SGN1 for Solid Tumors

Recruiting at 7 trial locations

Overseen By Weiyun Jia

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Guangzhou Sinogen Pharmaceutical Co., Ltd

Must not be taking: Steroids, Antibiotics

Disqualifiers: Cardiac disease, CNS metastasis, others

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

70 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called SGN1 for individuals with solid tumors unresponsive to standard treatments. SGN1 targets tumors by depriving them of certain nutrients, potentially slowing or stopping their growth. The study will assess SGN1's safety and effectiveness at different doses. Suitable candidates have advanced cancers such as lung, breast, or ovarian cancer and have seen little success with conventional therapies. Participants should have completed cancer treatments like chemotherapy or immunotherapy at least four weeks before joining the trial. As a Phase 1 trial, this research focuses on understanding how SGN1 works in people, offering participants the opportunity to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

The trial requires that you stop any anti-tumor therapy, including chemotherapy, immunotherapy, biological agents, hormone therapy, and radiotherapy, at least 4 weeks before starting the study drug. If you are taking steroid hormones, you must not exceed certain doses 14 days before enrollment.

Is there any evidence suggesting that SGN1 is likely to be safe for humans?

Research has shown that SGN1 appears safe for use. In a study involving patients with advanced solid tumors, researchers tested SGN1 to assess its tolerability. The early results indicated that patients generally managed the treatment well, experiencing only mild side effects. This suggests the treatment is well-tolerated in humans so far. However, as the treatment remains under study, more information will emerge as researchers continue their work. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

SGN1 is unique because it targets solid tumors differently than most standard treatments, which typically involve chemotherapy or radiation. Unlike those options, SGN1 is designed to be administered through a two-hour IV infusion, potentially offering a more targeted approach with fewer side effects. Researchers are excited about SGN1 because it might work more effectively across multiple tumor types and at different dosage levels, paving the way for more personalized cancer care.

What evidence suggests that SGN1 might be an effective treatment for solid tumors?

Research has shown that SGN1, the treatment tested in this trial, has potential against various solid tumors. In studies, SGN1 significantly shrank or even completely eliminated tumors, while also alleviating symptoms like severe weight loss due to illness. This treatment uses bacteria that specifically target tumors and deprive them of methionine, a vital nutrient for growth. Similar treatments have succeeded in other cancers, such as Hodgkin lymphoma, which boosts confidence in SGN1's potential. Early results suggest that SGN1 could be a promising option for patients whose tumors no longer respond to standard treatments. ^{1 5 6 7 8}

Are You a Good Fit for This Trial?

This trial is for adults aged 18-75 with advanced solid tumors that haven't responded to standard treatments or have no other treatment options. Participants must have at least one measurable tumor, be in relatively good health (ECOG status 0-1), and have a life expectancy of over three months. Women must not be pregnant or breastfeeding and use contraception if of childbearing potential; men also need to agree to use contraception.

Inclusion Criteria

I have chronic HBV or a history of HCV and meet specific health criteria.

I can attend all follow-up appointments after treatment.

I agree to use effective birth control methods.

Exclusion Criteria

Patients with specific medical conditions or risks as determined by the investigator

Patients with specific vaccination history

I had a salmonella infection in the last 6 months.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Open-label, dose escalation phase to determine the maximum tolerated dose (MTD) and observe dose-limiting toxicities (DLT).

28 days

Weekly visits for monitoring and dose adjustments

Dose Expansion

Open-label, dose expansion phase to further evaluate safety and preliminary efficacy in selected tumor types.

Varies based on patient response

Bi-weekly visits for treatment and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

2 visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• SGN1

Trial Overview

SGN1, a genetically modified Salmonella bacterium designed to target and kill cancer cells by starving them of methionine, an amino acid essential for tumor growth. This study will first determine the safe dosage levels (safety/tolerability) followed by an expansion phase to assess preliminary effectiveness against various refractory solid tumors.

How Is the Trial Designed?

Group I: Cohort Experimental Treatment 1 Intervention

In part 1\&2, cohorts of 3 patients will be enrolled. The first patient of each cohort in Part 1 will be admitted to an infusion unit and treated with an IV infusion of SGN1 over 2 hours. Patients in Part 1 will enter Part 2 for extension treatment after completing the 28-day DLT observation period. Up to 5 cohorts will be evaluated. Part 3 is an open-label, dose expansion phase.There will be at least 2 tumor types selected, expand between second to four dose level in each tumor type .

SGN1 is already approved in United States for the following indications:

Approved in United States as SGN1 for:

• Advanced solid tumors

Who Is Running the Clinical Trial?

Guangzhou Sinogen Pharmaceutical Co., Ltd

Lead Sponsor

Trials

2

Recruited

140+

Novotech Clinical Research USA, LLC

Collaborator

Trials

1

Recruited

70+

ClinChoice Enterprise Management (Shanghai) Limited Co., Ltd

Collaborator

Trials

1

Recruited

70+

Parexel

Industry Sponsor

Trials

322

Recruited

137,000+

Peyton Howell

Parexel

Chief Executive Officer

Master of Healthcare Administration from The Ohio State University, Bachelor of Arts in Health Communications from the University of Illinois

Dr. Austin Smith

Parexel

Chief Medical Officer since 2023

MD from the Royal College of Surgeons in Ireland

ClinChoice Enterprise Management (Shanghai) Limited

Collaborator

Trials

1

Recruited

70+

Published Research Related to This Trial

SGN-15 is a monoclonal antibody-doxorubicin conjugate being developed by Seattle Genetics for cancer treatment, currently in phase II clinical trials, indicating its potential efficacy in targeting tumors.

The technology licensed from Enzon enhances the ability of SGN-15 to penetrate tumors more effectively, which may improve its therapeutic action compared to traditional treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Technology evaluation: SGN-15, Seattle Genetics Inc. Smith, S.[2013]

An elderly male with HER-2 Neu overexpressing metastatic mucoepidermoid carcinoma showed a significant and sustained response to targeted therapies (Trastuzumab and Pertuzumab) for over 3 years, highlighting the potential efficacy of these treatments in salivary gland neoplasms.

Although Trastuzumab emtansine (TDM-1) initially continued this positive response, it had to be discontinued due to severe hepatotoxicity, indicating the need for careful monitoring of adverse effects in elderly patients undergoing targeted therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

HER-2 Neu gene: A valuable therapeutic target in metastatic mucoepidermoid carcinoma. Mohammed, T., Mangeshkar, S., Desai, A., et al.[2021]

The CD70-targeted antibody-drug conjugate SGN-75 showed modest antitumor activity in patients with relapsed or refractory CD70-positive non-Hodgkin lymphoma and metastatic renal cell carcinoma, with one complete response and two partial responses observed among 58 patients.

The treatment was generally manageable in terms of adverse events, with the Q3Wk dosing schedule being better tolerated than weekly dosing, although significant side effects like thrombocytopenia and ocular issues were noted.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I dose-escalation study of SGN-75 in patients with CD70-positive relapsed/refractory non-Hodgkin lymphoma or metastatic renal cell carcinoma. Tannir, NM., Forero-Torres, A., Ramchandren, R., et al.[2022]

SGN-35, an antibody-drug conjugate targeting CD30, effectively releases the potent drug MMAE inside CD30(+) cancer cells, achieving high intracellular concentrations that contribute to its therapeutic effects.

MMAE not only kills CD30(+) cells but can also diffuse to and exert cytotoxic effects on neighboring CD30(-) cells, enhancing the overall antitumor activity of SGN-35 in mixed tumor environments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intracellular activation of SGN-35, a potent anti-CD30 antibody-drug conjugate. Okeley, NM., Miyamoto, JB., Zhang, X., et al.[2021]

Larotrectinib and entrectinib, first-generation TRK inhibitors, are effective first-line treatments for advanced non-small cell lung cancer (NSCLC) with TRK gene fusions, showing rapid and long-lasting clinical benefits.

A safety analysis of 807 reports revealed that the most common adverse reactions were dizziness and pain, with no significant long-term safety concerns noted, indicating a favorable risk-benefit profile for these medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Safety Profiles of Two First-Generation NTRK Inhibitors: Analysis of Individual Case Safety Reports from the FDA Adverse Event Reporting System (FAERS) Database. Liguori, V., Gaio, M., Zinzi, A., et al.[2023]

SGN-30, a chimeric antibody targeting CD30, shows promising efficacy, particularly in patients with primary cutaneous CD30-positive lymphoproliferative disease and in those with relapsed or refractory systemic anaplastic large-cell lymphoma.

The drug is well tolerated even in patients with a history of stem cell transplantation, and it may work synergistically with chemotherapy, although the optimal dosing schedule is still to be determined.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

SGN-30: a basis for the effective treatment of CD30 positive hematopoietic malignancies. Pinter-Brown, LC.[2019]

A total of 3120 adverse event cases related to avapritinib were reported to the FDA, with 44% occurring within the first 30 days of treatment, highlighting the importance of monitoring patients closely during this period.

The study found that elderly male patients are at a higher risk for serious adverse events, indicating that clinicians should exercise caution when prescribing avapritinib to this demographic.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A post-marketing pharmacovigilance study of avapritinib: Adverse event data mining and analysis based on the United States Food and Drug Administration Adverse Event Reporting System database. Rong, L., Xie, M., Jiang, M., et al.[2023]

In a first-in-human study involving 20 patients with relapsed or refractory CD70-positive non-Hodgkin lymphoma, SGN-CD70A demonstrated modest antitumor activity, achieving 1 complete remission and 3 partial remissions, with some responses lasting over 42 weeks.

However, the treatment was associated with significant adverse effects, particularly thrombocytopenia occurring in 75% of patients, which limited the frequency of dosing and raised safety concerns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase 1 trial of SGN-CD70A in patients with CD70-positive diffuse large B cell lymphoma and mantle cell lymphoma. Phillips, T., Barr, PM., Park, SI., et al.[2020]

CD70 is highly expressed in T-cell lymphomas, particularly in cutaneous T-cell lymphoma (CTCL), making it a promising target for treatment.

The CD70-directed antibody-drug conjugate SGN-CD70A demonstrated significant antitumor activity in preclinical models, with multiple doses leading to complete tumor eradication and prolonged survival in tumor-bearing animals.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeting CD70 in cutaneous T-cell lymphoma using an antibody-drug conjugate in patient-derived xenograft models. Wu, CH., Wang, L., Yang, CY., et al.[2022]

Citations

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clinicaltrials.gov

clinicaltrials.gov/study/NCT05038150

Study of SGN1 in Patients With Advanced Solid Tumor

Objectives:To assess the safety and tolerability followed by a dose expansion study to characterize safety, and preliminary efficacy of SGN1 in participants ...

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ascopubs.org

ascopubs.org/doi/10.1200/JCO.2023.41.16_suppl.e15184

Effects of oncolytic bacteria, SGN1, against a broad ...

In investigator-initiated trial (IIT) studies, SGN1 significantly shrank, or completely lysed, patients' tumor and ameliorated cachexia, while ...

3.

withpower.com

withpower.com/trial/phase-1-neoplasms-9-2021-1efae

SGN1 for Solid Tumors · Recruiting Participants for Phase ...

SGN-35, a similar drug, has shown effectiveness in treating Hodgkin lymphoma and anaplastic large cell lymphoma by targeting specific cancer markers.

4.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC10836381/

Salmonella-mediated methionine deprivation drives ...

Compared with the PBS or VNP-V-treated groups, SGN1 significantly suppressed tumor growth at a dose of 2×105 or 2×106 CFU at 9 days post- ...

5.

georgiacancerinfo.org

georgiacancerinfo.org/clinical-trials/detail/5458

Study of SGN1 Administered Via Intratumoral Injection in ...

Summary. Objectives: To characterize safety, tolerability, MTD and OBD of intratumoral injection of SGN1 in patients with advanced solid tumors, ...

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clinicaltrials.gov

clinicaltrials.gov/ct2/show/NCT05103345?cond=SGN1&draw=2&rank=2

NCT05103345 | Study of SGN1 Administered Via ...

The purpose of Part 1 is to characterize safety, tolerability, MTD and OBD of intratumoral injection of SGN1 in patients with advanced solid tumors. Part 2 ...

7.

withpower.com

withpower.com/trial/phase-1-neoplasms-2-2022-f04b2

SGN1 Injection for Solid Tumors

In a Phase 1 study involving 24 patients with refractory Hodgkin lymphoma or CD30(+) non-Hodgkin lymphoma, SGN-30 was found to be safe with mild adverse effects ...

8.

cancer.gov

cancer.gov/clinicaltrials/NCI-2023-06281

Study of SGN1 Administered Via Intratumoral Injection in ...

Objectives: To characterize safety, tolerability, MTD and OBD of intratumoral injection of SGN1 in patients with advanced solid tumors, and to preliminarily ...