ASP1012 + Pembrolizumab for Cancer
Recruiting in Palo Alto (17 mi)
+4 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 1
Recruiting
Sponsor: Astellas Pharma Global Development, Inc.
Must not be taking: Corticosteroids, Immunosuppressives, Antivirals, others
Disqualifiers: Autoimmune disorders, CNS metastases, HIV, others
No Placebo Group
Breakthrough Therapy
Trial Summary
What is the purpose of this trial?This trial tests ASP1012, a modified virus that targets and kills cancer cells, in adults with advanced or spreading tumors. The study aims to find a safe dose and check for side effects. ASP1012 helps the immune system recognize and fight cancer cells.
Will I have to stop taking my current medications?
The trial protocol does not specify if you must stop taking your current medications. However, it mentions that participants must comply with prohibited medication restrictions, so it's best to discuss your specific medications with the study team.
What data supports the effectiveness of the drug pembrolizumab in cancer treatment?
Research shows that pembrolizumab, a drug that helps the immune system fight cancer, improves survival in patients with advanced lung cancer and melanoma. It has been effective in patients with specific markers on their cancer cells, leading to longer life and better quality of life compared to traditional chemotherapy.
12345Is the combination of ASP1012 and Pembrolizumab safe for humans?
Pembrolizumab, also known as KEYTRUDA or MK-3475, has been studied for safety in various cancers. It generally has a favorable safety profile, but there are rare serious side effects, including infections, heart issues, and lung inflammation. The risk of fatal adverse events is similar to chemotherapy, and it varies depending on the type of cancer and whether it is combined with other treatments.
56789What makes the drug ASP1012 + Pembrolizumab unique for cancer treatment?
The combination of ASP1012 with Pembrolizumab is unique because it aims to enhance the immune system's ability to fight cancer by combining Pembrolizumab, a well-established immune checkpoint inhibitor, with ASP1012, which may have a novel mechanism or target. This combination could potentially improve outcomes in cancers that are less responsive to Pembrolizumab alone.
810111213Eligibility Criteria
Adults with advanced solid tumors that have grown or spread and who've tried all standard treatments can join. It's not for those with a specific skin cancer (acral lentiginous melanoma) or ovarian cancer patients in remission without measurable disease. Participants must have confirmed diagnoses, and some will need to show certain biomarkers.Inclusion Criteria
I had Stage II-IV colon cancer, treated with surgery and chemotherapy, and have no visible cancer but positive for ctDNA.
I have had melanoma treatment with specific immunotherapies or targeted therapies if my melanoma has a BRAF mutation.
I have stage II-IV ovarian cancer in remission with a CA-125 level over 70 U/mL after standard treatment.
+7 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Dose Escalation
Participants with locally advanced or metastatic tumors receive escalating doses of ASP1012 to determine suitable doses for further study parts.
Up to 28 days
Multiple visits (in-person)
Dose Expansion
Participants receive ASP1012 at doses determined from Dose Escalation phase, with or without pembrolizumab, depending on cancer type.
3 cycles of 21 days each
Clinic visits every 21 days, some virtual or by phone
Follow-up
Participants are monitored for safety and effectiveness after treatment, with clinic visits and phone follow-ups.
Up to 19 months
Clinic visits within 7 and 30 days post-treatment, phone follow-ups every 12 weeks
Participant Groups
ASP1012, an oncolytic virus designed to target and kill cancer cells while sparing healthy ones, is being tested alone or with pembrolizumab (an approved drug). The trial has three parts: dose finding, expanding the dose to more patients, and testing in specific cancers like stomach and colorectal.
8Treatment groups
Experimental Treatment
Group I: Part 3: ASP1012 Dose Expansion (previously treated gastric cancer)Experimental Treatment1 Intervention
Participants with previously treated gastric cancer will receive ASP1012 with dose level selected from dose escalation (Part 1) in a 21-day cycle.
Group II: Part 3: ASP1012 Dose Expansion (ovarian cancer)Experimental Treatment1 Intervention
Participants with ovarian cancer will receive ASP1012 with dose level selected from dose escalation (Part 1) in a 21-day cycle.
Group III: Part 3: ASP1012 Dose Expansion (other solid tumor type)Experimental Treatment1 Intervention
Participants with other solid tumor type will receive ASP1012 with dose level selected from dose escalation (Part 1) in a 21-day cycle.
Group IV: Part 3: ASP1012 Dose Expansion (colorectal cancer [CRC])Experimental Treatment1 Intervention
Participants with CRC will receive ASP1012 with dose level selected from dose escalation (Part 1) in a 21-day cycle.
Group V: Part 2: ASP1012 Dose Expansion (Monotherapy)Experimental Treatment1 Intervention
Participants with previously treated melanoma will receive ASP1012 with dose level(s) selected from dose escalation (Part 1) in a 21-day cycle.
Group VI: Part 2: ASP1012 + Pembrolizumab Dose Expansion (treatment-naïve melanoma)Experimental Treatment2 Interventions
Participants with treatment-naïve melanoma will receive ASP1012 in a 21-day cycle. Pembrolizumab will also be administered every three weeks in a 21-day cycle, for up to 3 doses.
Group VII: Part 2: ASP1012 + Pembrolizumab Dose Expansion (previously treated solid tumors)Experimental Treatment2 Interventions
Participants with previously treated solid tumors, will receive ASP1012 in a 21-day cycle. Pembrolizumab will also be administered every three weeks in a 21-day cycle, for up to 3 doses.
Group VIII: Part 1: ASP1012 Dose EscalationExperimental Treatment1 Intervention
Participants with previously treated solid tumor types will receive ASP1012 in a 21-day cycle.
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
University of Iowa HospitalsIowa City, IA
Emory Winship Cancer InstituteAtlanta, GA
Karmanos Cancer InstituteDetroit, MI
Hoag Memorial Hospital PresbyterianNewport Beach, CA
More Trial Locations
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Who Is Running the Clinical Trial?
Astellas Pharma Global Development, Inc.Lead Sponsor
References
[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.
Pembrolizumab versus chemotherapy for previously untreated, PD-L1-expressing, locally advanced or metastatic non-small-cell lung cancer (KEYNOTE-042): a randomised, open-label, controlled, phase 3 trial. [2022]First-line pembrolizumab monotherapy improves overall and progression-free survival in patients with untreated metastatic non-small-cell lung cancer with a programmed death ligand 1 (PD-L1) tumour proportion score (TPS) of 50% or greater. We investigated overall survival after treatment with pembrolizumab monotherapy in patients with a PD-L1 TPS of 1% or greater.
New developments in the management of advanced melanoma - role of pembrolizumab. [2020]Cancer immunotherapy is now recognized to be fundamental in modern oncology, because immune system recruitment may represent a powerful and innovative strategy in cancer therapy. Pembrolizumab, a highly selective humanized monoclonal antibody directly blocking the interaction between programmed cell death-1 expressed by tumor-associated T-cells and its ligand programmed cell death-L1 present on tumor and stromal cells, was recently approved by US Food and Drug Administration for the treatment of patients with unresectable or metastatic melanoma and disease progression upon ipilimumab and BRAF inhibitor. This review will focus on the clinical development and use of pembrolizumab in the clinical practice and in the management of advanced melanoma.
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.
Health-related quality-of-life results for pembrolizumab versus chemotherapy in advanced, PD-L1-positive NSCLC (KEYNOTE-024): a multicentre, international, randomised, open-label phase 3 trial. [2022]In the phase 3 KEYNOTE-024 trial, treatment with pembrolizumab conferred longer progression-free survival than did platinum-based therapy in patients with treatment-naive, advanced non-small-cell lung cancer (NSCLC) with a programmed cell death-ligand 1 (PD-L1) tumour proportion score of 50% or greater (PD-L1-positive). Here we report the prespecified exploratory endpoint of pembrolizumab versus chemotherapy on patient-reported outcomes (PROs).
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.
Five-year survival outcomes for patients with advanced melanoma treated with pembrolizumab in KEYNOTE-001. [2023]Pembrolizumab demonstrated robust antitumor activity and safety in the phase Ib KEYNOTE-001 study (NCT01295827) of advanced melanoma. Five-year outcomes in all patients and treatment-naive patients are reported herein. Patients whose disease progressed following initial response and who received a second course of pembrolizumab were also analyzed.
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.
Fatal Adverse Events Associated with Pembrolizumab in Cancer Patients: A Meta-Analysis. [2020]Background: Pembrolizumab as an immune checkpoint inhibitor (ICI) has emerged as an effective treatment for many cancers. It has unique immune-related adverse events (irAE) and little is known about its risk of fatal adverse events (FAEs). We conducted a meta-analysis of clinical trials to determine the incidence and risk of FAEs with pembrolizumab.Methods: A systematic search for phase I-III clinical trials of pembrolizumab was conducted using databases including PUBMED and abstracts presented at the American Society of Clinical Oncology (ASCO) conferences until October 2018. Eligible studies included prospective clinical trials of pembrolizumab with available data on FAE. Data on FAE was extracted from each study and pooled for calculations. Incidence, relative risk (RR) and 95% confidence intervals (CI) were calculated by employing fixed or random-effects models.Results: A total of 11 clinical trials with 3713 patients were included for analysis. The overall incidence of FAE with pembrolizumab was 1.2% (95% CI: 0.5-2.8%). The incidence of FAE significantly varied among different tumor types (p = .02), ranging from 0.2% in melanoma to 3.1% in breast cancer, and with its combination with chemotherapy (0.7%, 95% CI: 0.4-1.2% versus 7.0%, 95% CI: 4.9-10%; p<.01). Chemotherapy plus pembrolizumab 7.0% (95%CI: 4.9-10) as compared to pembrolizumab alone 0.7%, (95% CI: 0.4-1.2; p < .001). There was no significant difference in the risk of FAEs when pembrolizumab was compared with chemotherapy with RR = 1.24 (95% CI: 0.8-1.89; p = .31). The most common FAEs were due to infectious complication (26.5%), cardiac toxicity (14.7%) and pneumonitis (13.2%).Conclusions: The risk of FAEs with pembrolizumab may be similar to chemotherapy in cancer patients and may vary with tumor types and its combination with chemotherapy.
Clinical application effect of Pembrolizumab in the treatment of advanced cutaneous malignant melanoma. [2021]To investigate the clinical application value of Pembrolizumab (PEM) in the treatment of advanced cutaneous malignant melanoma (ACMM).
Evaluation of efficacy and safety of different pembrolizumab dose/schedules in treatment of non-small-cell lung cancer and melanoma: a systematic review. [2018]Pembrolizumab is a fully humanized anti-PD-1 agent currently approved for the treatment of advanced melanoma and pretreated non-small-cell lung cancer (NSCLC).
Clinical performance of endobronchial ultrasound-guided transbronchial needle aspiration for assessing programmed death ligand-1 expression in nonsmall cell lung cancer. [2018]Pembrolizumab was recently approved as a first line agent for metastatic NSCLC in patients with high programmed death-ligand 1 (PD-L1) expression.
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 .