PTT-936 for Solid Tumors

Recruiting at 2 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Pyrotech Therapeutics, Inc.

Disqualifiers: Brain metastases, Autoimmune disease, Cardiovascular events, others

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

Compensation: Varies

Number of Visits: 1872

68 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called PTT-936 for individuals with advanced or spreading solid tumors. It evaluates the safety and effectiveness of PTT-936, both alone and in combination with anti-PD-1/L1 therapy, which aids the immune system in fighting cancer. The primary goal is to assess the treatment's impact on tumor growth and patient response. Individuals with advanced solid tumors that cannot be surgically removed or have spread may be suitable for this study. As a Phase 1 trial, this research aims to understand how PTT-936 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 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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that PTT-936, a new treatment under study, is in the early testing stages to assess its safety and tolerability. The primary goal is to determine a dose that is both safe and effective. As testing continues, detailed safety information is not yet available, so a complete picture of PTT-936's safety remains incomplete.

Researchers are also examining how PTT-936 interacts with another cancer treatment called anti-PD-1/L1 therapy. These therapies are already used in other cancer treatments and have established safety profiles. However, their interaction with PTT-936 is still under investigation.

Participants should understand that, as this treatment is in the early testing phase, researchers are still learning about its safety and potential side effects. This is a normal part of developing any new treatment. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about PTT-936 for solid tumors because it offers a novel approach to cancer treatment. Unlike standard therapies that typically target specific proteins or pathways, PTT-936 may work by engaging the immune system in a unique way. When combined with anti-PD-1/L1 therapy, it could potentially enhance the body's immune response against cancer cells more effectively than current treatments alone. This combination could lead to improved outcomes for patients with solid tumors, offering a promising new option alongside existing therapies.

What evidence suggests that this trial's treatments could be effective for solid tumors?

Research has shown that PTT-936, one of the treatments in this trial, activates a protein called Alpha Kinase 1 (ALPK1), which helps control tumor growth. This is particularly important for patients with advanced or spreading solid tumors. Early results suggest that activating ALPK1 can slow tumor growth and improve patient response to treatment.

Another treatment arm in this trial combines PTT-936 with anti-PD-1/L1 therapy, which aids the immune system in fighting cancer cells. Anti-PD-1/L1 therapies alone benefit some patients, but usually fewer than 20% see a benefit. By adding PTT-936, researchers aim to increase the number of patients who benefit from the treatment. ^{1 2 3 4 5}

Are You a Good Fit for This Trial?

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)

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Combination of PTT-936 and anti-PD-1/L1 therapy
• PTT-936

Trial Overview The 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.

How Is the Trial Designed?

Group I: PTT-936 and anti-PD-1/L1 combination therapy Experimental Treatment 1 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 5 Experimental Treatment 1 Intervention

PTT-936 will be administered once a week (QW)

Group III: PTT-936 Dose Level 4 Experimental Treatment 1 Intervention

PTT-936 will be administered once a week (QW)

Group IV: PTT-936 Dose Level 3 Experimental Treatment 1 Intervention

PTT-936 will be administered once a week (QW)

Group V: PTT-936 Dose Level 2 Experimental Treatment 1 Intervention

PTT-936 will be administered once a week (QW)

Group VI: PTT-936 Dose Level 1 Experimental Treatment 1 Intervention

PTT-936 will be administered once a week (QW)

Who Is Running the Clinical Trial?

Pyrotech Therapeutics, Inc.

Lead Sponsor

Trials

1

Recruited

70+

Published Research Related to This Trial

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.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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]

In ALK-positive non-small cell lung cancer (NSCLC), resistance to ALK inhibitors is associated with increased levels of PD-L1 expression, suggesting a potential mechanism for immune evasion.

The study found that PD-L1 expression was significantly higher in ALK inhibitor-resistant cell lines and tumors from patients who had previously been treated with ALK inhibitors, indicating that targeting the PD-L1 pathway may be important in managing resistance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Alterations in PD-L1 Expression Associated with Acquisition of Resistance to ALK Inhibitors in ALK-Rearranged Lung Cancer. Kim, SJ., Kim, S., Kim, DW., et al.[2020]

The study found that ALK fusion proteins in non-small-cell lung cancer (NSCLC) increase PD-L1 expression, which can suppress T cell activity, indicating a mechanism of immune evasion in tumors.

ALK-TKIs not only reduce tumor viability but also enhance immune response by lowering PD-L1 levels, suggesting that while anti-PD-1 therapies may be effective, combining them with ALK-TKIs requires further investigation before clinical use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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. Hong, S., Chen, N., Fang, W., et al.[2022]

Immune checkpoint antibodies targeting the PD-1/PD-L1 pathway have shown significant antitumor activity and have been approved for use as single-agent therapies in metastatic malignant melanoma and nonsmall-cell lung cancer.

Understanding the toxicities associated with PD-1/PD-L1 blockade and having effective management strategies is crucial for maximizing both the safety and efficacy of these treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Toxicities of the anti-PD-1 and anti-PD-L1 immune checkpoint antibodies. Naidoo, J., Page, DB., Li, BT., et al.[2023]

Blocking the programmed death-1 receptor on T-cells with monoclonal antibodies has shown promising results in shrinking tumors and extending survival in cancers like melanoma and lung cancer, with response rates exceeding 20% in clinical trials.

While immune-related side effects are common, they are generally low grade and manageable, primarily affecting the skin and gastrointestinal tract, allowing for effective treatment strategies to be developed for these adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical evaluation of compounds targeting PD-1/PD-L1 pathway for cancer immunotherapy. Lu, J., Lee-Gabel, L., Nadeau, MC., et al.[2022]

A 34-year-old woman with stage IV lung adenocarcinoma was found to have both ALK fusion and high PD-L1 expression (80%), which is unusual as high PD-L1 levels rarely overlap with driver oncogenes like ALK.

Despite receiving targeted therapies like alectinib and combinations of ensatinib and dabrafenib, the patient's overall survival was only 10 months, indicating that non-small cell lung cancer with both ALK fusion and high PD-L1 expression may respond poorly to current treatments.

NCBI (Pubmed)

pubmed.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. Zhang, Y., Fang, H., Hong, J., et al.[2023]

Combining anti-PD-1 or anti-PD-L1 immunotherapy with platinum-based chemotherapy significantly improves outcomes for patients with advanced non-small-cell lung cancer (NSCLC) and small-cell lung cancer (SCLC), based on a systematic review of 9 randomized studies.

While immune-mediated adverse events (AEs) and infusion reactions were more common with the combination therapy, there were no unexpected toxicities, indicating that the treatment is generally safe and manageable with appropriate monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Toxicity management with combination chemotherapy and programmed death 1/programmed death ligand 1 inhibitor therapy in advanced lung cancer. Hoffner, B., Leighl, NB., Davies, M.[2020]

Anti-PD-1 immunotherapy, specifically pembrolizumab, has shown efficacy in reactivating the immune response against lung cancer, as evidenced by its use in an 80-year-old woman with primary lung adenocarcinoma.

However, this treatment can lead to significant immune-related adverse effects, such as serious autoimmune-mediated thrombocytopenia, highlighting the need for careful monitoring of patients undergoing anti-PD-1 therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Severe autoimmune-mediated thrombocytopenia in an elderly woman. Wei, M., Ding, H., Wang, Y.[2022]

High-dose interleukin-2 remains a first-line treatment for select patients with metastatic renal cell carcinoma (RCC), showing durable complete remissions in a small percentage of cases, despite RCC's poor response to conventional chemotherapy.

Monoclonal antibodies targeting PD-1 and PD-L1 have shown promising antitumor effects in clinical trials for refractory metastatic RCC, indicating a potential new avenue for effective immunotherapy in this challenging cancer type.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

PD-1 as an emerging therapeutic target in renal cell carcinoma: current evidence. Tykodi, SS.[2021]

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.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

PD-L1 Expression and Its Regulation in Lung Adenocarcinoma with ALK Translocation. Ma, L., Lv, J., Dong, Y., et al.[2019]

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.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The ALK/ROS1 Inhibitor PF-06463922 Overcomes Primary Resistance to Crizotinib in ALK-Driven Neuroblastoma. Infarinato, NR., Park, JH., Krytska, K., et al.[2022]

In non-small cell lung cancer (NSCLC) with the EML4-ALK fusion gene, PD-L1 expression is significantly higher, suggesting that this genetic alteration may enhance the cancer's ability to evade the immune system.

The study found that inhibiting the ALK pathway with alectinib or targeting the MEK-ERK and PI3K-AKT signaling pathways can reduce PD-L1 expression, indicating potential therapeutic strategies to improve immune response against NSCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Induction of PD-L1 Expression by the EML4-ALK Oncoprotein and Downstream Signaling Pathways in Non-Small Cell Lung Cancer. Ota, K., Azuma, K., Kawahara, A., et al.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06244992

PTT-936 Alone or in Combination in Patients With Locally ... This Phase 1/2a study will explore the safety and efficacy of PTT-936, an Alpha Kinase 1 (ALPK1) activator, used alone or in combination with anti-PD-1/L1 ...

2. mayo.edu mayo.edu/research/clinical-trials/cls-20567685

PTT-936, an Alpha Kinase 1 (ALPK1) Activator, Alone or in ... The primary objective of this study is to evaluate the safety and tolerability of a pharmacologically active dose (PAD) range of PTT-936.

3. aging.networkofcare.org aging.networkofcare.org/sanmateo/CommunityResources/ClinicalTrials/Detail/NCT06244992?keyword=%22Locally%20Advanced%20or%22

San Mateo Clinical Trial PTT-936 Alone or in Combination ... This Phase 1/2a study will explore the safety and efficacy of PTT-936, an Alpha Kinase 1 (ALPK1) activator, used alone or in combination with anti-PD-1/L1 ...

4. synapse.patsnap.com synapse.patsnap.com/drug/5a6543edbd4d4b15ac951be4d0df83df

PTT-936 - Drug Targets, Indications, Patents 一项在局部晚期或转移性实体瘤患者中评价PTT-936（一种α激酶1[ALPK1]激动剂）单药治疗或与PD-1/L1抗体联合治疗的安全性、药代动力学和有效性的I/IIa期研究.

5. withpower.com withpower.com/trial/phase-2-neoplasms-2024-82a5a

PTT-936 for Solid Tumors 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.