68 Participants Needed

PTT-936 for Solid Tumors

Recruiting at 2 trial locations
Age: 18+
Sex: Any
Trial Phase: Phase 1 & 2
Sponsor: Pyrotech Therapeutics, Inc.
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)

Trial Summary

What is the purpose of this trial?

This trial is testing a new drug called PTT-936, which helps activate a protein to control tumor growth. It targets patients with advanced or spreading tumors. The drug may work better when combined with another treatment that boosts the immune system.

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 patients on therapeutic anticoagulation must be on a stable dose for at least 14 days before starting the trial, which suggests some medications may need to be managed carefully.

What data supports the effectiveness of the drug PTT-936 for solid tumors?

Research shows that anti-PD-1/PD-L1 therapies, like those combined with PTT-936, have been effective in treating certain types of lung cancer by helping the immune system attack cancer cells. Additionally, similar treatments have shown promise in overcoming resistance to other cancer drugs, suggesting potential benefits for solid tumors.12345

What safety information is available for PTT-936 and related therapies?

The safety of therapies targeting the PD-1/PD-L1 pathway, which may include PTT-936, has been studied in various cancers. Common side effects are related to the immune system, affecting the skin and digestive system, but they are usually mild and manageable. Serious side effects, like autoimmune conditions, can occur but are less common.678910

What makes the drug PTT-936 unique for treating solid tumors?

PTT-936 is unique because it combines an ALPK1 activator with anti-PD-1/L1 therapy, potentially enhancing the immune system's ability to fight tumors by targeting specific pathways that help cancer cells evade immune detection.2451112

Eligibility Criteria

Adults over 18 with advanced solid tumors that can't be surgically removed or have spread, who are able to follow the study plan. They should not need constant blood cell growth support and must have a life expectancy of at least 3 months. Their physical condition should allow normal activity or light work.

Inclusion Criteria

Ability and willingness to adhere to all study procedures
Life expectancy ≥ 3 months
Voluntarily signed informed consent form (ICF)
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Exclusion Criteria

I have cancer that has spread to the lining of my brain or spinal cord or new brain tumors.
I have had cancer other than the one being studied, but it has been in remission for over 3 years.
I haven't had major surgery or trauma in the last 4 weeks and don't expect any during the study.
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Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase 1 Treatment

Determining the pharmaceutically active dosage range and evaluating the safety profile of PTT-936 as a monotherapy

8-12 weeks
Weekly visits for PTT-936 administration

Phase 2a Treatment

Assessing the safety and efficacy of PTT-936 combined with anti-PD-1/L1 therapy

12-16 weeks
Weekly visits for PTT-936 and every three weeks for anti-PD-1/L1 therapy

Follow-up

Participants are monitored for safety and effectiveness after treatment

4-8 weeks

Treatment Details

Interventions

  • Combination of PTT-936 and anti-PD-1/L1 therapy
  • PTT-936
Trial OverviewThe trial is testing PTT-936 alone or combined with anti-PD-1/L1 therapy in two phases. Phase 1 finds the right dose and checks safety when used alone, while Phase 2a tests its effectiveness and safety when combined with anti-PD-1/L1 therapy against tumor growth.
Participant Groups
6Treatment groups
Experimental Treatment
Group I: PTT-936 and anti-PD-1/L1 combination therapyExperimental Treatment1 Intervention
PTT-936 will be administered once a week (QW) in combination with a standard-of-care (SOC) regimen of an anti-PD-1/L1 agent every three weeks (Q3W)
Group II: PTT-936 Dose Level 5Experimental Treatment1 Intervention
PTT-936 will be administered once a week (QW)
Group III: PTT-936 Dose Level 4Experimental Treatment1 Intervention
PTT-936 will be administered once a week (QW)
Group IV: PTT-936 Dose Level 3Experimental Treatment1 Intervention
PTT-936 will be administered once a week (QW)
Group V: PTT-936 Dose Level 2Experimental Treatment1 Intervention
PTT-936 will be administered once a week (QW)
Group VI: PTT-936 Dose Level 1Experimental Treatment1 Intervention
PTT-936 will be administered once a week (QW)

Find a Clinic Near You

Who Is Running the Clinical Trial?

Pyrotech Therapeutics, Inc.

Lead Sponsor

Trials
1
Recruited
70+

Findings from Research

Lung adenocarcinoma patients with the EML4-ALK fusion gene show higher PD-L1 protein expression, which is linked to poorer survival outcomes after treatment with crizotinib, indicating that PD-L1 may play a role in resistance to therapy.
The study suggests that ALK translocation increases PD-L1 expression through the activation of ERK, STAT3, and AKT pathways, proposing that combining ALK inhibitors with PD-L1-targeted therapies could improve treatment strategies for these patients.
PD-L1 Expression and Its Regulation in Lung Adenocarcinoma with ALK Translocation.Ma, L., Lv, J., Dong, Y., et al.[2019]
In a phase II study of 39 patients with advanced non-small cell lung cancer (NS-NSCLC) and high PD-L1 expression, the combination of atezolizumab and bevacizumab resulted in a promising objective response rate of 64.1%, indicating significant efficacy in this patient population.
The treatment showed a 12-month progression-free survival rate of 54.9% and an overall survival rate of 70.6%, with manageable safety profiles, as no patients experienced severe toxicity (grade 4/5), although some did experience serious adverse events.
Phase II study of atezolizumab with bevacizumab for non-squamous non-small cell lung cancer with high PD-L1 expression (@Be Study).Seto, T., Nosaki, K., Shimokawa, M., et al.[2022]
PF-06463922 is a next-generation ALK inhibitor that shows significantly higher potency than crizotinib against various ALK mutations, including those that confer resistance, such as F1174L and F1245C.
In preclinical studies, PF-06463922 induced complete tumor regression in both crizotinib-resistant and sensitive neuroblastoma models, suggesting it could be a promising treatment option for children with ALK-mutated neuroblastoma.
The ALK/ROS1 Inhibitor PF-06463922 Overcomes Primary Resistance to Crizotinib in ALK-Driven Neuroblastoma.Infarinato, NR., Park, JH., Krytska, K., et al.[2022]

References

PD-L1 Expression and Its Regulation in Lung Adenocarcinoma with ALK Translocation. [2019]
Phase II study of atezolizumab with bevacizumab for non-squamous non-small cell lung cancer with high PD-L1 expression (@Be Study). [2022]
The ALK/ROS1 Inhibitor PF-06463922 Overcomes Primary Resistance to Crizotinib in ALK-Driven Neuroblastoma. [2022]
Alterations in PD-L1 Expression Associated with Acquisition of Resistance to ALK Inhibitors in ALK-Rearranged Lung Cancer. [2020]
Upregulation of PD-L1 by EML4-ALK fusion protein mediates the immune escape in ALK positive NSCLC: Implication for optional anti-PD-1/PD-L1 immune therapy for ALK-TKIs sensitive and resistant NSCLC patients. [2022]
Toxicities of the anti-PD-1 and anti-PD-L1 immune checkpoint antibodies. [2023]
Toxicity management with combination chemotherapy and programmed death 1/programmed death ligand 1 inhibitor therapy in advanced lung cancer. [2020]
Clinical evaluation of compounds targeting PD-1/PD-L1 pathway for cancer immunotherapy. [2022]
Severe autoimmune-mediated thrombocytopenia in an elderly woman. [2022]
PD-1 as an emerging therapeutic target in renal cell carcinoma: current evidence. [2021]
11.United Statespubmed.ncbi.nlm.nih.gov
Response to treatment with an ALK-TKI in a patient with advanced lung adenocarcinoma with concurrent ALK fusion and high PD-L1 expression: A case report. [2023]
12.United Statespubmed.ncbi.nlm.nih.gov
Induction of PD-L1 Expression by the EML4-ALK Oncoprotein and Downstream Signaling Pathways in Non-Small Cell Lung Cancer. [2022]