MDNA11 + Pembrolizumab for Cancer
(ABILITY-1 Trial)
Recruiting in Palo Alto (17 mi)
+19 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 1 & 2
Recruiting
Sponsor: Medicenna Therapeutics, Inc.
Must not be taking: Corticosteroids, Immunosuppressants
Disqualifiers: Active CNS metastases, Autoimmune disease, Severe systemic disease, others
No Placebo Group
Breakthrough Therapy
Trial Summary
What is the purpose of this trial?This is a Phase 1/2, multi-center, open-label, dose-escalation and expansion study to evaluate safety and tolerability, PK, pharmacodynamic, and early signal of anti-tumor activity of MDNA11 alone or in combination with a checkpoint inhibitor in patients with advanced solid tumors.
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 have had any systemic anti-cancer therapy within 4 weeks before starting the trial, and certain other treatments like corticosteroids or investigational drugs may also need to be stopped. It's best to discuss your specific medications with the trial team.
What data supports the effectiveness of the drug MDNA11 + Pembrolizumab for cancer?
Pembrolizumab, a part of the treatment, has shown effectiveness in treating advanced melanoma and non-small-cell lung cancer (NSCLC), with studies indicating improved response rates and survival outcomes in these conditions. Additionally, PD-1 blockade, which is a mechanism of pembrolizumab, achieved responses in 70% of patients with desmoplastic melanoma.
12345What is known about the safety of MDNA11 and Pembrolizumab for cancer treatment?
Pembrolizumab, a type of immune therapy, is generally well tolerated but can cause side effects like fatigue, rash, and diarrhea. It may also lead to less common immune-related issues such as thyroid problems, lung inflammation, and liver inflammation. There is no specific safety data available for MDNA11 in the provided research.
26789What makes the drug MDNA11 + Pembrolizumab unique for cancer treatment?
MDNA11 is an IL-2 Superkine, which means it is a modified version of a protein that can boost the immune system's ability to fight cancer, and when combined with Pembrolizumab, an anti-PD-1 drug, it may enhance the immune response against cancer cells more effectively than using Pembrolizumab alone.
2451011Eligibility Criteria
Adults with advanced solid tumors that can't be surgically removed, who have measurable disease and a life expectancy of at least 12 weeks. They must function relatively well daily (ECOG 0-1), have good organ function, not be pregnant or breastfeeding, and agree to use effective birth control. Exclusions include recent other cancer treatments, active brain metastases, significant autoimmune diseases, certain infections like hepatitis B/C, or any condition that could affect safety or study results.Inclusion Criteria
Agree to use highly effective contraception methods. WOCBP must agree to use highly effective birth control
My cancer is advanced or has spread and confirmed by lab tests.
Must be able and willing to provide written informed consent prior to start of any study procedures and assessments and must be willing to comply with all study procedures
+6 more
Exclusion Criteria
I received my last cancer treatment within the required timeframe.
Currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to start of treatment. Concomitant participation in an observational study must be discussed on a case-by-case basis with the MM for approval
I have brain metastases but they are stable after treatment.
+12 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants receive MDNA11 alone or in combination with pembrolizumab, with tumor assessments every 8 weeks
24 months
Every 8 weeks for tumor assessment
Follow-up
Participants are monitored for safety and effectiveness after treatment
4 weeks
Participant Groups
The trial is testing MDNA11 alone or combined with Pembrolizumab in patients with various advanced cancers. It's an early-phase study assessing the drugs' safety profiles, how they move through and affect the body (pharmacokinetics/dynamics), and their preliminary effectiveness against tumors.
1Treatment groups
Experimental Treatment
Group I: MDNA11Experimental Treatment2 Interventions
MDNA11 is a long-acting "beta-only" recombinant interleukin-2 (rIL-2) albumin fusion
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Princess Margaret Cancer CenterToronto, Canada
Providence Saint John's Health CenterSanta Monica, CA
Emory - Winship Cancer InstituteAtlanta, GA
Gabrail Cancer Center ResearchCanton, OH
More Trial Locations
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Who Is Running the Clinical Trial?
Medicenna Therapeutics, Inc.Lead Sponsor
Merck Sharp & Dohme LLCIndustry Sponsor
References
Long-Term Overall Survival From KEYNOTE-021 Cohort G: Pemetrexed and Carboplatin With or Without Pembrolizumab as First-Line Therapy for Advanced Nonsquamous NSCLC. [2021]In cohort G of KEYNOTE-021 (NCT02039674), first-line pembrolizumab plus pemetrexed-carboplatin significantly improved the objective response rate and progression-free survival versus chemotherapy alone with manageable toxicity in advanced nonsquamous NSCLC. We report the long-term outcomes from this study.
Pembrolizumab for myelodysplastic syndromes after failure of hypomethylating agents in the phase 1b KEYNOTE-013 study. [2022]The phase 1b multicohort KEYNOTE-013 study assessed the safety and antitumor activity of pembrolizumab given at 10 mg/kg/day every 2 weeks for up to 2 years in hematologic malignancies, including myelodysplastic syndromes (MDS) refractory to a hypomethylating agent (HMA). Primary outcomes were safety and objective response rate per International Working Group 2006 criteria. By June 26, 2020, 28 patients were enrolled; median duration of follow-up was 5.6 months (range, 1-78), and 25 patients (89%) had died. Treatment-related adverse events occurred in 10 patients (36%), including 2 (7%) treatment-related discontinuations. No patient achieved complete or partial response. Five patients (19%) had bone marrow complete response, 12 (44%) stable disease, 10 (37%) progressive disease, 6 (22%) cytogenetic response, and 5 (19%) hematologic improvement. Median overall survival (OS) was 6.0 months (95% CI, 4-12); the overall 2-year OS rate was 17%. Pembrolizumab had manageable safety and clinical activity in patients with HMA-refractory MDS.This trial was registered at www.clinicaltrials.gov as #NCT01953692.
Patients with Desmoplastic Melanoma May Respond to PD-1 Blockade. [2019]PD-1 blockade achieved responses in 70% of patients with desmoplastic melanoma in a retrospective analysis.
Pembrolizumab versus Chemotherapy for PD-L1-Positive Non-Small-Cell Lung Cancer. [2022]Pembrolizumab is a humanized monoclonal antibody against programmed death 1 (PD-1) that has antitumor activity in advanced non-small-cell lung cancer (NSCLC), with increased activity in tumors that express programmed death ligand 1 (PD-L1).
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).
A Phase I/IIa Randomized Trial Evaluating the Safety and Efficacy of SNK01 Plus Pembrolizumab in Patients with Stage IV Non-Small Cell Lung Cancer. [2022]The aim of this study is to evaluate the safety and efficacy of ex vivo activated and expanded natural killer (NK) cell therapy (SNK01) plus pembrolizumab in a randomized phase I/IIa clinical trial.
Pembrolizumab-induced sarcoid granulomatous panniculitis and bullous pemphigoid in a single patient. [2021]Pembrolizumab is an immune checkpoint inhibitor with antitumor activity in other organ malignancies. We present this case -demonstrating multiple inflammatory adverse events associated with Pembrolizumab (in a single patient), in order to increase awareness and facilitate earlier identification of the wide-ranging cutaneous side effects associated with immunotherapy.
Pembrolizumab in the management of metastatic melanoma. [2020]Pembrolizumab is a humanized IgG4 anti-PD-1 antibody that plays a major role in the treatment of advanced melanoma. Through blockade of PD-1, it leads to an increase in effector T-cell activity in the tumor microenvironment. Clinical trial outcomes for pembrolizumab in addition to pharmacokinetics, pharmacodynamics and safety of the compound are discussed in this article. Phase I trials have demonstrated safety and efficacy of pembrolizumab in advanced, pretreated melanoma patients. When compared with chemotherapy in a Phase II trial of ipilimumab-refractory patients, those treated with pembrolizumab showed superior progression-free survival. In addition, in the pivotal Phase III trial pembrolizumab improved overall survival compared with ipilimumab in patients naive to immune checkpoint inhibition. Pembrolizumab is well tolerated and has a favorable safety profile. Common adverse events are fatigue, rash, itching and diarrhea. Less frequent immune-related adverse events include hypothyroidism, colitis, hepatitis and pneumonitis.
Multiple autoimmune side effects of immune checkpoint inhibitors in a patient with metastatic melanoma receiving pembrolizumab. [2021]Immune agents including anti-programmed death receptor-1 and anti-cytotoxic T-lymphocyte antigen-4 have been associated with numerous immune-related complications. Pembrolizumab, a programmed death-1 inhibitor, has been associated with a number of immune-related adverse events such as pneumonitis, colitis, hepatitis, hypophysitis, hyperthyroidism, hypothyroidism, nephritis, and type 1 diabetes.
Preclinical Pharmacokinetics and Biodistribution Studies of 89Zr-Labeled Pembrolizumab. [2020]Pembrolizumab is a humanized monoclonal antibody targeting programmed cell death protein 1 (PD-1) found on T and pro-B cells. Pembrolizumab prevents PD-1 ligation by both PD-L1 and PD-L2, preventing the immune dysregulation that otherwise occurs when T-cells encounter cells expressing these ligands. Clinically, PD-1 blockade elicits potent antitumor immune responses, and antibodies blocking PD-1 ligation, including pembrolizumab, have recently received Food and Drug Administration approval for the treatment of advanced melanoma, renal cell cancer, and non-small cell lung cancer.
Pembrolizumab joins the anti-PD-1 armamentarium in the treatment of melanoma. [2017]Pembrolizumab (MK-3475) is a monoclonal antibody that binds to the PD-1 receptor on T cells and prevents binding to its ligands PD-L1 and PD-L2. Blocking this receptor frees T cells from the inhibitory effects of PD-L1 and allows them to mediate antitumor effects against cancer cells. In a large Phase I study of 411 patients with melanoma, high durable response rates over a range of doses and schedules have been shown with very little toxicity. A Phase III study of pembrolizumab comparing two schedules of administration with the current standard treatment with the anti-CTLA-4 monoclonal antibody is in progress. Combinations with other checkpoint inhibitors as well as other anticancer agents are also being evaluated. Approval of pembrolizumab for the treatment of melanoma is expected.