SGN1 for Solid Tumors

Recruiting in Palo Alto (17 mi)

+6 other locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1 & 2

Recruiting

Sponsor: Guangzhou Sinogen Pharmaceutical Co., Ltd

Must not be taking: Steroids, Antibiotics

Disqualifiers: Cardiac disease, CNS metastasis, others

No Placebo Group

Approved in 2 Jurisdictions

Trial Summary

What is the purpose of this trial?

Objectives:To assess the safety and tolerability followed by a dose expansion study to characterize safety, and preliminary efficacy of SGN1 in participants with refractory solid tumors. Study Rationale:The mechanism of action for SGN1 is based on the fact that most tumors are methionine dependent. SGN1 is designed to be used as a tumor therapeutic bacterium that can preferentially replicate and accumulate in tumors and starve them of essential amino acids by delivering the oncolytic enzyme L-Methioninase. Patient Population:The treatment populations shall be patients presenting with histologically confirmed advanced and/or metastatic solid tumors that are refractory to standard therapy and for which no other conventional therapy exists.

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.

What data supports the effectiveness of the drug SGN1 for solid tumors?

SGN-35, a similar drug, has shown effectiveness in treating Hodgkin lymphoma and anaplastic large cell lymphoma by targeting specific cancer markers. Additionally, SGN-CD70A, another related drug, demonstrated strong antitumor activity in T-cell lymphomas, suggesting potential for similar treatments in solid tumors. ^{1 2 3 4 5}

What safety data exists for SGN1 in humans?

There is no specific safety data available for SGN1 in humans from the provided research articles. ^{5 6 7 8 9}

Research Team

Eligibility Criteria

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 am between 18 and 75 years old.

I can attend all follow-up appointments after treatment.

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.

Trial Timeline

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)

Treatment Details

Interventions

• SGN1 (Virus Therapy)

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.

Participant Groups

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 .

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+

Findings from Research

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-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]

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]

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]

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-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]

References

1. England pubmed.ncbi.nlm.nih.gov

HER-2 Neu gene: A valuable therapeutic target in metastatic mucoepidermoid carcinoma. [2021]

2. United States 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. [2022]

3. England pubmed.ncbi.nlm.nih.gov

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

4. United States pubmed.ncbi.nlm.nih.gov

Targeting CD70 in cutaneous T-cell lymphoma using an antibody-drug conjugate in patient-derived xenograft models. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Intracellular activation of SGN-35, a potent anti-CD30 antibody-drug conjugate. [2021]

6. England 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. [2023]

7. United States 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. [2020]

8. Switzerland 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. [2023]

9. England pubmed.ncbi.nlm.nih.gov

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