SGN1 Injection for Solid Tumors

Recruiting at 9 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: Immunosuppressants, Antibiotics

Disqualifiers: CNS metastases, Autoimmune diseases, Cardiac diseases, 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: 6

70 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test a new treatment called SGN1 for individuals with advanced solid tumors that have not responded to standard treatments. SGN1 targets tumors dependent on a nutrient called methionine, effectively starving them by injecting an enzyme that breaks down this nutrient. Suitable candidates for this trial include those with advanced tumors that can be directly injected and have no remaining treatment options. As a Phase 1 trial, participants will be among the first to receive this treatment, aiding researchers in understanding how SGN1 works in humans.

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.

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

Research shows that SGN1 targets certain cancers by using a microbe to remove methionine, an important nutrient, from tumors. This process may help break down cancer cells and prevent their spread.

Regarding safety, earlier studies have examined how well patients tolerate SGN1. Researchers aim to determine the safest dose that patients can manage. In these studies, one patient experienced a complete response, with their cancer disappearing entirely. Another six patients had stable disease, meaning their cancer did not worsen for 6 to 16 months.

While these results are promising, SGN1 remains in early testing. Researchers continue to learn about potential side effects and its safety for broader use. Those considering joining a trial should consult their doctor to understand what these findings might mean for them. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for solid tumors, which often involve systemic chemotherapy or targeted therapies, SGN1 takes a different approach by being injected directly into the tumor. This intratumoral delivery method is designed to maximize the drug's impact right where it's needed while potentially reducing systemic side effects. Researchers are excited about SGN1 because it uses a novel active ingredient that leverages a unique mechanism aimed at triggering a more robust immune response against the tumor. This could offer a new way to treat solid tumors that are resistant to existing therapies.

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

Research shows that SGN1 could be a promising treatment for solid tumors. This treatment targets methionine, a nutrient essential for tumor growth. SGN1, a special type of bacteria, enters tumors and breaks down methionine, effectively starving the cancer cells. Studies have shown that this method can destroy tumor cells and may also help prevent cancer from spreading. Additionally, SGN1 enhances the effects of other cancer treatments. While more research is needed, early results suggest it could be a powerful option for fighting certain types of cancer. Participants in this trial will receive SGN1 injections directly into the target lesion to evaluate its safety and efficacy. ^{1 2 3 4 6}

Are You a Good Fit for This Trial?

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

Patients must understand and voluntarily sign the informed consent form

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• SGN1

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.

How Is the Trial Designed?

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

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+

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

Published Research Related to This Trial

SGN-B6A is an antibody-drug conjugate specifically targeting integrin beta-6, which is overexpressed in various solid tumors and associated with poor prognosis, showing promising preclinical efficacy in models of non-small cell lung, pancreatic, pharyngeal, and bladder cancers.

In nonclinical studies, SGN-B6A was well-tolerated in cynomolgus monkeys at doses up to 6 mg/kg, with dose-limiting hematologic toxicities but no significant target-mediated toxicity, paving the way for a phase I clinical trial to assess its safety and effectiveness in humans.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

SGN-B6A: A New Vedotin Antibody-Drug Conjugate Directed to Integrin Beta-6 for Multiple Carcinoma Indications. Lyon, RP., Jonas, M., Frantz, C., et al.[2023]

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]

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]

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]

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]

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]

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]

Citations

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

NCT05103345 | Study of SGN1 Administered Via ... Objectives: To characterize safety, tolerability, MTD and OBD of intratumoral injection of SGN1 in patients with advanced solid tumors, and to preliminarily ...

2. 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, ...

3. trialfinder.panfoundation.org trialfinder.panfoundation.org/en-US/trial/listing/309680

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, ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10313934/

Targeted deprivation of methionine with engineered ... The microbe, SGN1, selectively depletes methionine in tumors, leading to oncolysis and suppression of metastasis in several types of tested cancer.

5. jitc.bmj.com jitc.bmj.com/content/12/2/e008238?rss=1

Salmonella-mediated methionine deprivation drives ... These findings reveal that SGN1 acts synergistically with ICIs and produces an enhanced antitumor effect on melanoma cells compared with either ...

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

SGN1 Injection for Solid Tumors The treatment showed modest clinical activity, with one patient achieving a complete response and six others maintaining stable disease for 6 to 16 months, ...