ASKG915 for Solid Tumors

Recruiting at 1 trial location

Overseen By Executive Director, Clinical Operations

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: AskGene Pharma, Inc.

Disqualifiers: Metastasis, Cardiovascular diseases, Autoimmune, others

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

Compensation: Varies

Number of Visits: Unknown

104 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment, ASKG915, to determine its safety and tolerability in people with advanced solid tumors. It targets those who have exhausted all standard treatments without success. The trial begins with small doses of ASKG915, gradually increasing them to monitor side effects and benefits. Suitable candidates have advanced cancer unresponsive to current treatments and a life expectancy of at least three months. As a Phase 1 trial, this research aims to understand how the treatment works in people, offering participants the opportunity to be among the first to receive it.

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

The trial does not specify if you need to stop taking your current medications, but you cannot have received any antitumor therapy in the 4 weeks before starting the study drug.

Is there any evidence suggesting that ASKG915 is likely to be safe for humans?

Research shows that ASKG915 is currently undergoing its first clinical trial with humans, so its safety profile is not yet fully known. In these early studies, researchers primarily assess the treatment's safety and tolerability. Currently, limited information is available about side effects or how well participants tolerate ASKG915.

As a Phase 1 study, the primary focus is on testing various doses to observe the body's reactions. The goal is to identify any unwanted effects and determine the safest dose for future studies. This stage is crucial for understanding safety, but it marks only the beginning of the testing process. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for solid tumors, which often include chemotherapy, radiation, or targeted therapies aimed at specific proteins, ASKG915 offers a new approach by potentially targeting different pathways involved in tumor growth. Researchers are excited about ASKG915 because it involves a unique mechanism of action that could overcome resistance seen in some patients with existing therapies. By exploring single or multiple ascending doses, ASKG915 may also offer insights into optimal dosing strategies that could enhance its effectiveness and safety profile.

What evidence suggests that ASKG915 might be an effective treatment for solid tumors?

Research shows that ASKG915, the investigational treatment in this trial, has shown promising results in early studies. It stays in the body longer, potentially increasing its effectiveness. In tests with mice, ASKG915 helped shrink tumors, suggesting it might have similar effects in humans. This treatment combines two components: anti-PD-1, which helps the immune system attack cancer cells, and IL-15, a protein that boosts the immune response. This combination has proven more effective than using anti-PD-1 alone. Although human studies provide limited information, these early results suggest that ASKG915 could be a promising option for treating advanced solid tumors. ^{2 3 4 6 7}

Who Is on the Research Team?

Barbara Hickingbottom, MD

Principal Investigator

Ask-Gene Pharma, Inc.

Are You a Good Fit for This Trial?

This trial is for adults with advanced solid tumors that haven't responded to standard treatments or have no standard options left. They should be relatively stable (ECOG ≤ 2), expected to live at least 3 more months, and meet specific lab test criteria. People can't join if they've had recent antitumor therapy, live vaccines, autoimmune diseases, problematic fluid buildup needing drainage, are pregnant/breastfeeding/planning pregnancy during the study period, have brain metastases or serious heart/stroke issues.

Inclusion Criteria

Life expectancy of ≥ 3 months

The results of the laboratory tests must meet all criteria

My cancer does not respond to standard treatments or I cannot tolerate them.

Exclusion Criteria

I have had fluid drained from my abdomen or chest.

My cancer has spread to my brain or its coverings.

I have had serious heart or stroke-related diseases.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Participants receive single or multiple ascending doses of ASKG915 to evaluate safety, tolerability, and pharmacokinetics

3 weeks

Multiple visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Long-term Follow-up

Evaluation of immunogenicity and incidence of anti-drug antibodies

Up to 2 years

What Are the Treatments Tested in This Trial?

Interventions

• ASKG915

Trial Overview The trial is testing ASKG915's safety and how it affects the body in patients with certain advanced solid tumors. It's an early-phase study where researchers gradually increase doses to find a safe amount while monitoring how participants' bodies process the drug.

How Is the Trial Designed?

Group I: ASKG915 Experimental Treatment 1 Intervention

Single or multiple ascending dose of ASKG915.

Who Is Running the Clinical Trial?

AskGene Pharma, Inc.

Lead Sponsor

Trials

7

Recruited

1,200+

Jiangsu Aosaikang Pharmaceutical Co., Ltd.

Industry Sponsor

Trials

15

Recruited

2,600+

Published Research Related to This Trial

ASK1 deficiency in mice enhances the ability of natural killer (NK) cells to clear tumor cells during the early stages of metastasis, suggesting a protective role against tumor spread.

The study found that ASK1 deficiency leads to increased production of immune-related cytokines and recruitment of NK cells, indicating that targeting ASK1 could be a promising strategy for improving cancer immunotherapy and combating metastasis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

ASK1 suppresses NK cell-mediated intravascular tumor cell clearance in lung metastasis. Fujimoto, M., Kamiyama, M., Fuse, K., et al.[2021]

Transfection with a dominant-negative mutant of ASK-1 (Ad-DN-ASK-1) in colorectal cancer cells significantly inhibited cell proliferation and induced apoptosis, suggesting that inhibiting ASK-1 can be a potential strategy for cancer treatment.

In vivo studies showed that Ad-DN-ASK-1 reduced tumor volume in HT-29 xenografts in mice, with evidence of apoptosis indicated by the presence of cleaved caspase-3, highlighting its potential as an effective antitumor agent.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Growth inhibition of colon cancer cells by transfection of dominant-negative apoptosis signal-regulating kinase-1. Kuwamura, H., Tominaga, K., Shiota, M., et al.[2012]

The ASK family of proteins, particularly ASK1, plays a crucial role in regulating tumor formation and progression by influencing innate immunity and apoptosis, which are key processes in cancer biology.

In a murine model of lung metastasis, the absence of ASK1 in the host was found to reduce the spread of tumors to the lungs, suggesting that ASK1 may be a potential target for therapeutic strategies against cancer metastasis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Functional Analysis of Apoptosis Signal-regulating Kinase Family in a Murine Model of Tumor Metastasis]. Kamiyama, M., Naguro, I., Ichijo, H.[2019]

The FDA-approved therapeutic vaccine Sipuleucel-T marks a significant advancement in tumor immunotherapy for prostate cancer, highlighting the need for similar strategies in breast cancer, which is the most common cancer in women.

Research shows that targeting ISG15, a protein highly expressed in many breast cancers and linked to poor treatment outcomes, can effectively reduce tumor burden through immunotherapy, suggesting it as a promising new target for breast cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The ubiquitin-like protein, ISG15, is a novel tumor-associated antigen for cancer immunotherapy. Wood, LM., Pan, ZK., Seavey, MM., et al.[2021]

Compound 15, a novel ASK1 inhibitor, demonstrated strong in vitro activity against ASK1 kinase and effectively protected intestinal epithelial cells from TNF-α-induced damage, showing potential for treating inflammatory bowel disease (IBD).

The compound was found to be non-cytotoxic at concentrations up to 25 μM and works by inhibiting the ASK1-p38/JNK signaling pathway, which is involved in cell survival and apoptosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Design, synthesis and biological evaluation of 1H-indazole derivatives as novel ASK1 inhibitors. Hou, S., Yang, X., Yang, Y., et al.[2021]

The study identifies a novel gene, designated as the 'ASK3 gene', which encodes proteins that are involved in regulating apoptosis and stress responses, showing potential as a therapeutic target for various diseases.

Knockdown of ASK3 in HeLa cells provided protection against cell death caused by stressors like anti-Fas antibodies and TNF-alpha, indicating its significant role in apoptotic pathways and suggesting its importance in developing treatments for conditions involving excessive cell death.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

ASK3, a novel member of the apoptosis signal-regulating kinase family, is essential for stress-induced cell death in HeLa cells. Kaji, T., Yoshida, S., Kawai, K., et al.[2011]

The IP2-ATLANTA trial is a phase II study investigating whether adding local and metastasis-directed treatments to standard care can improve progression-free survival (PFS) in men with newly diagnosed, hormone-sensitive metastatic prostate cancer, with a total of 918 participants planned for the main study.

Participants will be followed for at least 2 years to assess PFS and side effects, with the trial aiming to provide insights into the effectiveness of combining systemic therapy with local interventions like surgery or radiotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Additional Treatments to the Local tumour for metastatic prostate cancer-Assessment of Novel Treatment Algorithms (IP2-ATLANTA): protocol for a multicentre, phase II randomised controlled trial. Connor, MJ., Shah, TT., Smigielska, K., et al.[2021]

A meta-analysis of 1040 patients with solid tumors found that high levels of soluble programmed death ligand-1 (sPD-L1) in the blood are significantly associated with worse overall survival, indicating a poor prognosis.

The study suggests that measuring sPD-L1 levels could serve as a predictive biomarker for patients with solid tumors, helping to identify those at higher risk for poor outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prognostic significance of circulating soluble programmed death ligand-1 in patients with solid tumors: A meta-analysis. Wei, W., Xu, B., Wang, Y., et al.[2022]

ISG15 is often found to be overexpressed in many human cancers, indicating it may promote tumor growth.

Despite its protumor role, ISG15 also has the potential to enhance immune responses against tumors, suggesting that therapies targeting its immunomodulatory effects could be beneficial for cancer patients with high ISG15 levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

ISG15: A double edged sword in cancer. Desai, SD.[2022]

Soluble programmed death-1 ligand-1 (sPD-L1) levels were significantly higher in lung cancer patients compared to healthy controls, indicating its potential role as a biomarker for lung cancer.

Higher sPD-L1 levels were associated with more advanced stages of non-small cell lung cancer (NSCLC) and poorer overall health, suggesting that elevated sPD-L1 may indicate a negative prognosis for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Analysis of soluble programmed death-1 ligand-1 of lung cancer patients with different characteristics. Zhu, HB., Song, X.[2023]

Citations

1. ask-gene.com ask-gene.com/askgene-achieves-first-in-human-milestone-for-askg915-a-first-in-class-anti-pd-1-il-15-prodrug-for-the-treatment-of-solid-tumors/

AskGene Achieves “First in Human” Milestone for ... Preclinical data showed that ASKG915 has extended PK, significantly better efficacy than anti-PD-1 antibody monotherapy, and an expanded ...

2. withpower.com withpower.com/trial/phase-1-neoplasms-5-2023-80b05

ASKG915 for Solid Tumors In vivo studies showed that Ad-DN-ASK-1 reduced tumor volume in HT-29 xenografts in mice, with evidence of apoptosis indicated by the presence of cleaved ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11876874/

First-in-human phase I study to evaluate safety, tolerability ... This phase I study (NCT04628780) evaluated the safety, tolerability, pharmacokinetics (PK), pharmacodynamics, and potential clinical benefits of PF-07209960

4. bioworld.com bioworld.com/articles/692939-askgene-cleared-to-enter-clinic-with-anti-pd-1-il-15-prodrug-fusion-molecule-askg-915

Askgene cleared to enter clinic with anti-PD-1/IL-15 ... Preclinical data show that ASKG-915 has extended pharmacokinetics and significantly better efficacy than anti-PD-1 antibody monotherapy, as well ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S2666379124002003

Next-generation anti-PD-L1/IL-15 immunocytokine elicits ... Here we propose a next-generation immunocytokine concept involving the design of LH05, a tumor-conditional anti-PD-L1/interleukin-15 (IL-15) prodrug.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT05867420

A Study of ASKG915 in Patients With Selected Advanced ... The study is a Phase 1dose escalation study to evaluate the safety, tolerability, and pharmacokinetics of ASKG915 as a single agent in patients with selected ...

7. synapse.patsnap.com synapse.patsnap.com/drug/9d3172d77b2b434abe5ede2667e8ac9e

ASKG-915 - Drug Targets, Indications, Patents A Phase 1 Dose Escalation Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of ASKG915 as a Single Agent in Patients With Selected Advanced ...