PT199 + Anti-PD-1 for Cancer
Recruiting in Palo Alto (17 mi)
+5 other locations
Age: 18+
Sex: Any
Travel: May be covered
Time Reimbursement: Varies
Trial Phase: Phase 1 & 2
Recruiting
Sponsor: Phanes Therapeutics
No Placebo Group
Breakthrough Therapy
Trial Summary
What is the purpose of this trial?This trial tests a new drug, PT199, which helps the immune system fight advanced cancers that haven't responded to other treatments. PT199 blocks a protein that helps cancer cells hide, making it easier for the immune system to attack them, especially when combined with other immune-boosting drugs.
Will I have to stop taking my current medications?
The trial protocol does not specify if you must stop taking your current medications. However, you cannot participate if you are currently on corticosteroids or other immunosuppressive medications within 14 days before the study, or if you are taking certain anticoagulants like warfarin within 5 days before starting the trial.
What data supports the effectiveness of the drug PT199 + Anti-PD-1 for cancer?
Research shows that drugs blocking PD-1, like Anti-PD-1 antibodies, improve survival in patients with advanced melanoma and other solid tumors. These drugs are often combined with other treatments in numerous clinical trials, suggesting they have broad potential in cancer therapy.
12345What safety information is available for PT199 and Anti-PD-1 treatments?
Anti-PD-1 treatments, used in cancer therapy, can cause side effects like skin issues and digestive problems, which are usually mild and manageable. They can also lead to immune-related side effects affecting the thyroid and other organs, but these are typically low grade and resolve with proper care.
678910What makes the drug PT199 + Anti-PD-1 unique for cancer treatment?
The drug PT199 + Anti-PD-1 is unique because it combines PD-1 inhibitors, which help the immune system attack cancer cells, with PT199, an anti-CD73 monoclonal antibody, potentially enhancing the immune response against cancer. This combination may offer a novel approach compared to standard treatments that typically focus on a single target.
15111213Eligibility Criteria
This trial is for adults with advanced solid tumors that have worsened after standard treatments or when such treatments aren't suitable. Participants must have a performance status indicating they are fully active or restricted in physically strenuous activity but can do light work, and be able to provide tissue samples. Pregnant women, those with certain medical conditions, or who've had recent treatments excluded by the trial's criteria cannot participate.Inclusion Criteria
I can provide a tissue sample for cancer biomarker testing.
I am fully active or can carry out light work.
My biopsy was not just a needle aspiration.
Exclusion Criteria
I have been treated for an autoimmune disease in the last year.
I haven't had chemotherapy, targeted therapy, or immunotherapy in the last 4 weeks.
I am a woman who can have children and do not use birth control.
I do not have severe health issues like uncontrolled high triglycerides or infections that could make the trial unsafe for me.
I have had lung inflammation treated with steroids or have a lung condition.
I have severe nerve damage.
I haven't had major radiation in the last 4 weeks or small area radiation in the last 2 weeks.
I am not on warfarin or similar blood thinners, but other types are okay.
I am not pregnant or breastfeeding.
I am allergic to some cancer immunotherapy drugs or their ingredients.
I have not had T-cell, NK cell, or CD73 inhibitor therapy but may have had PD-1 or PD-L1 inhibitors.
I stopped immune therapy due to side effects.
Participant Groups
PT199 (an Anti-CD73 mAb) alone and combined with a PD-1 inhibitor are being tested in patients with advanced cancers. The study will assess safety, tolerability, how the body processes these drugs, their effects on the body and initial effectiveness against cancer progression.
4Treatment groups
Experimental Treatment
Group I: Part D: Chemotherapy CombinationExperimental Treatment7 Interventions
The Chemotherapy Combination Therapy Dose Escalation and Expansion will investigate four cohorts, one in frontline PDAC, two in frontline NSCLC and one in second-line and later NSCLC patients. Patients will receive Mavrostobart (PT199) plus chemotherapy, with one cohort also receiving pembrolizumab.
Group II: Part C: Combination Therapy Dose ExpansionExperimental Treatment2 Interventions
Two RDEs for Part C will be determined in Part B and will be further evaluated in two dose expansion cohorts. Patients will be treated with Mavrostobart (PT199) in combination with a PD-1 inhibitor, tislelizumab.
Group III: Part B: Combination Therapy Dose EscalationExperimental Treatment2 Interventions
A standard 3+3 dose escalation design will be employed, and 3 patients will be enrolled initially at each dose level. Patients will be treated with Mavrostobart (PT199) in combination with a PD-1 inhibitor, tislelizumab.
Group IV: Part A: Monotherapy Dose EscalationExperimental Treatment1 Intervention
A standard 3+3 dose escalation design will be employed, and 3 patients will be enrolled initially at each dose level. Mavrostobart (PT199) will be administered as a monotherapy.
Anti-PD-1 monoclonal antibody is already approved in United States, United States, European Union, European Union for the following indications:
🇺🇸 Approved in United States as Nivolumab (Opdivo) for:
- Melanoma
- Non-small cell lung cancer
- Renal cell carcinoma
- Hodgkin lymphoma
- Head and neck squamous cell carcinoma
- Urothelial carcinoma
- Colorectal cancer
- Hepatocellular carcinoma
- Small cell lung cancer
- Esophageal squamous cell carcinoma
- Gastric cancer
- Gastroesophageal junction cancer
🇺🇸 Approved in United States as Pembrolizumab (Keytruda) for:
- Melanoma
- Non-small cell lung cancer
- Head and neck squamous cell carcinoma
- Urothelial carcinoma
- Colorectal cancer
- Hepatocellular carcinoma
- Small cell lung cancer
- Esophageal squamous cell carcinoma
- Gastric cancer
- Gastroesophageal junction cancer
- Cervical cancer
- Endometrial cancer
🇪🇺 Approved in European Union as Nivolumab (Opdivo) for:
- Melanoma
- Non-small cell lung cancer
- Renal cell carcinoma
- Hodgkin lymphoma
- Squamous cell carcinoma of the head and neck
- Urothelial carcinoma
- Colorectal cancer
- Hepatocellular carcinoma
- Small cell lung cancer
- Esophageal squamous cell carcinoma
- Gastric cancer
- Gastroesophageal junction cancer
🇪🇺 Approved in European Union as Pembrolizumab (Keytruda) for:
- Melanoma
- Non-small cell lung cancer
- Head and neck squamous cell carcinoma
- Urothelial carcinoma
- Colorectal cancer
- Hepatocellular carcinoma
- Small cell lung cancer
- Esophageal squamous cell carcinoma
- Gastric cancer
- Gastroesophageal junction cancer
- Cervical cancer
- Endometrial cancer
Find A Clinic Near You
Research locations nearbySelect from list below to view details:
SCRI Oncology PartnersNashville, TN
Sarah Cannon Research Institute University of OklahomaOklahoma City, OK
Tranquility ResearchWebster, TX
Carolina BioOncology InstituteHuntersville, NC
More Trial Locations
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Who is running the clinical trial?
Phanes TherapeuticsLead Sponsor
BeiGeneIndustry Sponsor
References
Discontinuation of anti-PD-1 antibody therapy in the absence of disease progression or treatment limiting toxicity: clinical outcomes in advanced melanoma. [2023]Programmed cell death protein 1 (PD-1) blocking monoclonal antibodies improve the overall survival of patients with advanced melanoma but the optimal duration of treatment has not been established.
Analysis of response rate with ANTI PD1/PD-L1 monoclonal antibodies in advanced solid tumors: a meta-analysis of randomized clinical trials. [2022]Anti-PD1/PD-L1 monoclonal antibodies (mAbs) increase overall survival compared to standard of care (SOC) in different tumors. However, a proportion of patients (pts) will have progressive disease (PD) as best response. We conducted a meta-analysis to study the rates of response comparing these antibodies with SOC.
Preclinical Characterization of GLS-010 (Zimberelimab), a Novel Fully Human Anti-PD-1 Therapeutic Monoclonal Antibody for Cancer. [2022]Zimberelimab (GLS-010) is a novel fully human monoclonal immunoglobulin G4 (IgG4) against the programmed cell death-1 (PD-1) receptor.
Combination therapy with PD-1/PD-L1 blockade: An overview of ongoing clinical trials. [2021]Monoclonal antibodies (mAbs) that block the programmed death 1 (PD-1) or programmed death-ligand 1 (PD-L1) receptors are the most clinically advanced tumor immunotherapies. Given the broad antitumor efficacy and novel mechanism of action, numerous combinatorial approaches incorporating PD-1/PD-L1 blockade have been suggested; herein we present a comprehensive analysis of these clinical trials. We queried clinicaltrials.gov for all PD-1/PD-L1 mAbs administered for cancer therapy with an end date of 4/30/2017. A total of 1,218 clinical trials met our search criteria. These trials have a planned enrollment of 227,190 patients, and approximately half (493) were initiated in 2016 alone. Of these over 1,200 trials, 916 combine PD-1/PD-L1 blockade with at least one additional therapy, ranging from traditional treatment modalities like surgery and chemoradiation to newer therapies like small molecule inhibitors and other immunotherapies. The staggering proliferation of clinical trials combining PD-1/PD-L1 blockade with disparate treatments necessitates careful accounting to maximize efficiency and highlight areas of unmet needs. We believe our analysis provides this data and expect it will facilitate the design of future clinical trials in this burgeoning area of oncology research.
(18)F-FDG PET/CT and Melanoma: Staging, Immune Modulation and Mutation-Targeted Therapy Assessment, and Prognosis. [2022]Monoclonal antibodies that target the programmed cell death 1 (PD-1) immune checkpoint protein and its associated ligands, PD-L1 and PD-L2, and targeted inhibitors of mutated signal transduction molecules such as BRAF inhibitors show immense promise in treating patients with melanoma. We discuss the use of (18)F-FDG PET/CT for assessing therapy effectiveness, staging advanced disease, and determining prognosis of patients with melanoma.
The incidence and relative risk of pulmonary toxicity in patients treated with anti-PD1/PD-L1 therapy for solid tumors: a meta-analysis of current studies. [2018]Monoclonal antibodies (mAbs) directed against PD-1/PD-L1 have recently entered the therapeutic algorithm of several solid tumors. Among treatment-related adverse events pulmonary toxicity (PT) is of particular interest. We assess the incidence and relative risk (RR) of PT in patients treated with anti-PD1/PD-L1 mAbs.
Clinical evaluation of compounds targeting PD-1/PD-L1 pathway for cancer immunotherapy. [2022]Significant enthusiasm currently exists for new immunotherapeutic strategies: blocking the interaction between programmed death-1 receptor on T-cells and programmed death-ligand 1 on tumor cells to boost immune system stimulation to fight cancer. Immunomodulation with the antiprogrammed death-1/programmed death-ligand 1 monoclonal antibodies has shown to mediate tumor shrinkage and extend overall survival from several pivotal phase I/II studies in melanoma, renal cell carcinoma, and non-small cell lung cancer. This has prompted multiple large ongoing phase III trials with the expectation for fast-track FDA approvals to satisfy unmet medical needs. Compounds targeting the programmed death-1 pathway that are in clinical trials fall into two major categories, namely antiprogrammed death-1 antibodies: Nivolumab, MK-3475, and pidilizumab; and antiprogrammed death-ligand 1 antibodies: MPDL3280A, BMS-936559, MEDI4736, and MSB0010718C. We reviewed the clinical efficacy and safety of each compound based upon major registered clinical trials and published clinical data. Overall, response rate of more than 20% is consistently seen across all these trials, with maximal response of approximately 50% achieved by certain single antiprogrammed death-1 agents or when used in combination with cytotoxic T-lymphocyte antigen-4 blockade. The responses seen are early, durable, and have continued after treatment discontinuation. Immune-related adverse events are the most common side effects seen in these clinical trials. Overall, the skin and gastrointestinal tract are the most common organ systems affected by these compounds while hepatic, endocrine, and neurologic events are less frequent. These side effects are low grade, manageable, and typically resolve within a relatively short time frame with a predictable resolution pattern given proper management. We therefore propose detailed guidelines for management of major immune-related adverse events that are anticipated with antiprogrammed death-1/programmed death-ligand 1 therapies based on general experience with other monoclonal antibodies and the established management algorithms for immune-related adverse events for cytotoxic T-lymphocyte antigen-4 blockade with ipilimumab. We anticipate that the antiprogrammed death-1 strategy will become a viable and crucial clinical strategy for cancer therapy.
Programmed cell death-1 and programmed cell death ligand-1 antibodies-induced dysthyroidism. [2020]Monoclonal antibodies blocking the programmed cell death-1 (PD-1) or its ligand (PD-L1) are a group of immune checkpoints inhibitors (ICIs) with proven antitumor efficacy. However, their use is complicated by immune-related adverse events (irAEs), including endocrine adverse events (eAEs).
Comparison of the toxicity profile of PD-1 versus PD-L1 inhibitors in non-small cell lung cancer: A systematic analysis of the literature. [2022]Monoclonal antibodies against programmed cell death protein 1 (PD-1) and programmed death ligand 1 (PD-L1) are effective therapies in patients with non-small cell lung cancer (NSCLC). Herein, the authors performed a systematic review investigating differences in the toxicities of PD-1 and PD-L1 inhibitors.
Monitoring and Management of Immune-Related Adverse Events Associated With Programmed Cell Death Protein-1 Axis Inhibitors in Lung Cancer. [2018]Monoclonal antibodies targeting programmed cell death protein-1 (PD-1) represent a new treatment paradigm in non-small cell lung cancer. Three phase III trials have demonstrated a survival benefit and improved tolerability of nivolumab and pembrolizumab when compared with standard second-line chemotherapy. Nevertheless, the adverse events associated with PD-1 inhibitors are unique; early recognition and treatment are essential. This review summarizes the required monitoring and appropriate management of immune-related adverse events in lung cancer patients receiving these agents.
A human receptor occupancy assay to measure anti-PD-1 binding in patients with prior anti-PD-1. [2022]Receptor occupancy (RO) assessment by flow cytometry is an important pharmacodynamic (PD) biomarker in the clinical development of large molecules such as monoclonal therapeutic antibodies (mAbs). The total-drug-bound RO assay format directly assesses mAb binding to cell surface targets using anti-drug detection antibodies. Here, we generated a flow cytometry detection antibody specifically binding to mAbs of the IgG1 P329GLALA backbone. Using this reagent, we developed a total-drug-bound RO assay format for RG7769, a bi-specific P329GLALA containing mAb targeting PD-1 and TIM3 on T cells. In its fit-for-purpose validated version, this RO assay has been used in the Phase-I dose escalation study of RG7769, informing on peripheral T cell RO and RG7769 antibody binding capacity (ABC). We assessed RG7769 RO in checkpoint-inhibitor (CPI) naïve patients and anti-PD-1 CPI experienced patients using our novel assay. Here, we show that in both groups, complete T cell RO can be achieved (~100%). However, we found that the maximum number of T cell binding sites for RG7769 pre-dosing was roughly twofold lower in patients recently having undergone anti-PD-1 treatment. We show that this is due to steric hindrance exerted by competing mAbs masking the available drug binding sites. Our findings highlight the importance of quantitative mAb assessment in addition to relative RO especially in the context of patients who have previously received anti-PD-1 treatment.
Successful Immunotherapy against a Transplantable Mouse Squamous Lung Carcinoma with Anti-PD-1 and Anti-CD137 Monoclonal Antibodies. [2021]Anti-programmed cell death 1 (anti-PD-1) and anti-programmed cell death ligand 1 (PD-L1) antagonist monoclonal antibodies (mAbs) against metastatic non-small cell lung cancer with special efficacy in patients with squamous cell lung cancer are being developed in the clinic. However, robust and reliable experimental models to test immunotherapeutic combinations in squamous lung tumors are still lacking.
Immune-Related Adverse Events Mimicking Behcet's Disease in a Gastric Cancer Patient Following Camrelizumab Treatment. [2021]Anti-programmed cell death 1(anti-PD-1) antibodies are immune checkpoint inhibitors (ICIs) used as a treatment option for a number of cancers to expand lifespan. However, the toxicity caused by ICIs is often unpredictable and can be occasionally life-threatening.