PTX-912 for Cancer

Recruiting at 2 trial locations

Overseen By Project Manager

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Proviva Therapeutics, Inc.

Must not be taking: Systemic steroids

Disqualifiers: Immunodeficiency, Active infection, Autoimmune, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 12 months

26 Participants Needed

Trial Summary

What is the purpose of this trial?

The goal of this clinical trial is to evaluate the safety and tolerability of escalating doses of PTX-912 in patients with locally advanced or metastatic solid tumors. To evaluate the PK and immunogenicity profile of PTX-912. To evaluate the preliminary anti-tumor activity of PTX-912. Participants will be treated with PTX-912 via iv infusion, every 2 weeks until progression of disease, unacceptable toxicity, or 12 months of total study therapy.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, it mentions that you must recover from any toxicities from previous treatments and not have any active infections or autoimmune diseases requiring treatment. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the treatment PTX-912 for cancer?

Research on similar treatments, like IL-2 fusion proteins, shows they can help the immune system fight cancer by targeting tumors and enhancing the body's natural defenses. For example, studies have shown that these proteins can eliminate cancer in animal models by boosting the activity of immune cells. ^{1 2 3 4 5}

What safety data exists for PTX-912 or similar IL-2 fusion proteins in humans?

IL-2 fusion proteins, like PTX-912, have been studied for cancer treatment, but they can cause side effects ranging from flu-like symptoms to serious conditions like vascular leak syndrome (fluid leakage from blood vessels). Efforts are ongoing to reduce these toxicities by modifying how IL-2 is delivered and activated in the body. ^{2 6 7 8 9}

What makes the drug PTX-912 unique for cancer treatment?

PTX-912 is unique because it combines an anti-erbB2 antibody with interleukin-2 (IL-2), allowing it to specifically target cancer cells that overexpress the erbB2 protein and stimulate the immune system to attack these cells. This fusion protein is smaller and may penetrate tumors more effectively than traditional antibody-IL-2 combinations, potentially offering better treatment outcomes. ^{2 5 6 7 10}

Eligibility Criteria

This trial is for adults with advanced solid tumors that have worsened after standard treatments or when no beneficial standard treatment exists. Participants must be able to consent, follow study procedures, and use contraception. They should have measurable disease, good organ function, an ECOG status of 0-1, and recovered from previous therapy side effects.

Inclusion Criteria

You agree to sign a form saying you understand and agree to take part in the study, and you are able to follow all the study rules.

You agree to follow the specific birth control rules for the study treatment.

My cancer has spread and worsened despite all standard treatments.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive PTX-912 via IV infusion every 2 weeks until disease progression, unacceptable toxicity, or 12 months of total study therapy

Up to 12 months

Bi-weekly visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• PTX-912

Trial Overview PTX-912 is being tested in this Phase I trial to see if it's safe at different doses for patients with advanced solid tumors. It involves giving PTX-912 through an IV every two weeks until the disease progresses, side effects become too severe, or up to a maximum of 12 months.

Participant Groups

Group I: PTX-912 Experimental Treatment 1 Intervention

Single or multiple ascending dose of PTX-912

Who Is Running the Clinical Trial?

Proviva Therapeutics, Inc.

Lead Sponsor

Trials

1

Recruited

30+

Findings from Research

The IL18-IL2 fusion protein was successfully created and shown to significantly enhance IFN-γ production in immune cells, indicating its potential effectiveness in boosting the immune response against tumors.

In mouse models of various cancers, IL18-IL2 led to significant tumor regression, outperforming the effects of IL-18 and IL-2 used separately, suggesting it could be a promising candidate for cancer immunotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Human IL18-IL2 fusion protein as a potential antitumor reagent by enhancing NK cell cytotoxicity and IFN-γ production. Du, G., Ye, L., Zhang, G., et al.[2021]

The study developed a smaller fusion protein combining an erbB2-targeting antibody and interleukin 2 (IL-2), which retains the functions of both components and may enhance tumor targeting and immune response.

This scFv-Fc-IL-2 fusion protein, weighing only 66 kDa, could offer better penetration and pharmacokinetics compared to larger antibody-IL-2 fusion proteins, potentially improving the effectiveness of immunotherapy for erbB2-overexpressing tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A recombinant anti-erbB2, scFv-Fc-IL-2 fusion protein retains antigen specificity and cytokine function. Shi, M., Xie, Z., Feng, J., et al.[2019]

The huKS1/4-IL-2 fusion protein effectively targets IL-2 to the tumor microenvironment, leading to the complete eradication of established colon cancer metastases in mice, as evidenced by the absence of detectable tumor cells and a tripling of lifespan.

The antitumor effect is specifically mediated by CD8+ T cells, as the therapy was ineffective in T cell-deficient mice, highlighting the importance of a T cell-dependent immune response in combating cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Elimination of established murine colon carcinoma metastases by antibody-interleukin 2 fusion protein therapy. Xiang, R., Lode, HN., Dolman, CS., et al.[2016]

The antibody-cytokine fusion protein ch14.18-IL-2 effectively eradicated established melanoma metastases in mice and provided protective immunity against future tumor challenges, indicating its potential as a powerful cancer immunotherapy.

In a neuroblastoma model, targeted IL-2 enhanced a previously weak immune response, suggesting that this approach can strengthen the effects of other cancer treatments, linking T cell activation to improved clinical outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeted cytokines for cancer immunotherapy. Lode, HN., Reisfeld, RA.[2018]

BHK-21 cells producing a human IgG-IL2 fusion protein maintained stable productivity and intracellular ATP levels even under low nutrient conditions, indicating an efficient metabolic adaptation over an 80-day growth period.

The quality of the recombinant protein, specifically its oligosaccharide structures, remained consistent across different metabolic states, suggesting that the production process can be optimized without compromising product quality.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Metabolic shifts do not influence the glycosylation patterns of a recombinant fusion protein expressed in BHK cells. Cruz, HJ., Peixoto, CM., Nimtz, M., et al.[2019]

In a phase II trial involving 41 patients with advanced relapsed nonsmall cell lung cancer (NSCLC), denileukin diftitox showed limited efficacy, with only 44% achieving stable disease and a median survival of 5.8 months.

The treatment was associated with significant safety concerns, including one death from myocarditis and multiple instances of grade 3 toxicities, indicating that while it may stabilize disease, the risks may outweigh the benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Phase II trial of Denileukin Diftitox in patients with previously treated advanced non-small cell lung cancer. Gerena-Lewis, M., Crawford, J., Bonomi, P., et al.[2021]

The ch14.18-IL2 fusion protein specifically binds to GD2-positive melanoma and neuroblastoma cells, effectively delivering interleukin-2 (IL2) to stimulate immune cell proliferation both in healthy individuals and cancer patients.

This fusion protein not only enhances the immune response through localized IL2 delivery but also promotes antibody-dependent cellular cytotoxicity, indicating its potential as a promising treatment for GD2-positive tumors in upcoming clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Activation of human effector cells by a tumor reactive recombinant anti-ganglioside GD2 interleukin-2 fusion protein (ch14.18-IL2). Hank, JA., Surfus, JE., Gan, J., et al.[2007]

The new recombinant fusion protein OMCP-mutIL-2 selectively activates immune responses in natural killer (NK) cells without triggering harmful effects on regulatory T cells or causing severe side effects like capillary leak syndrome, which are common with traditional IL-2 therapy.

In mouse models, OMCP-mutIL-2 demonstrated superior tumor control compared to standard IL-2, indicating its potential as a safer and more effective immunotherapy for cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Selective targeting of IL-2 to NKG2D bearing cells for improved immunotherapy. Ghasemi, R., Lazear, E., Wang, X., et al.[2021]

Interleukin 2 (IL-2) has been pivotal in cancer immunotherapy, leading to FDA approval for treating metastatic renal cell carcinoma and melanoma, but it can cause significant side effects, including life-threatening conditions like vascular leak syndrome.

Research over the past 30 years has focused on improving IL-2 therapy by engineering methods to target IL-2 more effectively to tumors and enhance its action on immune cells, aiming to reduce toxicities while maintaining efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Interleukin 2-Based Fusion Proteins for the Treatment of Cancer. MacDonald, A., Wu, TC., Hung, CF.[2022]

A novel fusion protein was developed that combines an antibody fragment targeting the erbB-2 oncogene with the B7-2 costimulatory molecule, effectively triggering a T-cell response against tumors that overexpress erbB-2, which is found in 30% to 50% of breast cancers.

This fusion protein successfully binds to both tumor cells and T cells, suggesting it could enhance cancer immunotherapy by specifically targeting tumors and activating the immune response, warranting further in vivo studies for efficacy and distribution.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Engineering and characterization of a novel fusion protein incorporating B7.2 and an anti-ErbB-2 single-chain antibody fragment for the activation of Jurkat T cells. Marshall, KW., Marks, JD.[2019]

References

1. Germany pubmed.ncbi.nlm.nih.gov

Human IL18-IL2 fusion protein as a potential antitumor reagent by enhancing NK cell cytotoxicity and IFN-γ production. [2021]

2. Netherlands pubmed.ncbi.nlm.nih.gov

A recombinant anti-erbB2, scFv-Fc-IL-2 fusion protein retains antigen specificity and cytokine function. [2019]

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

Elimination of established murine colon carcinoma metastases by antibody-interleukin 2 fusion protein therapy. [2016]

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

Targeted cytokines for cancer immunotherapy. [2018]

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

Metabolic shifts do not influence the glycosylation patterns of a recombinant fusion protein expressed in BHK cells. [2019]

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

A Phase II trial of Denileukin Diftitox in patients with previously treated advanced non-small cell lung cancer. [2021]

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

Activation of human effector cells by a tumor reactive recombinant anti-ganglioside GD2 interleukin-2 fusion protein (ch14.18-IL2). [2007]

8. England pubmed.ncbi.nlm.nih.gov

Selective targeting of IL-2 to NKG2D bearing cells for improved immunotherapy. [2021]

9. Egypt pubmed.ncbi.nlm.nih.gov

Interleukin 2-Based Fusion Proteins for the Treatment of Cancer. [2022]

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

Engineering and characterization of a novel fusion protein incorporating B7.2 and an anti-ErbB-2 single-chain antibody fragment for the activation of Jurkat T cells. [2019]