SGN1 Injection for Solid Tumors

Recruiting at7 trial 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: Immunosuppressants, Antibiotics

Disqualifiers: CNS metastases, Autoimmune diseases, Cardiac diseases, others

No Placebo Group

Approved in 2 Jurisdictions

Trial Summary

What is the purpose of this trial?

This trial tests SGN1, a modified bacterium injected into tumors, in patients with advanced solid tumors that don't respond to other treatments. SGN1 works by starving the tumor of a vital nutrient, methionine. The study aims to find the safest and most effective dose while checking for any side effects.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications. However, it mentions that certain treatments, like immunosuppressive drugs and recent anti-tumor therapies, should not be taken before starting the trial. It's best to discuss your specific medications with the trial team.

What safety data exists for SGN1 Injection for Solid Tumors?

SGN-30, a similar treatment, was tested in a study with 24 patients and showed mild side effects like nausea, fatigue, and fever, with some serious cases of herpes zoster, influenza, and pneumonia. Another related treatment, SGN-B6A, was tested in monkeys and tolerated well, but had dose-limiting blood-related side effects. SGN-CD70A, another related treatment, caused significant blood-related side effects in humans, such as low platelet counts, but showed some antitumor activity. ^{1 2 3 4 5}

How is the drug SGN1 different from other treatments for solid tumors?

SGN1 is unique because it is an antibody-drug conjugate (ADC) that targets specific proteins on cancer cells, delivering a powerful drug directly to the tumor, which may reduce damage to healthy cells. This targeted approach is different from traditional chemotherapy, which affects both cancerous and healthy cells. ^{2 4 6 7 8}

Research Team

Eligibility Criteria

Adults aged 18-75 with advanced solid tumors that haven't responded to standard treatments or for whom no standard treatment exists. They must have a life expectancy of at least 12 weeks, an ECOG score of 0-1, and be able to follow up post-treatment. Women of childbearing age must use contraception.

Inclusion Criteria

I agree to use effective birth control methods.

I am between 18 and 75 years old.

I meet the specific requirements regarding menopause, sterility, pregnancy, and contraception.

Exclusion Criteria

Symptomatic patients at risk of life-threatening complications

My heart condition is not well controlled with treatment.

I have active brain metastases that are not under control.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Phase I open-label, dose escalation study to characterize safety, tolerability, MTD, and OBD of intratumoral injection of SGN1

Varies per cohort

Weekly visits for 3 weeks followed by 1-week rest in 28-day cycles

Dose Expansion

Phase Ib/IIa study to preliminarily investigate the efficacy and safety of SGN1 in specific tumor subtypes

Varies per cohort

Weekly visits for 3 weeks followed by 1-week rest in 28-day cycles

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• SGN1 (Virus Therapy)

Trial Overview SGN1 is being tested as a potential cancer therapy for its ability to starve tumors by depleting essential amino acids. It's administered directly into the tumor and this study aims to find the safest dose with the best response in various advanced cancers.

Participant Groups

Group I: Cohort Experimental Treatment 1 Intervention

SGN1 will be injected into the target lesion intratumorally. According to the dose levels, the administered dose will be 0.5×108 CFU, 1×108 CFU, 2×108 CFU, 4×108 CFU, 6×108 CFU (optional). The patient will be administered once every week for 3 consecutive weeks followed by 1-week rest in 28-day treatment cycles. The duration of administration is until isease complete response/inability to continue intratumoral administration or disease progression, or intolerable toxicity or death or voluntary withdrawal or end of study, whichever came first. The standard 3+3 dose escalation algorithm will be applied to explore dose limiting toxicity (DLTs) in at least 4 sequential cohorts with 3- 6 patients and identify the maximally tolerated dose (MTD). When the cohort is completed in Part 1, the Part 2 study could be started according to the SMC evaluation. Enrollment of 2-4 dose level expansions will be opened to determine the safety and efficacy of SGN1 in specific tumor types

Who Is Running the Clinical Trial?

Guangzhou Sinogen Pharmaceutical Co., Ltd

Lead Sponsor

Trials

2

Recruited

140+

Pharmaron

Industry Sponsor

Trials

4

Recruited

180+

Pharmaron

Collaborator

Trials

4

Recruited

180+

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

Findings from Research

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, and the maximum tolerated dose was not reached.

The treatment showed modest clinical activity, with one patient achieving a complete response and six others maintaining stable disease for 6 to 16 months, indicating potential effectiveness in targeting CD30(+) malignancies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase 1 multidose study of SGN-30 immunotherapy in patients with refractory or recurrent CD30+ hematologic malignancies. Bartlett, NL., Younes, A., Carabasi, MH., 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]

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]

The HN-1 peptide has been identified as a promising delivery vector for anticancer drugs, effectively targeting and infiltrating solid tumors like head and neck squamous cell carcinoma (HNSCC) by binding to the discoidin-domain receptor 1 (DDR1), which is overexpressed in these cancers.

The study provides insights into the mechanism of HN-1's action, showing that it is internalized through energy-dependent clathrin-mediated endocytosis, suggesting that targeting DDR1 could enhance the efficacy of treatments for metastatic cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tumor specifically internalizing peptide 'HN-1': Targeting the putative receptor retinoblastoma-regulated discoidin domain receptor 1 involved in metastasis. Hong, FU., Castro, M., Linse, K.[2022]

Denintuzumab mafodotin demonstrated significant anti-leukemic activity in preclinical models of pediatric acute lymphoblastic leukemia (ALL), delaying progression in seven out of eight patient-derived xenografts (PDXs) tested.

When combined with standard chemotherapy (vincristine, dexamethasone, and l-asparaginase), denintuzumab mafodotin enhanced therapeutic effects, suggesting a potential for improved treatment strategies in pediatric ALL.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preclinical activity of the antibody-drug conjugate denintuzumab mafodotin (SGN-CD19A) against pediatric acute lymphoblastic leukemia xenografts. Jones, L., McCalmont, H., Evans, K., et al.[2023]

Brentuximab vedotin (SGN-35) is an effective antibody-drug conjugate that targets the CD30 antigen, showing response rates of 75% in Hodgkin lymphoma patients (n = 102) and 87% in anaplastic large cell lymphoma patients (n = 30) during phase II trials.

The efficacy of SGN-35 may not only stem from the direct cytotoxic effects of its drug component, MMAE, but also from its ability to signal malignant cells and affect the tumor microenvironment, potentially enhancing overall treatment effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brentuximab Vedotin (SGN-35). Katz, J., Janik, JE., Younes, A.[2019]

References

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

A phase 1 multidose study of SGN-30 immunotherapy in patients with refractory or recurrent CD30+ hematologic malignancies. [2021]

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

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

3. 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]

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

SGN-B6A: A New Vedotin Antibody-Drug Conjugate Directed to Integrin Beta-6 for Multiple Carcinoma Indications. [2023]

5. 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]

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

Tumor specifically internalizing peptide 'HN-1': Targeting the putative receptor retinoblastoma-regulated discoidin domain receptor 1 involved in metastasis. [2022]

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

Preclinical activity of the antibody-drug conjugate denintuzumab mafodotin (SGN-CD19A) against pediatric acute lymphoblastic leukemia xenografts. [2023]

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

Brentuximab Vedotin (SGN-35). [2019]