ST-067-001 for Solid Tumors

Recruiting at 6 trial locations

Overseen By Beatrice McQueen, Ph.D.

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Simcha IL-18, Inc.

Must not be taking: Immunosuppressants, Corticosteroids

Disqualifiers: Autoimmune disorders, Brain metastases, Cardiovascular disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 75

316 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called ST-067 (Decoy-Resistant IL-18) to evaluate its safety and effectiveness for people with advanced cancers such as melanoma and lung cancer. Researchers aim to determine the optimal dose and assess its performance both alone and in combination with other drugs like pembrolizumab, a type of immunotherapy. Suitable candidates for this trial include those diagnosed with advanced solid tumors unresponsive to standard treatments. As a Phase 1, Phase 2 trial, it focuses on understanding the treatment's effects in people and measuring its initial effectiveness, offering patients an opportunity to contribute to groundbreaking cancer research.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot participate if you are on ongoing immunosuppressive therapy or have received systemic anticancer therapy within 4 weeks of starting the trial.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that ST-067 is a promising treatment currently undergoing safety testing in humans. Researchers are studying it both alone and with other immune therapies like pembrolizumab. Earlier lab studies demonstrated that ST-067, a modified version of interleukin-18 that boosts the immune system, enhanced the immune response without being easily blocked by other proteins. This suggests potential effectiveness in fighting tumors.

When combined with pembrolizumab, an approved treatment for various cancers, researchers are monitoring for side effects. Pembrolizumab's approval provides some reassurance about its safety, but the combination with ST-067 remains under study.

For patients receiving ST-067 alone or with pre-treatment using obinutuzumab (another immune-targeting drug), trials are closely monitoring safety. Early animal studies showed that similar treatments could be harmful in large doses but were better tolerated when administered correctly.

As these treatments are in early research stages, the main focus is determining the safest dosages. Safety checks are ongoing, and researchers are closely watching for any potential side effects to ensure patient safety. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about ST-067 because it offers a novel approach to treating advanced cancers by combining with immunotherapies like pembrolizumab and obinutuzumab. Unlike traditional treatments such as chemotherapy and radiation, which directly target and kill cancer cells, ST-067 boosts the body's immune response to attack the cancer. This treatment is particularly promising because it targets multiple types of solid tumors, including melanoma and non-small cell lung cancer, with a potentially more tailored and less toxic approach. By enhancing the immune system's ability to fight cancer, ST-067 could improve outcomes for patients with difficult-to-treat cancers.

What evidence suggests that this trial's treatments could be effective for advanced cancers?

Research shows that ST-067 could be a promising treatment for advanced cancers. ST-067 is a modified version of a protein called IL-18, which helps the immune system fight cancer. This version is unique because it can function even when IL-18BP, a blocker, tries to inhibit it. Animal studies have shown that ST-067 can slow tumor growth without causing major side effects. In this trial, some participants will receive ST-067 with pembrolizumab, potentially enhancing the immune system's attack on tumors. Others will receive ST-067 with obinutuzumab, another cancer treatment, which early evidence suggests could increase its effectiveness. ^{1 4 6 7 8}

Who Is on the Research Team?

Jeremy Barton, MD

Principal Investigator

Simcha IL-18, Inc.

Are You a Good Fit for This Trial?

Adults (≥18 years) with advanced or metastatic cancer, including melanoma and lung cancer, who've progressed after standard therapy or for whom no survival-prolonging standard care is available. Participants must be able to perform light work (ECOG status of 0 or 1), have at least one measurable lesion not previously treated by biopsy or radiation, and an accessible tumor for required biopsies.

Inclusion Criteria

My cancer is one of the following types: melanoma, kidney, triple-negative breast, non-small cell lung, head and neck, or has high microsatellite instability.

My condition worsened despite standard treatments.

My tumor has not been biopsied or treated with radiation.

Exclusion Criteria

I do not have serious heart, breathing, adrenal gland, or autoimmune conditions.

I have not had radiation therapy in the past two weeks.

I do not have serious heart, lung, immune system, or adrenal gland problems.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase 1a Dose Escalation

Determine the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D) of ST-067, administered by subcutaneous (SC) or intravenous (IV) dosing, with or without obinutuzumab pre-treatment.

28 days per cohort

Weekly visits for dosing

Phase 1 Combination Therapy

Dose escalation in combination with pembrolizumab to determine MTD using mTPI design.

28 days per cohort

Weekly visits for ST-067, every 3 weeks for pembrolizumab

Phase 2 Expansion

Evaluate the preliminary efficacy of ST-067 administered at the RP2D in various solid tumors using a Simon 2 stage design.

8-12 weeks per assessment

Tumor response assessment every 8-12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• ST-067

Trial Overview The trial tests ST-067 as a subcutaneous injection alone and in combination with IV infusion obinutuzumab (Gazyva®) plus pembrolizumab (Keytruda). It's a multi-phase study starting with dose escalation to assess safety and preliminary effectiveness before moving on to Phase 2.

How Is the Trial Designed?

Group I: Phase 2, Expansion Experimental Treatment 1 Intervention

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.

Group II: Phase 1a, Dose Escalation, ST-067 SC + Obinutuzumab Pre-treatment Experimental Treatment 2 Interventions

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.

Group III: Phase 1a, Dose Escalation Experimental Treatment 1 Intervention

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.

Group IV: Phase 1 combination therapy Experimental Treatment 2 Interventions

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.

Who Is Running the Clinical Trial?

Simcha IL-18, Inc.

Lead Sponsor

Trials

1

Recruited

320+

Merck Sharp & Dohme LLC

Industry Sponsor

Trials

4,096

Recruited

5,232,000+

Chirfi Guindo

Merck Sharp & Dohme LLC

Chief Marketing Officer since 2022

Degree in Engineering from Ecole Centrale de Paris, MBA from New York University Stern School of Business

Robert M. Davis

Merck Sharp & Dohme LLC

Chief Executive Officer since 2021

JD from Northwestern University Pritzker School of Law, MBA from Northwestern University Kellogg Graduate School of Management, Bachelor's in Finance from Miami University

Published Research Related to This Trial

Therapeutic cancer vaccines effectively stimulate the immune system to target and destroy cancer cells, leading to long-term remissions in some patients with advanced disease.

Various types of cancer vaccines, including inactivated tumor cells and heat shock protein vaccines, have been developed and tested in clinical trials, showing promise in enhancing the body's immune response against tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapeutic cancer vaccines. Morris, LF., Ribas, A.[2007]

The study identifies IL-18BP as a significant barrier to the effectiveness of IL-18 in cancer therapy, as it is frequently upregulated in various tumors and limits IL-18's anti-tumor activity.

An engineered 'decoy-resistant' IL-18 (DR-18) was developed, which showed potent anti-tumor effects in mouse models by enhancing CD8+ T cell function and natural killer cell activity, suggesting a promising new approach for immunotherapy against resistant tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

IL-18BP is a secreted immune checkpoint and barrier to IL-18 immunotherapy. Zhou, T., Damsky, W., Weizman, OE., et al.[2022]

Using dendritic cells modified with a recombinant adenovirus encoding interleukin-18 (rAd/IL-18) significantly enhances the generation and activation of tumor-specific cytotoxic T lymphocytes (CTLs), which are crucial for effective cancer treatment.

The study demonstrated that these engineered dendritic cells not only improve the maturation of CTLs but also increase their ability to kill breast cancer cells expressing the MAGE-A3 antigen, suggesting a promising approach to boost the efficacy of adoptive cell transfer therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Human dendritic cells engineered to secrete interleukin-18 activate MAGE-A3-specific cytotoxic T lymphocytes in vitro. Fan, X., Ye, M., Xue, B., et al.[2012]

The BNT162b2 vaccine demonstrated a high efficacy in solid cancer patients undergoing systemic chemotherapy, with 98.4% of participants showing a positive antibody response three months after the second dose.

The vaccine was found to be safe, as none of the 63 patients required postponement or discontinuation of their chemotherapy due to adverse reactions from the vaccination.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Prospective Study Regarding the Efficacy and Safety of the BNT162b2 Vaccine in Patients With Solid Malignancies Undergoing Systemic Chemotherapy. Yamasaki, E., Shimamoto, F., Nishikawa, H., et al.[2022]

Preclinical studies show that CD19-specific CAR-modified T cells that secrete IL-12 can effectively eliminate established tumors without the need for prior conditioning regimens, making this approach safer for patients who cannot tolerate such treatments.

The effectiveness of these modified T cells relies on both CD4(+) and CD8(+) T-cell subsets, autocrine IL-12 stimulation, and the ability to resist inhibition from T regulatory cells, suggesting a robust mechanism for enhancing anti-tumor responses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tumor-targeted T cells modified to secrete IL-12 eradicate systemic tumors without need for prior conditioning. Pegram, HJ., Lee, JC., Hayman, EG., et al.[2021]

The combination of mRNA constructs encoding IL12 and decoy-resistant IL18 (DR-18) shows strong antitumor effects by inducing significant IFNγ release and enhancing the activation of CD8+ T cells, which are crucial for effective immune responses against tumors.

When administered intratumorally in mice, this combination not only targets the treated tumor but also delays the growth of distant tumors, especially when combined with anti-PD-1 antibody treatment, suggesting a promising strategy for immunotherapy in cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intratumoral Gene Transfer of mRNAs Encoding IL12 in Combination with Decoy-Resistant IL18 Improves Local and Systemic Antitumor Immunity. Cirella, A., Bolaños, E., Di Trani, CA., et al.[2023]

The novel PD-L1 B-cell peptide vaccine (PDL1-Vaxx) has shown strong immunogenicity and the ability to inhibit tumor growth in various animal models, demonstrating its potential as a safe checkpoint inhibitor vaccine.

When combined with the HER-2 vaccine (B-Vaxx), PDL1-Vaxx exhibited synergistic effects in tumor inhibition, suggesting that combining immuno-oncology agents could enhance treatment efficacy for cancer patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A newly discovered PD-L1 B-cell epitope peptide vaccine (PDL1-Vaxx) exhibits potent immune responses and effective anti-tumor immunity in multiple syngeneic mice models and (synergizes) in combination with a dual HER-2 B-cell vaccine (B-Vaxx). Guo, L., Overholser, J., Darby, H., et al.[2022]

Therapeutic cancer vaccines aim to treat established tumors by inducing strong immune responses, particularly through the use of antigen-presenting cells like dendritic cells, which can be enhanced by transfecting them with tumor antigens.

Recent studies show that using tumor cells expressing anti-CD137 single-chain Fv fragments can effectively engage immune cells to destroy tumors, even those with low immunogenicity, suggesting a promising direction for future cancer vaccine development.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapeutic vaccination with tumor cells that engage CD137. Hellstrom, KE., Hellstrom, I.[2018]

The IL-18 gene-modified, C215Fab-SEA-coated tumor cell vaccine effectively stimulated the immune system, leading to significant expansion of CD4+ and CD8+ T cells in mice, indicating a strong antitumor immune response.

This vaccine provided protective immunity against tumor challenges, demonstrating its potential as an effective immunotherapy for melanoma by enhancing tumor-specific immune responses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vaccination with IL-18 gene-modified, superantigen-coated tumor cells elicits potent antitumor immune response. Wang, Q., Yu, H., Zhang, L., et al.[2019]

In a study involving 96 mice with spontaneous metastatic lung cancer, treatment with tumor antigen-pulsed, IL-18 gene-modified dendritic cells significantly reduced lung weight and the number of metastatic nodes, indicating effective tumor suppression.

This treatment also led to longer survival times and enhanced immune responses, including increased activity of cytotoxic T cells and natural killer (NK) cells, demonstrating its potential as a powerful immunotherapy for lung cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Treatment of spontaneous metastatic lung cancer with tumor antigen-pulsed, interleukin-18 gene-modified dendritic cells]. Chen, J., Cao, X., Xiu, Q.[2012]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04787042

NCT04787042 | Phase 1a and Phase 2 Study for Safety, ... 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 ...

2. biospace.com biospace.com/press-releases/simcha-therapeutics-presents-preclinical-data-demonstrating-potential-for-decoy-resistant-il-18-to-enhance-efficacy-of-bi-specific-t-cell-engagers

Simcha Therapeutics Presents Preclinical Data ... Data presented at the conference showed that adding ST-067 to treatment with BiTEs enhanced tumor growth inhibition without observed weight loss ...

3. withpower.com withpower.com/trial/phase-2-squamous-cell-carcinoma-of-head-and-neck-6-2021-ee538

ST-067-001 for Solid Tumors This trial is testing a new drug called ST-067 on patients with certain types of cancer that have not responded to previous treatments.

4. simchatx.com simchatx.com/science/

Science Simcha has engineered the first “decoy-resistant” IL-18 variant, ST-067, that is completely impervious to IL-18BP and can maintain strong immune stimulation in ...

5. massgeneral.trialstoday.org massgeneral.trialstoday.org/?page=eJyLViooSi3LzC8tVtJR8nMOMTC1NDQzNrZU0tG1hAEdYz1DI2MDA0sjHUNzQ3MjAyjQUcpLLjEwMzAzMjcxVYoFANJpEbw-

Mass General - Division of Clinical Research The goal of the study is to generate a biorepository of longitudinal biofluids-blood (plasma and serum), cerebral spinal fluid (CSF) and urine linked to ...

6. jitc.bmj.com jitc.bmj.com/content/11/Suppl_1/A829

736 A phase 1/2 open-label, dose-escalation study of ST ... A decoy-resistant variant of IL-18 (ST-067) has been developed which binds to IL-18Ra but not IL-18 BP. In murine colorectal and melanoma ...

7. insight.jci.org insight.jci.org/articles/view/184545

Decoy-resistant IL-18 reshapes the tumor ... A “decoy-resistant” form of IL-18 (DR-18), that avoids sequestration by IL-18BP while maintaining its immunostimulatory potential, has recently been developed.

8. simchatx.com simchatx.com/category/news/press-releases/

Press Releases Archives ST-067 is currently being studied both as a monotherapy and in combination with KEYTRUDA® (pembrolizumab) in Phase 1/2 clinical trials, in patients with solid ...