day 29

  2. ADA

    Incidence of ADA to ST-067

    Measured: Day 29

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted8 Mar 2021
  2. Study start6 Aug 2021
  3. Primary completion30 Jun 2025 (estimated)
  4. Study completion31 Dec 2025 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Model description
Dose escalation and expansion
Masking
None (open label)
Enrolment
316 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04787042
Sponsor's protocol ID
ST-067-001
Other IDs
KEYNOTE-E64, MK-3475-E64
Status last verified
Nov 2024
First submitted
16 Feb 2021
Last updated
15 Nov 2024
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing ST-067, Obinutuzumab 25 MG/1 ML Intravenous Solution [GAZYVA] and pembrolizumab in people with Cancer and Solid Tumor, run by Simcha IL-18, Inc. at 6 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 14 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 15 Nov 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 6 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Beatrice McQueen, Ph.D. (805-300-3912, beatrice@simchatherapeutics.com), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Determine the maximum tolerated dose of ST-067 in phase 1a monotherapy (time frame: Day 29). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04787042.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Nov 2024.

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Clinical Trial NCT04787042 | AzTrials