MEM-288 + Nivolumab for Non-Small Cell Lung Cancer
Recruiting in Palo Alto (17 mi)
+1 other location
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 1
Recruiting
Sponsor: Memgen, Inc.
Must not be taking: Anticancer agents, Immunosuppressants
Disqualifiers: Pregnancy, Uncontrolled heart disease, Active infections, others
No Placebo Group
Breakthrough Therapy
Trial Summary
What is the purpose of this trial?
This phase I trial is designed in two parts. First as an open-label, dose escalation trial of MEM-288 monotherapy in which investigators aim to find the maximum tolerated dose (MTD) and recommended phase II dose (RP2D). Subjects with selected solid tumors including non-small cell lung cancer (NSCLC) who have a tumor lesion which is accessible for injection will undergo intratumoral injection of MEM-288. Following completion of the monotherapy study portion of the study, an expansion arm is designed to test MEM-288 with concurrent anti-PD-1 (nivolumab) therapy for patients with first relapsed or refractory advanced/metastatic NSCLC following front-line anti-PD-1/PD-L1 with or without concurrent chemotherapy. The study rationale is that the oncolytic effect of MEM-288 combined with the presence of CD40L and type 1 interferon (IFN) in injected tumors will provide a strong signal for dendritic cell (DC)-mediated T cell activation leading to generation of systemic anti-tumor T cell responses with broad specificity akin to what is observed in the abscopal effect. Further study rationale is the anti-tumor effect of MEM-288 will be enhanced by nivolumab by reversing T cell exhaustion.
Will I have to stop taking my current medications?
The trial information does not specify if you need to stop taking your current medications. However, you cannot use other anticancer agents while participating in the trial.
What data supports the effectiveness of the treatment MEM-288 + Nivolumab for Non-Small Cell Lung Cancer?
Research shows that MEM-288, an oncolytic virus, can activate the immune system to fight cancer by increasing T-cell responses and reducing tumor size in non-small cell lung cancer patients. Additionally, combining MEM-288 with checkpoint inhibitors like Nivolumab has shown promise in controlling distant tumors and lung metastases.12345
Is the combination of MEM-288 and Nivolumab safe for humans?
What makes the MEM-288 + Nivolumab treatment unique for non-small cell lung cancer?
MEM-288 is an oncolytic virus (a virus that infects and kills cancer cells) engineered to express interferon beta and CD40 ligand, which can enhance the immune response against cancer. This makes it different from standard treatments like nivolumab alone, which is an immune checkpoint inhibitor that helps the immune system recognize and attack cancer cells.89101112
Eligibility Criteria
Adults over 18 with certain advanced cancers (like NSCLC, melanoma, and pancreatic cancer) who've already tried standard treatments including chemotherapy. They must have a tumor that can be injected and not be pregnant or breastfeeding. People with serious medical issues, active infections, or recent major surgery aren't eligible.Inclusion Criteria
Measurable disease, as defined per RECIST version 1.1
My pancreatic cancer has worsened after chemotherapy that included gemcitabine or a 5-FU-based treatment.
I have melanoma and have been treated with BRAF inhibitors and anti-PD-1/PD-L1 inhibitors.
See 16 more
Exclusion Criteria
Concurrent use of other anticancer approved or investigational agents
I have an autoimmune disease but it's not vitiligo, Grave's, or psoriasis that doesn't need systemic treatment.
I have no ongoing moderate side effects from immunotherapy, except for manageable hormone issues.
See 13 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Monotherapy Treatment
Dose escalation trial of MEM-288 monotherapy to determine the maximum tolerated dose and recommended phase II dose
4.5 months
Intratumoral injection once every 3 weeks (planned 2 doses, maximum 6 doses)
Combination Treatment
Expansion arm testing MEM-288 with concurrent anti-PD-1 (nivolumab) therapy for patients with advanced/metastatic NSCLC
Up to 39 weeks
Intratumoral injection and intravenous infusion once every 3 weeks
Follow-up
Participants are monitored for safety and effectiveness after treatment
Up to 39 weeks
Treatment Details
Interventions
- MEM-288 (Virus Therapy)
Trial OverviewThe trial is testing MEM-288, an oncolytic virus given by injection directly into the tumor. Initially alone to find the safest dose, then combined with Nivolumab for those whose lung cancer worsened after standard treatment. The goal is to boost the body's immune response against cancer.
Participant Groups
2Treatment groups
Experimental Treatment
Group I: MEM-288 Intratumoral InjectionExperimental Treatment1 Intervention
Part 1 MEM-288 monotherapy: Patients with accessible, subcutaneous, or superficial lymph node lesion ≥ 1 cm3 that is palpable will receive intratumoral injection of MEM-288 once every 3 week (planned 2 doses, maximum 6 doses) at one of three dose cohort levels.
* Dose cohort level 1 (1 x 10\^10 viral particles)
* Dose cohort level 2 (3.3 x 10\^10 viral particles)
* Dose cohort level 3 (1 x 10\^11 viral particles)
Group II: Dose combination of MEM-288 Intratumoral Injection plus anti-PD1 (Nivolumab) Intravenous InfusionExperimental Treatment2 Interventions
Part 2 MEM-288 plus nivolumab combination: Patients with accessible, subcutaneous, or superficial lymph node lesion ≥ 1 cm3 that is palpable will receive intratumoral injection of MEM-288 maximum total dose of 1x10\^11 viral particles once every 3 week (planned 2 doses, maximum 6 doses). MEM-288 may be injected in multiple lesions until the maximum injection dose (1x10\^11 viral particles) is reached (minimum dose per lesion of 1x10\^10 viral particles). Nivolumab 360 mg IV every 3 weeks.
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Moffitt Cancer CenterTampa, FL
Duke Cancer InstituteDurham, NC
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Who Is Running the Clinical Trial?
Memgen, Inc.Lead Sponsor
Duke Cancer InstituteCollaborator
H. Lee Moffitt Cancer Center and Research InstituteCollaborator
References
Combination IFNβ and Membrane-Stable CD40L Maximize Tumor Dendritic Cell Activation and Lymph Node Trafficking to Elicit Systemic T-cell Immunity. [2023]Oncolytic virus therapies induce the direct killing of tumor cells and activation of conventional dendritic cells (cDC); however, cDC activation has not been optimized with current therapies. We evaluated the adenoviral delivery of engineered membrane-stable CD40L (MEM40) and IFNβ to locally activate cDCs in mouse tumor models. Combined tumor MEM40 and IFNβ expression induced the highest cDC activation coupled with increased lymph node migration, increased systemic antitumor CD8+ T-cell responses, and regression of established tumors in a cDC1-dependent manner. MEM40 + IFNβ combined with checkpoint inhibitors led to effective control of distant tumors and lung metastases. An oncolytic adenovirus (MEM-288) expressing MEM40 + IFNβ in phase I clinical testing induced cancer cell loss concomitant with enhanced T-cell infiltration and increased systemic presence of tumor T-cell clonotypes in non-small cell lung cancer (NSCLC) patients. This approach to simultaneously target two major DC-activating pathways has the potential to significantly affect the solid tumor immunotherapy landscape.
Characterization of a novel OX40 ligand and CD40 ligand-expressing oncolytic adenovirus used in the PeptiCRAd cancer vaccine platform. [2021]Oncolytic viruses (OVs) have been shown to induce anti-cancer immunity and enhance cancer immunotherapies, such as immune checkpoint inhibitor therapies. OV therapies can be further improved by arming OVs with immunostimulatory molecules, including various cytokines or chemokines. Here, we have developed a novel adenovirus encoding two immunostimulatory molecules: cluster of differentiation 40 ligand (CD40L) and tumor necrosis factor receptor superfamily member 4 ligand (OX40L). This novel virus, designated VALO-D102, is designed to activate both innate and adaptive immune responses against tumors. CD40L affects the innate side by licensing antigen-presenting cells to drive CD8+ T cell responses, and OX40L increases clonal expansion and survival of CD8+ T cells and formation of a larger pool of memory T cells. VALO-D102 and its murine surrogate VALO-mD901, expressing murine OX40L and CD40L, were used in our previously developed PeptiCRAd cancer vaccine platform. Intratumoral administration of PeptiCRAd significantly increased tumor-specific T cell responses, reduced tumor growth, and induced systemic anti-cancer immunity in two mouse models of melanoma. In addition, PeptiCRAd therapy, in combination with anti-PD-1 immune checkpoint inhibitor therapy, significantly improved tumor growth control as compared to either monotherapy alone.
Programmed Death 1 Blockade With Nivolumab in Patients With Recurrent Malignant Pleural Mesothelioma. [2020]Malignant pleural mesothelioma (MPM) has limited treatment options and a poor outcome. Programmed death 1/programmed death ligand 1 (PD-L1) checkpoint inhibitors have proven efficacious in several cancer types. Nivolumab is a fully humanized monoclonal antibody against programmed death 1 with a favorable toxicity profile. In MPM, the immune system is considered to play an important role. We therefore tested nivolumab in recurrent MPM.
Oncolytic measles virus encoding interleukin-12 mediates potent antitumor effects through T cell activation. [2021]Combination of oncolytic virotherapy with immunomodulators is emerging as a promising therapeutic strategy for numerous tumor entities. In this study, we developed measles Schwarz vaccine strain vectors encoding immunomodulators to support different phases in the establishment of antitumor immune responses. Therapeutic efficacy of the novel vectors was evaluated in the immunocompetent MC38cea tumor model. We identified vectors encoding an IL-12 fusion protein (MeVac FmIL-12) and an antibody against PD-L1 (MeVac anti-PD-L1), respectively, as the most effective. Treatment of established tumors with MeVac FmIL-12 achieved 90% complete remissions. Profiling of the tumor immune microenvironment revealed activation of a type 1 T helper cell-directed response, with MeVac FmIL-12 ensuring potent early natural killer and effector T cell activation as well as upregulation of the effector cytokines IFN-γ and TNF-α. CD8+ T cells were found to be essential for the therapeutic efficacy of MeVac FmIL-12. Results of this study present MeVac FmIL-12 as a novel approach for targeted IL-12 delivery and elucidate mechanisms of successful immunovirotherapy.
Clinical Efficacy and Safety of Nivolumab in Japanese Patients With Malignant Pleural Mesothelioma: 3-Year Results of the MERIT Study. [2022]We examined the long-term efficacy and safety of nivolumab, a human monoclonal antibody that inhibits interactions between the programmed cell death protein-1 receptor and its ligands (programmed death-ligand 1 and programmed death-ligand 2), in Japanese patients with malignant pleural mesothelioma (MPM).
Clinical Efficacy and Safety of Nivolumab: Results of a Multicenter, Open-label, Single-arm, Japanese Phase II study in Malignant Pleural Mesothelioma (MERIT). [2019]Malignant pleural mesothelioma (MPM) is a rare and aggressive malignancy with poor prognosis. Patients with MPM who do not respond to standard first-line chemotherapy have limited treatment options. We evaluated the efficacy and safety of nivolumab, an immune checkpoint inhibitor, for the treatment of advanced or metastatic MPM.
Correlation between immune-related adverse events and therapeutic effects of nivolumab in patients with malignant pleural mesothelioma. [2022]Nivolumab is used for the treatment of malignant pleural mesothelioma (MPM). However, immune-related adverse events (irAEs) occur in patients treated with nivolumab. Several studies have reported the correlation between irAEs and therapeutic effects of immune checkpoint inhibitor, but none have reported the correlation in MPM. Here we report a retrospective study which shows the correlation between irAEs and therapeutic effects of nivolumab in patients with MPM.
Change in the lymphocyte-to-monocyte ratio is an early surrogate marker of the efficacy of nivolumab monotherapy in advanced non-small-cell lung cancer. [2022]Nivolumab, an anti-programmed cell death protein 1 (PD-1) monoclonal antibody, has been shown to yield a durable response and significant prolongation of the survival in some patients with non-small-cell lung cancer (NSCLC). However, identification of patients who are likely to respond to nivolumab remains difficult at present.
Activity and safety of nivolumab, an anti-PD-1 immune checkpoint inhibitor, for patients with advanced, refractory squamous non-small-cell lung cancer (CheckMate 063): a phase 2, single-arm trial. [2022]Patients with squamous non-small-cell lung cancer that is refractory to multiple treatments have poor outcomes. We assessed the activity of nivolumab, a fully human IgG4 PD-1 immune checkpoint inhibitor antibody, for patients with advanced, refractory, squamous non-small-cell lung cancer.
Population Pharmacokinetics of Nivolumab in Japanese Patients with Nonsmall Cell Lung Cancer. [2023]Nivolumab is an antiprogrammed death-1 (PD-1) antibody used for immuno-oncological therapy of various cancers, including nonsmall cell lung cancer (NSCLC). This study aimed to characterize the real-world population pharmacokinetics (PK) of nivolumab in patients with NSCLC.
Italian Nivolumab Expanded Access Program in Nonsquamous Non-Small Cell Lung Cancer Patients: Results in Never-Smokers and EGFR-Mutant Patients. [2019]Nivolumab is the first checkpoint inhibitor approved for the treatment of nonsquamous NSCLC. We report results from the nivolumab Italian expanded access program focusing on never-smokers and patients with EGFR-mutant nonsqamous NSCLC.
Real-world benefit of nivolumab in a Canadian non-small-cell lung cancer cohort. [2020]Nivolumab was the first immuno-oncology agent available for the treatment of lung cancer in Canada. In the present study, we evaluated the real-world benefit of nivolumab in Canadian patients with lung cancer.