MEM-288 + Nivolumab for Non-Small Cell Lung Cancer

Recruiting at 1 trial location

Overseen By Gregory B. Brown, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Memgen, Inc.

Must not be taking: Anticancer agents, Immunosuppressants

Disqualifiers: Pregnancy, Uncontrolled heart disease, Active infections, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 6

40 Participants Needed

Trial Summary

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. ^{1 2 3 4 5}

Is the combination of MEM-288 and Nivolumab safe for humans?

Nivolumab, used in various cancer treatments, has a favorable safety profile, but it can cause immune-related side effects. There is no specific safety data available for MEM-288 or its other names in humans. ^{3 4 5 6 7}

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. ^{8 9 10 11 12}

What is the purpose of this trial?

This is a multipart, open-label, multi-center dose escalation, dose expansion phase I clinical trial designed to evaluate the safety, tolerability, maximum tolerated dose (MTD), recommended phase 2 dose (RP2D), and preliminary efficacy of MEM-288 in patients with advanced solid tumors. Eligible subjects must have a tumor lesion(s) which is accessible for injection. The dose escalation phase (Part 1A - advanced solid tumors) has completed and is closed to enrollment. This phase evaluated multiple doses of MEM-288 dosed via intratumoral injection once every 3 weeks to assess safety, tolerability, preliminary efficacy, and to determine the MTD. The dose expansion phase has multiple parts for advanced NSCLC. Part 1B has completed after evaluation of MEM-288 dosed via intratumoral injection in combination with standard of care nivolumab dosed via intravenous injection. In a separate dose expansion arm (Part 1C) that is open for enrollment, patients with advanced NSCLC will be randomized to receive either an initial priming dose of MEM-288 injected into an accessible lesion (s) alone (Day 1) followed by MEM-288 in combination with standard of care docetaxel every 3 weeks up to 6 doses or MEM-288 injected into an accessible lesion(s) in combination with standard of care docetaxel therapy Day 1 and every 3 weeks up to 6 doses. The study rationale is that the oncolytic effect of MEM-288 combined with the presence of CD40L and type 1 IFN in injected tumors will provide a strong signal for 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.

Research Team

Andreas Saltos, MD

Principal Investigator

H. Lee Moffitt Cancer Center and Research Institute

Neal Ready, MD, PhD

Principal Investigator

Duke Cancer Institute

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.

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.

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

Trial Overview The 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

Group I: MEM-288 Intratumoral Injection plus anti-PD1 (Nivolumab) Intravenous Infusion (Complete) Experimental Treatment 2 Interventions

Part 1B 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.

Group II: MEM-288 Intratumoral Injection plus Docetaxel Intravenous Infusion (Open) Experimental Treatment 2 Interventions

Part 1C MEM-288 plus docetaxel combination: Patients with advanced NSCLC will be randomized 1:1 to receive either an initial priming dose of MEM-288 (1x10\^11 viral particles) injected into an accessible lesion(s) alone (Day 1) followed by MEM-288 in combination with standard of care docetaxel every 3 weeks, with up to 6 doses MEM-288, or MEM-288 injected into an accessible lesion(s) in combination with standard of care docetaxel therapy Day 1 and every 3 weeks up to 6 doses of MEM-288.

Group III: MEM-288 Intratumoral Injection (Complete) Experimental Treatment 1 Intervention

Part 1A 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)

Who Is Running the Clinical Trial?

Memgen, Inc.

Lead Sponsor

Trials

1

Recruited

60+

Duke Cancer Institute

Collaborator

Trials

17

Recruited

3,000+

H. Lee Moffitt Cancer Center and Research Institute

Collaborator

Trials

576

Recruited

145,000+

Findings from Research

The combination of engineered CD40L (MEM40) and IFNβ delivered via an oncolytic adenovirus significantly enhances the activation of conventional dendritic cells (cDCs), leading to improved immune responses and tumor regression in mouse models.

In a phase I clinical trial, the oncolytic adenovirus (MEM-288) expressing MEM40 and IFNβ showed promising results in non-small cell lung cancer patients, including cancer cell loss and increased T-cell infiltration, suggesting a potential new strategy for solid tumor immunotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combination IFNβ and Membrane-Stable CD40L Maximize Tumor Dendritic Cell Activation and Lymph Node Trafficking to Elicit Systemic T-cell Immunity. Zheng, H., Yu, X., Ibrahim, ML., et al.[2023]

The novel oncolytic virus VALO-D102, which encodes immunostimulatory molecules CD40L and OX40L, effectively activates both innate and adaptive immune responses against tumors, enhancing anti-cancer immunity.

In mouse models of melanoma, intratumoral administration of VALO-D102 significantly increased tumor-specific T cell responses and reduced tumor growth, especially when combined with anti-PD-1 therapy, demonstrating improved efficacy over either treatment alone.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Characterization of a novel OX40 ligand and CD40 ligand-expressing oncolytic adenovirus used in the PeptiCRAd cancer vaccine platform. Ylösmäki, E., Ylösmäki, L., Fusciello, M., et al.[2021]

In a trial involving 34 patients with recurrent malignant pleural mesothelioma, nivolumab demonstrated a disease control rate of 47% at 12 weeks, with 24% of patients achieving a partial response.

While nivolumab showed meaningful efficacy, it also had a manageable safety profile, with 76% of patients experiencing treatment-related adverse events, including fatigue and pruritus, and one treatment-related death due to pneumonitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Programmed Death 1 Blockade With Nivolumab in Patients With Recurrent Malignant Pleural Mesothelioma. Quispel-Janssen, J., van der Noort, V., de Vries, JF., et al.[2020]

The study developed measles vaccine strain vectors that deliver immunomodulators, showing that the vector MeVac FmIL-12 led to a remarkable 90% complete remission in established tumors in the MC38cea model.

MeVac FmIL-12 activates a strong immune response by enhancing natural killer and effector T cell activity, with CD8+ T cells being crucial for its effectiveness, highlighting its potential as a targeted immunovirotherapy approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oncolytic measles virus encoding interleukin-12 mediates potent antitumor effects through T cell activation. Veinalde, R., Grossardt, C., Hartmann, L., et al.[2021]

In a study of 34 Japanese patients with previously treated malignant pleural mesothelioma, nivolumab demonstrated a 3-year overall survival rate of 23.5% and a median overall survival of 17.3 months, indicating its long-term efficacy.

Nivolumab was well tolerated with no new safety concerns, and patient-reported outcomes remained stable throughout the treatment, suggesting it is a safe option for patients with this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Efficacy and Safety of Nivolumab in Japanese Patients With Malignant Pleural Mesothelioma: 3-Year Results of the MERIT Study. Fujimoto, N., Okada, M., Kijima, T., et al.[2022]

Nivolumab, an immune checkpoint inhibitor, demonstrated a 29% objective response rate in patients with advanced malignant pleural mesothelioma (MPM) who were resistant or intolerant to previous chemotherapy, indicating its potential as an effective second- or third-line treatment option.

The treatment was associated with manageable toxicity, as 94% of patients experienced adverse events, but the median overall survival was 17.3 months, suggesting that nivolumab can provide meaningful clinical benefits for this challenging condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Efficacy and Safety of Nivolumab: Results of a Multicenter, Open-label, Single-arm, Japanese Phase II study in Malignant Pleural Mesothelioma (MERIT). Okada, M., Kijima, T., Aoe, K., et al.[2019]

In a retrospective study of 11 patients with malignant pleural mesothelioma treated with nivolumab, 72.7% experienced immune-related adverse events (irAEs), which were linked to better treatment outcomes.

Patients with grade ≥2 irAEs had significantly longer progression-free survival (13.6 months) and overall survival (not reached) compared to those with milder irAEs, suggesting that monitoring and managing irAEs could enhance the effectiveness of nivolumab therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Correlation between immune-related adverse events and therapeutic effects of nivolumab in patients with malignant pleural mesothelioma. Yoneda, H., Nokihara, H., Mitsuhashi, A., et al.[2022]

In a study of 162 patients with advanced non-small-cell lung cancer (NSCLC) receiving nivolumab, an increase in the lymphocyte-to-monocyte ratio (LMR) by 10% or more after 4 weeks was linked to a higher response rate and longer survival, indicating its potential as a predictive marker for treatment efficacy.

The findings were consistent across both discovery and validation cohorts, suggesting that monitoring LMR changes could help determine whether to continue nivolumab therapy, while no similar correlation was found in patients treated with docetaxel.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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. Sekine, K., Kanda, S., Goto, Y., et al.[2022]

In a phase 2 trial involving 117 patients with advanced, refractory squamous non-small-cell lung cancer, nivolumab demonstrated a 14.5% objective response rate, indicating its potential effectiveness as a treatment option.

The safety profile of nivolumab was manageable, with 17% of patients experiencing severe treatment-related adverse events, suggesting that while there are risks, the benefits may outweigh them for patients with limited treatment options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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. Rizvi, NA., Mazières, J., Planchard, D., et al.[2022]

This study analyzed the pharmacokinetics of nivolumab in 34 Japanese patients with nonsmall cell lung cancer (NSCLC), revealing a mean clearance rate of 0.0064 L/h, which is important for understanding how the drug behaves in the body.

Factors such as serum albumin levels, estimated glomerular filtration rate, and treatment duration significantly influenced the drug's clearance, suggesting that these patient-specific characteristics should be considered when determining optimal dosing regimens.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Population Pharmacokinetics of Nivolumab in Japanese Patients with Nonsmall Cell Lung Cancer. Tohi, M., Irie, K., Mizuno, T., et al.[2023]

In a study of 1588 patients with nonsquamous NSCLC, nivolumab showed a higher objective response rate in patients with wild-type EGFR compared to those with EGFR-mutant tumors (19.6% vs. 8.8%), indicating that EGFR status influences treatment efficacy.

Never-smokers had a lower response rate to nivolumab (9.2%) compared to former and current smokers (21.5%), but among never-smokers, those with wild-type EGFR had a significantly better response (11.0%) than those with mutant EGFR (1.9%).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Italian Nivolumab Expanded Access Program in Nonsquamous Non-Small Cell Lung Cancer Patients: Results in Never-Smokers and EGFR-Mutant Patients. Garassino, MC., Gelibter, AJ., Grossi, F., et al.[2019]

In a real-world study of Canadian lung cancer patients treated with nivolumab, the median overall survival was 12.0 months, comparable to results from phase III clinical trials, despite the cohort including older patients and those with poorer prognoses.

The median time to treatment discontinuation was 3.45 months, consistent across various subgroups, indicating that nivolumab is effective and tolerable even in patients with more challenging health conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-world benefit of nivolumab in a Canadian non-small-cell lung cancer cohort. Juergens, RA., Mariano, C., Jolivet, J., et al.[2020]

References

1. United States pubmed.ncbi.nlm.nih.gov

Combination IFNβ and Membrane-Stable CD40L Maximize Tumor Dendritic Cell Activation and Lymph Node Trafficking to Elicit Systemic T-cell Immunity. [2023]

2. United States pubmed.ncbi.nlm.nih.gov

Characterization of a novel OX40 ligand and CD40 ligand-expressing oncolytic adenovirus used in the PeptiCRAd cancer vaccine platform. [2021]

3. United States pubmed.ncbi.nlm.nih.gov

Programmed Death 1 Blockade With Nivolumab in Patients With Recurrent Malignant Pleural Mesothelioma. [2020]

4. United States pubmed.ncbi.nlm.nih.gov

Oncolytic measles virus encoding interleukin-12 mediates potent antitumor effects through T cell activation. [2021]

5. United States pubmed.ncbi.nlm.nih.gov

Clinical Efficacy and Safety of Nivolumab in Japanese Patients With Malignant Pleural Mesothelioma: 3-Year Results of the MERIT Study. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

Clinical Efficacy and Safety of Nivolumab: Results of a Multicenter, Open-label, Single-arm, Japanese Phase II study in Malignant Pleural Mesothelioma (MERIT). [2019]

7. England pubmed.ncbi.nlm.nih.gov

Correlation between immune-related adverse events and therapeutic effects of nivolumab in patients with malignant pleural mesothelioma. [2022]

8. Ireland pubmed.ncbi.nlm.nih.gov

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]

9. England pubmed.ncbi.nlm.nih.gov

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]

10. United States pubmed.ncbi.nlm.nih.gov

Population Pharmacokinetics of Nivolumab in Japanese Patients with Nonsmall Cell Lung Cancer. [2023]

11. United States pubmed.ncbi.nlm.nih.gov

Italian Nivolumab Expanded Access Program in Nonsquamous Non-Small Cell Lung Cancer Patients: Results in Never-Smokers and EGFR-Mutant Patients. [2019]

12. Switzerland pubmed.ncbi.nlm.nih.gov

Real-world benefit of nivolumab in a Canadian non-small-cell lung cancer cohort. [2020]