VET3-TGI + Pembrolizumab for Solid Tumors
(STEALTH-001 Trial)
Recruiting in Palo Alto (17 mi)
+5 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 1
Recruiting
Sponsor: KaliVir Immunotherapeutics
Must not be taking: Anti-coagulants, Immunosuppressants
Disqualifiers: CNS metastases, Myocarditis, HIV/AIDS, others
No Placebo Group
Breakthrough Therapy
Trial Summary
What is the purpose of this trial?VET3-TGI is an oncolytic immunotherapy designed to treat advanced cancers. VET3-TGI has not been given to human patients yet, and the current study is designed to find a safe and effective dose of VET3-TGI when administered by direct injection into tumor(s) (called an intratumoral injection) or when given intravenously (into the vein) both alone and in combination with pembrolizumab in patients with solid tumors (STEALTH-001).
Will I have to stop taking my current medications?
The trial requires a washout period (time without taking certain medications) for prior systemic therapies, depending on the therapy. If you are on anti-platelet or anti-coagulant medications, you may need to stop them if they cannot be safely suspended for the trial procedures.
What data supports the effectiveness of the drug Pembrolizumab for solid tumors?
Pembrolizumab has shown effectiveness in treating various types of cancers, including non-small cell lung cancer and tumors with specific genetic features like microsatellite instability high (MSI-H) or mismatch repair deficiency (dMMR). It works by helping the immune system attack cancer cells, and has been approved for use in several cancer types due to its ability to produce durable responses.
12345Is the combination of VET3-TGI and Pembrolizumab safe for humans?
Pembrolizumab, also known as KEYTRUDA or MK-3475, has been studied in various cancers and generally shows an acceptable safety profile. Common side effects include diarrhea, fatigue, and nausea, but no major safety concerns have been identified that would prevent its use.
678910What makes the drug VET3-TGI + Pembrolizumab unique for treating solid tumors?
The combination of VET3-TGI with pembrolizumab is unique because it potentially enhances the immune response against solid tumors by combining pembrolizumab, an immune checkpoint inhibitor, with VET3-TGI, which may have a novel mechanism of action not yet detailed in existing research. This combination could offer a new approach for patients with solid tumors, especially those who have limited treatment options.
4791112Eligibility Criteria
This trial is for adults with advanced solid tumors who have not responded to, cannot tolerate, or refused standard treatments like targeted therapy, immunotherapy, and chemotherapy. Participants must have at least one tumor that can be safely injected or biopsied and should be in good physical condition (ECOG status 0-1). They need to show proper organ function and agree to follow the study procedures.Inclusion Criteria
My organs are functioning well.
I am willing to follow all study rules and after-treatment care instructions.
Measurable disease as per RECIST 1.1 criteria
+4 more
Exclusion Criteria
I have completed the required waiting period after my last systemic therapy.
I do not have HIV/AIDS, or active hepatitis B or C.
I need blood-thinning medication that can't be stopped for certain medical procedures.
+3 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Dose Escalation
Dose escalation of VET3-TGI alone administered by direct injection into tumor(s) or by intravenous infusion to determine the highest tolerated dose
4 weeks
Treatment
Participants receive VET3-TGI alone or in combination with pembrolizumab at the highest tolerated dose, with booster injections or infusions permitted for up to 2 years
Up to 2 years
Follow-up
Participants are monitored for safety and effectiveness after treatment
108 months
Participant Groups
The study tests VET3-TGI, a new oncolytic immunotherapy given directly into the tumor or through the vein. It's being tested alone and alongside pembrolizumab to find safe doses for patients with various types of solid tumors including breast, bladder, cervical cancers among others.
4Treatment groups
Experimental Treatment
Group I: Group D: VET3-TGI intravenous in combination with pembrolizumabExperimental Treatment2 Interventions
VET3-TGI will be given in combination with pembrolizumab at the highest tolerated dose from Group C. Pembrolizumab will be administered via intravenous (IV) infusion for up to 2 years.
Group II: Group C: VET3-TGI alone intravenousExperimental Treatment1 Intervention
Dose escalation of VET3-TGI alone administered by IV infusion x 6. Booster infusions of VET3-TGI are permitted for up to 2 years.
Group III: Group B: VET3-TGI intratumoral in combination with pembrolizumabExperimental Treatment2 Interventions
VET3-TGI will be given in combination with pembrolizumab at the highest tolerated dose from Group A. Pembrolizumab will be administered via intravenous (IV) infusion for up to 2 years.
Group IV: Group A: VET3-TGI alone intratumoralExperimental Treatment1 Intervention
Dose escalation of VET3-TGI alone administered by direct injection into tumor(s) x 4. Booster injections of VET3-TGI are permitted for up to 2 years.
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Mary Crowley Cancer ResearchDallas, TX
University of Texas MD Anderson Cancer CenterHouston, TX
USC/Norris Comprehensive Cancer CenterLos Angeles, CA
Community Health NetworkIndianapolis, IN
More Trial Locations
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Who Is Running the Clinical Trial?
KaliVir ImmunotherapeuticsLead Sponsor
References
Pembrolizumab in microsatellite instability high or mismatch repair deficient cancers: updated analysis from the phase II KEYNOTE-158 study. [2022]Pembrolizumab demonstrated durable antitumor activity in 233 patients with previously treated advanced microsatellite instability high (MSI-H) or mismatch repair deficient (dMMR) advanced solid tumors in the phase II multicohort KEYNOTE-158 (NCT02628067) study. Herein, we report safety and efficacy outcomes with longer follow-up for more patients with previously treated advanced MSI-H/dMMR noncolorectal cancers who were included in cohort K of the KEYNOTE-158 (NCT02628067) study.
Outcomes to first-line pembrolizumab in patients with PD-L1-high (≥50%) non-small cell lung cancer and a poor performance status. [2021]Patients with non-small cell lung cancer (NSCLC) and a poor Eastern Cooperative Oncology Group Performance Status (ECOG PS) have been excluded from phase III immunotherapy clinical trials. We sought to evaluate clinical outcomes to first-line pembrolizumab in patients with advanced NSCLC, a PD-L1 Tumor Proportion Score (TPS) of ≥50%, and an ECOG PS of 2.
Clinical utility of pembrolizumab in the management of advanced solid tumors: an evidence-based review on the emerging new data. [2023]Pembrolizumab is a full-length human immunoglobulin G4 (IgG4) monoclonal antibody directed against the immune checkpoint PD-1 to remove its binding with PD-L1 and thus to restore an anti-tumor immune response of T cells. Pembrolizumab is one of the most advanced immune checkpoint inhibitors for cancer care. Apart from rare and serious adverse effects, its favorable tolerance profile enables to treat fragile patients who have often no other choice than best supportive care. The effective retained dose of pembrolizumab is a venous administration of 200 mg every 3 weeks until disease progression, intolerance or up to 24 months. Pembrolizumab has already proven its efficacy and thus obtained marketing authorization in so-called hot or hypermutated tumors or tumors expressing PD-L1 such as melanomas, non-small cell lung cancers, urothelial carcinomas, cervical cancer, etc. Pembrolizumab is also authorized in the United States in the treatment of mismatch repair-deficient tumors or with microsatellite instability. The current challenge is to expand its use in tumor types that are supposed to be less immunogenic, for example, by attempting to warm up the tumor microenvironment, or by combining pembrolizumab with other molecules. An acceptable toxicity profile of such combinations remains to explore. We review here the current indications of this drug, the main prognostic and predictive factors of its efficacy as well as the potential forthcoming indications.
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.
Pembrolizumab in the treatment of metastatic non-small cell lung cancer: a review of current evidence. [2023]Immune checkpoint inhibitors (ICPIs) are considered one of the most important breakthroughs in cancer treatment of the past decade; notably, different studies of programmed cell death protein 1 (PD-1) and programmed death-ligand 1 (PD-L1) inhibitors have reported impressive clinical activity and durable responses in patients with advanced non-small cell lung cancer (NSCLC). These findings have led to the changing of the current therapeutic algorithm of advanced NSCLC, adding a new standard first-line treatment option for patients with PD-L1-positive tumors. Pembrolizumab, a highly selective anti-PD-1 humanized monoclonal antibody, was approved by the United States Food and Drug Administration (US FDA) in October 2016 for previously untreated metastatic NSCLC patients whose tumors have high PD-L1 expression, tumor proportion score (TPS) ⩾ 50%, as well as for metastatic NSCLC patients whose tumors express PD-L1 with TPS ⩾ 1% progressing on or after platinum-based chemotherapy. However, many issues remain outstanding, mainly regarding the identification of an optimal biomarker which can help selecting patients more likely to respond to ICPIs. In this review, we discuss the clinical results obtained so far with the anti-PD-1 pembrolizumab in advanced NSCLC, commenting on the role of PD-L1 as a predictive factor and providing an update of the future perspectives.
FDA Approval Summary: Pembrolizumab for the First-line Treatment of Patients with MSI-H/dMMR Advanced Unresectable or Metastatic Colorectal Carcinoma. [2022]The FDA approved pembrolizumab on June 29, 2020, for the treatment of patients with unresectable or metastatic microsatellite instability-high (MSI-H) colorectal cancer with no prior systemic treatment for advanced disease. The approval was based on data from Study Keynote-177, which randomly allocated patients to receive either pembrolizumab or standard of care (SOC) with chemotherapy. Overall survival (OS) and independently assessed progression-free survival (PFS) were the primary endpoints. At the time of the final PFS analysis and second prespecified interim OS analysis, the estimated median PFS was 16.5 months (95% CI: 5.4-32.4) versus 8.2 months (95% CI: 6.1-10.2) in the pembrolizumab and SOC arms, respectively [HR: 0.60 (95% CI: 0.45-0.80); two-sided P = 0.0004]. FDA assessed unblinded OS data during the review of the application and identified no safety concerns that would preclude approval of this supplement. Adverse reactions occurring in >30% of patients receiving pembrolizumab were diarrhea, fatigue/asthenia, and nausea. Adverse reactions occurring in >30% of patients receiving SOC were diarrhea, nausea, fatigue/asthenia, neutropenia, decreased appetite, peripheral neuropathy (high-level term), vomiting, abdominal pain, constipation, and stomatitis. Duration of treatment in the pembrolizumab arm was almost double (median 11.1 months, range 0-30.6 months) than the duration of treatment in patients receiving SOC (median, 5.7 months). Approval of pembrolizumab is likely to change the treatment paradigm for first-line treatment with MSI-H advanced colorectal cancer given the study results and different safety profile.
Efficacy and Safety of Pembrolizumab in Previously Treated Advanced Neuroendocrine Tumors: Results From the Phase II KEYNOTE-158 Study. [2021]KEYNOTE-158 (ClinicalTrials.gov identifier: NCT02628067) investigated the efficacy and safety of pembrolizumab across multiple cancers. We present results from patients with previously treated advanced well-differentiated neuroendocrine tumors (NET).
Pembrolizumab. [2022]The development of the cytotoxic T-lymphocyte-associated protein 4 inhibitor ipilimumab and its approval in 2011 for the treatment of metastatic melanoma has heralded a new era in immuno-oncology. Subsequently, novel agents against the programmed death receptor 1 (PD-1)/programmed death receptor ligand 1 (PD-L1) axis have shown significant activity in melanoma and a variety of other tumor types. Pembrolizumab was the first anti-PD-1 antibody to be approved by the US Food and Drug Administration for the treatment of patients with unresectable or metastatic melanoma with disease progression following ipilimumab, and if BRAF (V600) mutation positive, a BRAF inhibitor. Pembrolizumab has also received breakthrough status for the treatment of EGFR mutation-negative, ALK rearrangement-negative non-small cell lung cancer (NSCLC) that has progressed on or following platinum-based chemotherapy. There remain a number of pivotal trials in progress to further evaluate the optimal use of pembrolizumab alone and in combination for melanoma, NSCLC, and other tumor types. In this article, we review the efficacy and toxicity profile of pembrolizumab and evaluate its future development.
Pembrolizumab for advanced non-small cell lung cancer (NSCLC): Impact of autoimmune comorbidity and outcomes following treatment completion. [2023]Pembrolizumab, an immune-checkpoint inhibitor, is approved for first-line treatment of metastatic NSCLC in patients with tumours expressing programmed death-ligand 1 (PD-L1) with tumour proportion score (TPS) of ≥50%. We aimed to clarify some uncertainties regarding use of immunotherapy in patients with previous autoimmune (AI) disorders and assess real-world outcomes following treatment completion.
Pembrolizumab for Early Triple-Negative Breast Cancer. [2022]Previous trials showed promising antitumor activity and an acceptable safety profile associated with pembrolizumab in patients with early triple-negative breast cancer. Whether the addition of pembrolizumab to neoadjuvant chemotherapy would significantly increase the percentage of patients with early triple-negative breast cancer who have a pathological complete response (defined as no invasive cancer in the breast and negative nodes) at definitive surgery is unclear.
Impacts of pembrolizumab therapy on immune phenotype in patients with high-grade neuroendocrine neoplasms. [2022]High grade neuroendocrine neoplasms (G3 NENs) are rare aggressive tumors with limited treatment options. Twenty-one previously treated patients with metastatic extra-pulmonary G3 NENs were treated with pembrolizumab. Baseline tumor samples were assessed for PD-L1 and tumor infiltrating lymphocytes (TIL). Peripheral blood samples drawn pre-treatment, prior to cycle three, and at disease progression were analyzed by flow cytometry. One patient achieved partial response, two had stable disease, and 18 exhibited progressive disease. The partially responding patient did not progress after 392 days, and the median progression-free survival (PFS) was 59 days. Longer PFS correlated independently with higher pre-treatment peripheral blood T-cell counts and lower pre-treatment activation state (CD69 expression) of naïve T cells and NK cells. Peripheral T-cell viability was reduced in patients with greater TILs. Post-treatment, T cells had reduced numbers of CD4+ cells, reduced PD-1 expression, increased activation of effector (CD62L-) cells, and increased expression of TIGIT. Baseline TIGIT expression on peripheral T cells also correlated positively with Ki67 in tumor. Patients with higher baseline T-cell expression of TIM-3 had shorter PFS. Despite limited activity of pembrolizumab, this study highlights the immune phenotype in this rare tumor type before and after treatment. High baseline peripheral T-cell count and reduced activation of T and NK cell subsets were associated with improved outcomes. Furthermore, increased post-treatment TIGIT and elevated baseline TIM-3 expression suggest that these may limit the efficacy of pembrolizumab, providing a rationale for combination immunotherapy (PD-1 with TIGIT and/or TIM-3 antibodies) to treat extra-pulmonary G3 NENs.
Biomarker-directed, pembrolizumab-based combination therapy in non-small cell lung cancer: phase 2 KEYNOTE-495/KeyImPaCT trial interim results. [2023]Although pembrolizumab confers clinical benefit in non-small cell lung cancer (NSCLC), only a subset of patients will respond due to a heterogenous tumor microenvironment. KEYNOTE-495/KeyImPaCT is an ongoing biomarker-directed, adaptively randomized phase 2 study investigating first-line pembrolizumab (200 mg every 3 weeks) + lenvatinib (20 mg daily), anti-CTLA-4 quavonlimab (25 mg every 6 weeks) or anti-LAG-3 favezelimab (200 mg or 800 mg every 3 weeks) in advanced NSCLC. Patients were categorized by T-cell-inflamed gene expression profile (TcellinfGEP) and tumor mutational burden (TMB) status and randomly assigned 1:1:1 to receive pembrolizumab + lenvatinib, pembrolizumab + quavonlimab or pembrolizumab + favezelimab. The primary outcome was investigator-assessed objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors version 1.1 using pre-specified efficacy thresholds for each biomarker-defined subgroup (>5% (TcellinfGEPlowTMBnon-high (group I)), >20% (TcellinfGEPlowTMBhigh (group II) and TcellinfGEPnon-lowTMBnon-high (group III)) and >45% (TcellinfGEPnon-lowTMBhigh (group IV))). Secondary outcomes were progression-free survival, overall survival and safety. At data cutoff, ORR ranges were 0-12.0% in group I, 27.3-33.3% in group II, 13.6-40.9% in group III and 50.0-60.0% in group IV. ORR with pembrolizumab + lenvatinib in group III met the pre-specified efficacy threshold. The safety profile of each treatment arm was consistent with the known safety profile of each combination. These data demonstrate the feasibility of prospective TcellinfGEP and TMB assessment to study the clinical activity of first-line pembrolizumab-based combination therapies in advanced NSCLC. ClinicalTrials.gov registration: NCT03516981 .