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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called PTX-912 (an IL-2 fusion protein) for individuals with advanced solid tumors that have worsened despite other treatments. The trial aims to determine the safety and tolerability of PTX-912, its behavior in the body, and its potential to combat tumors. Participants will receive PTX-912 through an IV every two weeks. Suitable candidates are those with solid tumors that have spread or are in advanced stages and lack other effective treatment options. As a Phase 1 trial, this research focuses on understanding how PTX-912 works in people, offering participants the opportunity to be among the first to receive this new treatment.

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.

Is there any evidence suggesting that PTX-912 is likely to be safe for humans?

Research has shown that PTX-912, a new cancer treatment, is safe in early studies. In one study with monkeys, PTX-912 was administered for four weeks and demonstrated excellent safety results without serious immune-related side effects. This suggests the treatment might be well-tolerated in humans.

As this trial is in an early phase, the main goal is to determine if PTX-912 is safe for people. Safety data in humans remains limited, but the positive findings in animals are encouraging and provide a basis for testing PTX-912 in people with solid tumors. Participants will receive increasing doses to identify the safest way to use it. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

PTX-912 is unique because it offers a new approach to treating cancer with its innovative mechanism of action. Unlike traditional chemotherapy, which targets rapidly dividing cells indiscriminately, PTX-912 is designed to specifically target and interfere with cancer cell growth, potentially reducing side effects and improving effectiveness. Researchers are excited about PTX-912 because it represents a targeted therapy approach, which may lead to more efficient cancer treatment with fewer adverse effects compared to existing options like chemotherapy and radiation.

What evidence suggests that PTX-912 might be an effective treatment for cancer?

Research has shown that PTX-912, which participants in this trial will receive, may help treat cancer by enhancing the immune system's ability to fight tumors. Early studies found that PTX-912, a special protein combining PD-1 and proIL-2, had strong effects against tumors without causing major side effects. In animal studies, it increased the number of key immune cells that attack tumors. Additionally, similar treatments that combine IL-2 with other cancer therapies have demonstrated high success rates in patients with certain cancers. These findings suggest PTX-912 could effectively treat solid tumors by boosting the body's natural defenses. ^{1 2 3 4 5}

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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 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]

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]

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]

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]

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]

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]

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]

Citations

1. jitc.bmj.com jitc.bmj.com/content/12/Suppl_2/A1083

967 PTX912, a first-in-class PD-1/proIL-2 fusion protein ... Conclusions Our preclinical data demonstrate that PTX-912 exhibits strong anti-tumor efficacy without causing significant peripheral toxicity in ...

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.TPS2694

A first-in-human (FIH) phase I study of PTX-912 in patients ... Moreover, combining IL-2 with pembrolizumab in mRCC demonstrated a durable response rate of 70%, compared to objective response rates (ORR) of ...

3. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.e14697

Effect of a novel anti-PD-1-proIL-2 bifunctional fusion ... Analysis of PTX-912 treated mice showed increased tumor infiltrating CD4+ and CD8+ T cells, including PD-1+Tcf-1+ and PD-1+ IL-18Ra+TIM3- CD8+ T ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S2095927325008096

Synergistic potential of PD-1 blockade and IL-2 in cancer ... Interleukin-2 (IL-2) shows promise in overcoming the limitations of PD-1 blockade therapy. · High-dose recombinant IL-2 demonstrates efficacy against metastatic ...

5. withpower.com withpower.com/trial/phase-1-neoplasm-metastasis-3-2024-a7b93

PTX-912 for Cancer The IL18-IL2 fusion protein was successfully created and shown to significantly enhance IFN-γ production in immune cells, indicating its potential effectiveness ...