ONC-392 + Pembrolizumab for Non-Small Cell Lung Cancer
(PRESERVE-001 Trial)
Recruiting in Palo Alto (17 mi)
+40 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 1 & 2
Recruiting
Sponsor: OncoC4, Inc.
Must not be taking: Chronic steroids
Disqualifiers: Active brain metastasis, Active infection, others
No Placebo Group
Breakthrough Therapy
Trial Summary
What is the purpose of this trial?This trial tests ONC-392, an antibody that helps the immune system fight cancer, in patients with advanced or spreading tumors who haven't responded to other treatments. It works by blocking a protein that usually keeps immune responses in check, making it easier for the body to attack cancer cells.
Will I have to stop taking my current medications?
The trial requires a washout period (time without taking certain medications) of 21 days for cancer therapeutic drugs and 28 days for antibody drugs. If you are on chronic systemic steroid therapy at doses greater than 10 mg/day, you may not be eligible to participate.
What data supports the effectiveness of the drug ONC-392 + Pembrolizumab for Non-Small Cell Lung Cancer?
Research shows that pembrolizumab, a part of the treatment, has been effective in improving survival rates for patients with advanced non-small cell lung cancer, especially those with high levels of a protein called PD-L1. This suggests that the combination with ONC-392 could also be promising.
12345What safety information is available for ONC-392 and Pembrolizumab in humans?
Pembrolizumab (also known as Keytruda) has been used in various clinical trials and is generally considered safe, but it can cause side effects like fatigue, cough, nausea, and more serious immune-related issues such as pneumonitis (lung inflammation). These side effects have been observed in patients with different types of cancer, including lung cancer and melanoma.
16789How is the drug ONC-392 + Pembrolizumab unique for treating non-small cell lung cancer?
The combination of ONC-392 and Pembrolizumab is unique because it pairs a novel agent, ONC-392, with Pembrolizumab, an established immune checkpoint inhibitor that blocks the PD-1 pathway, potentially enhancing the immune system's ability to fight cancer cells in non-small cell lung cancer.
15101112Eligibility Criteria
Adults over 18 with certain advanced solid tumors or NSCLC, who have measurable disease and are in good physical condition. They must not be on high-dose steroids, pregnant, breastfeeding, or have brain metastases. Participants need functioning organs and agree to use contraception.Inclusion Criteria
I am fully active or restricted in physically strenuous activity but can do light work.
I have an advanced cancer type that is treated with Pembrolizumab.
I am a woman who can have children and my pregnancy test is negative.
+9 more
Exclusion Criteria
I am on long-term steroid treatment with doses over 10 mg/day.
I have active brain or spinal cord cancer symptoms.
Patients who have a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the patient's participation for the full duration of the study, or is not in the best interest of the patient to participate, in the opinion of the treating Investigator
+6 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Dose-Finding Phase I (Part A)
ONC-392 is administered as a single agent to determine the recommended Phase II dose for monotherapy
21 days
Every 21 days (Q3W)
Combination Therapy Phase (Part B)
ONC-392 is administered in combination with pembrolizumab to determine the recommended Phase II dose for combination therapy
21 days
Every 21 days (Q3W)
Expansion Cohorts (Part C)
Further assessment of safety and efficacy of ONC-392 in various cancer cohorts
Varies by cohort
Phase II Study (Part D)
ONC-392 monotherapy in recurrent and/or metastatic adenoid cystic carcinoma
1 year
Follow-up
Participants are monitored for safety and effectiveness after treatment
1 year
Participant Groups
The trial is testing ONC-392 alone and combined with Pembrolizumab in patients with various cancers including NSCLC. It's a first-in-human study assessing safety, how the body processes the drug (pharmacokinetics), and effectiveness.
3Treatment groups
Experimental Treatment
Group I: ONC-392 in combination with pembrolizumabExperimental Treatment2 Interventions
The Part B1 study will test ONC-392 intravenous (IV) infusion, Q3W, in combination with fixed dose of pembrolizumab. The dose for pembrolizumab will be fixed at 200mg/cycle dosed every 21 days (Q3W).
The Part B1 will start at one level below RP2D-M dose for ONC-392 and 200mg of pembrolizumab. When 2 DLTs occur before 6 patients are enrolled, the ONC-392 dose will be decreased to the next dose level until ≤ 1/6 patients treated at that dose develops a DLT. This dose level will be designated RP2D-C.
In Part C, the expansion cohorts Arm D to G will assess the safety and efficacy of ONC-392 in different dose levels and Pembrolizumab combination therapy in non small cell lung cancer, and metastatic melanoma.
Group II: ONC-392 and docetaxelExperimental Treatment2 Interventions
Part E Arm O will test ONC-392 in combination with docetaxel, IV infusion, Q3W, in PD-1 resistant NSCLC patients.
Group III: ONC-392 Treatment as single agentExperimental Treatment1 Intervention
The Part A study will test ONC-392 intravenous (IV) infusion up to five predefined dose levels from 0.1 mg/kg to 10 mg/kg ONC-392 as monotherapy every 21 days (Q3W). The Part A study will determine the maximal tolerable dose (MTD) and the recommended Phase 2 dose in monotherapy (RP2D-M).
In Part C, Arms A-C, I-N monotherapy expansion cohorts will further assess the safety and efficacy of ONC-392 in different dose levels as monotherapy in pancreatic cancer, triple negative breast cancer, non small cell lung cancer with driver mutations, PD-1 resistant non small cell lung cancer, PD-1 resistant melanoma, head and neck cancer, ovarian cancer, renal cell carcinoma and other solid tumors.
Part D is a Phase II study on recurrent and/or metastatic adenoid cystic carcinoma.
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
University of Cincinnati Medical CenterCincinnati, OH
Tennessee Oncology - NashvilleNashville, TN
Zangmeister Cancer CenterColumbus, OH
Greater Baltimore Medical CenterBaltimore, MD
More Trial Locations
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Who Is Running the Clinical Trial?
OncoC4, Inc.Lead Sponsor
National Cancer Institute (NCI)Collaborator
References
Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. [2022]A phase II trial investigating the therapeutic effect of neoadjuvant programmed cell death 1 (PD-1) inhibitor pembrolizumab (MK-3475, KEYTRUDA®) administered prior to surgery for the treatment of non-small cell lung cancer (NSCLC) has been conducted (NCT03197467). We report the first clinical results of a planned interim safety analysis after 15 patients were enrolled.
Augmenting Real-World Data Through Modeling Key Clinical Trial Eligibility Criteria: An Example of Patients With Non-small-Cell Lung Cancer Treated With Pembrolizumab. [2021]To compare and characterize baseline characteristics and overall survival (OS) differences by key oncology eligibility criteria for real-world patients from the Flatiron Health database with advanced non-small-cell lung cancer (NSCLC) who received pembrolizumab monotherapy.
Long-Term Real-World Outcomes of First-Line Pembrolizumab Monotherapy for Metastatic Non-Small Cell Lung Cancer With ≥50% Expression of Programmed Cell Death-Ligand 1. [2022]Immune checkpoint inhibitors (ICIs) of programmed cell death 1/programmed cell death ligand 1 (PD-1/PD-L1) have been rapidly adopted in US clinical practice for first-line therapy of metastatic non-small cell lung cancer (NSCLC) since regulatory approval in October 2016, and a better understanding is needed of long-term outcomes of ICI therapy administered in real-world settings outside of clinical trials. Our aim was to describe long-term outcomes of first-line pembrolizumab monotherapy at US oncology practices for patients with metastatic NSCLC, PD-L1 expression ≥50%, and good performance status.
Updated Analysis of KEYNOTE-024: Pembrolizumab Versus Platinum-Based Chemotherapy for Advanced Non-Small-Cell Lung Cancer With PD-L1 Tumor Proportion Score of 50% or Greater. [2022]In the randomized, open-label, phase III KEYNOTE-024 study, pembrolizumab significantly improved progression-free survival and overall survival (OS) compared with platinum-based chemotherapy in patients with previously untreated advanced non-small-cell lung cancer (NSCLC) with a programmed death ligand 1 tumor proportion score of 50% or greater and without EGFR/ALK aberrations. We report an updated OS and tolerability analysis, including analyses adjusting for potential bias introduced by crossover from chemotherapy to pembrolizumab.
[Prolonged response with paclitaxel after immunotherapy by pembrolizumab in lung cancer]. [2017]Pembrolizumab, a humanized monoclonal antibody IgG4 anti-PD-1, having offered promising results in patients suffering from non-small cell lung cancer metastatic and heavily pretreated.
FDA Approval Summary: Accelerated Approval of Pembrolizumab for Second-Line Treatment of Metastatic Melanoma. [2021]On September 4, 2014, the FDA approved pembrolizumab (KEYTRUDA; Merck Sharp & Dohme Corp.) with a recommended dose of 2 mg/kg every 3 weeks by intravenous infusion for the treatment of patients with unresectable or metastatic melanoma who have progressed following treatment with ipilimumab and, if BRAF V600 mutation positive, a BRAF inhibitor. Approval was based on demonstration of objective tumor responses with prolonged response durations in 89 patients enrolled in a randomized, multicenter, open-label, dose-finding, and activity-estimating phase 1 trial. The overall response rate (ORR) by blinded independent central review per RECIST v1.1 was 24% (95% confidence interval, 15-34); with 6 months of follow-up, 86% of responses were ongoing. The most common (≥20%) adverse reactions were fatigue, cough, nausea, pruritus, rash, decreased appetite, constipation, arthralgia, and diarrhea. Immune-mediated adverse reactions included pneumonitis, colitis, hepatitis, hypophysitis, and thyroid disorders. The benefits of the observed ORR with prolonged duration of responses outweighed the risks of immune-mediated adverse reactions in this life-threatening disease and represented an improvement over available therapy. Important regulatory issues in this application were role of durability of response in the evaluation of ORR for accelerated approval, reliance on data from a first-in-human trial, and strategies for dose selection. Clin Cancer Res; 23(19); 5666-70. ©2017 AACR.
Recurrent and atypical immune checkpoint inhibitor-induced pneumonitis. [2023]Pembrolizumab (Keytruda) is a monoclonal antibody against the programmed cell death-1 (PD-1) receptor on lymphocytes, which is one of the immune checkpoint inhibitors (ICIs) approved for multiple solid and hematologic malignancies. Although ICIs have proven to be more effective and less toxic compared to chemotherapy, there are reports of adverse side effects with ICIs. For example, pneumonitis is a potentially lethal side effect occurring in 1%-5% of patients who received ICIs in clinical trials, and there are case reports with clinical and radiological features of checkpoint inhibitor-pneumonitis (CIP).
FDA Approves Pembrolizumab for BCG-Unresponsive NMIBC. [2021]The FDA approved pembrolizumab (Keytruda) for the treatment of patients with Bacillus Calmette-Guerin (BCG)-unresponsive, high-risk, non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS) with or without papillary tumors who are ineligible for or chose to not undergo cystectomy.
Pembrolizumab for the treatment of thoracic malignancies: current landscape and future directions. [2017]New insights into the interaction between the immune system and the tumor microenvironment have led to the development of checkpoint inhibitors that target the PD-1/PD-L1 pathway. Pembrolizumab (MK-3475, lambrolizumab, Keytruda(®)) is a PD-1 inhibitor that has shown clinical activity in a variety of solid tumors and is currently approved for the second-line treatment of PD-L1-positive non-small-cell lung cancer and for unresectable/metastatic melanoma. This article will discuss the results of early-phase trials of pembrolizumab in thoracic malignancies as well as ongoing studies aimed to confirm clinical benefit.
Characterization of the tumor immune-microenvironment of adenocarcinoma of lung with a metastatic lesion in the pancreas treated successfully with first-line, single-agent pembrolizumab. [2023]Single-agent immune checkpoint inhibitor therapy in advanced non-small cell lung cancer can significantly prolong progression-free and overall survival when compared with cytotoxic chemotherapy. Here, we report a case of newly diagnosed adenocarcinoma of the lung with a solitary brain metastasis and a biopsy confirmed adenocarcinoma in the tail of the pancreas. Cytomorphology and immunohistochemistry suggested the lung and pancreas tumors were distinct primaries. However, molecular analysis of the lung primary and tumor in the pancreas revealed the same mutations of functional significance in PIK3CA, NF1 and TP53, suggesting the tumors were clonal. A total of three cycles of single-agent pembrolizumab, and radiation to the lung and brain administered between cycles 1 and 2, resulted in marked responses in lung, brain and pancreatic tumors. Despite the discontinuation of the pembrolizumab after three cycles due to severe immune-mediated toxicities, the patient has had no progression 11 months after stopping all active treatment. Results of a novel 27-gene immuno-oncology (IO) expression assay revealed strong IO scores for the lung and pancreatic tumors, indicating a favorable tumor immune-microenvironment and possibly explaining the significant response.
Pembrolizumab for the treatment of PD-L1 positive advanced or metastatic non-small cell lung cancer. [2020]The emergence of immune checkpoint inhibitors marked an important advancement in the development of cancer therapeutics. Pembrolizumab is a selective humanized IgG4 kappa monoclonal antibody that inhibits the programmed death-1 (PD-1) receptor, an integral component of immune checkpoint regulation in the tumor microenvironment. The drug is currently approved by the Food and Drug Administration for the treatment of advanced melanoma and metastatic squamous and nonsquamous non-small cell lung cancer (NSCLC). Several published studies demonstrate that single-agent pembrolizumab is safe and has efficacy in patients with NSCLC. Many ongoing protocols are investigating the role of pembrolizumab in combination with other agents in lung cancer and various other cancer types. We review the available data on pembrolizumab in NSCLC and examine the role of potential predictive biomarkers of response to therapy.
Clinicopathologic correlates of first-line pembrolizumab effectiveness in patients with advanced NSCLC and a PD-L1 expression of ≥ 50. [2020]Single-agent pembrolizumab represents the standard first-line option for metastatic non-small-cell lung cancer (NSCLC) patients with a PD-L1 (programmed death-ligand 1) expression of ≥ 50%.