IMM-6-415 for Solid Tumors

No longer recruiting at 4 trial locations

Overseen By IMM-6-415 Study Team

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Immuneering Corporation

Disqualifiers: CNS metastases, Cardiac disease, Diabetes, RVO, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 48 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment called IMM-6-415, an experimental therapy for individuals with advanced or spreading solid tumors. The focus is on tumors with specific gene mutations, such as RAS or RAF, which are linked to cancer growth. Researchers aim to determine the optimal dose and evaluate the treatment's effectiveness against these tumors. Individuals who have tried standard treatments without success and have a confirmed mutation might be suitable candidates for this study. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new therapy.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial team or your doctor.

Is there any evidence suggesting that IMM-6-415 is likely to be safe for humans?

Research shows that IMM-6-415 looks promising in early safety tests. In past animal studies, this treatment slowed tumor growth without major safety issues. More importantly, recent updates indicate that IMM-6-415, when tested alone, was generally well-tolerated at all doses tried so far. Most participants did not experience serious side effects. While this is encouraging, the treatment remains in early testing stages, so more information is needed to fully understand its safety in humans. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for solid tumors, which often rely on chemotherapy and radiation, IMM-6-415 offers a fresh approach with its unique mechanism of action. This experimental treatment is designed to target and disrupt specific pathways within tumor cells, potentially reducing their growth and spread. Researchers are excited about IMM-6-415 because it not only aims to be more precise in attacking cancer cells but may also minimize damage to healthy cells, which could lead to fewer side effects than traditional therapies. Additionally, IMM-6-415's structure may allow it to work in cases where other treatments have failed, offering hope for patients with resistant forms of solid tumors.

What evidence suggests that IMM-6-415 might be an effective treatment for solid tumors?

Research has shown that IMM-6-415, the investigational treatment in this trial, has promising results in early studies for tumors with RAS or RAF mutations. In animal studies, this treatment significantly slowed the growth of these tumors, both alone and in combination with other drugs. IMM-6-415 targets a molecule called oncostatin M, which plays a role in tumor growth. As a Deep Cyclic Inhibitor, it blocks the MAPK pathway, often active in cancer cells. These early findings suggest that IMM-6-415 may help slow or shrink tumors in humans with similar genetic mutations. ^{1 2 6 7 8}

Who Is on the Research Team?

Vinny Hayreh, MD

Principal Investigator

Immuneering Corporation

Are You a Good Fit for This Trial?

This trial is for adults with advanced or metastatic solid tumors, like melanoma and lung cancer, that have specific genetic changes called RAS or RAF mutations. Participants should not have had prior treatment with IMM-6-415.

Inclusion Criteria

I am fully active or can carry out light work.

My cancer is advanced, cannot be surgically removed, and has specific RAS or RAF mutations.

I've had at least one standard treatment for my advanced cancer and can't handle or benefit from other treatments.

Exclusion Criteria

I have a history of serious eye conditions or am at risk for retinal vein blockage.

I have heart problems that affect my daily activities.

I had hepatitis B but don't need treatment anymore, or I had hepatitis C but it's undetectable now.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants self-administer IMM-6-415 daily for up to 16 cycles (21-day cycles) to assess safety, tolerability, and anti-tumor activity

48 weeks

Regular monitoring visits during cycles

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Long-term Follow-up

Participants are monitored for progression-free survival and overall survival

Up to approximately 2 years

What Are the Treatments Tested in This Trial?

Interventions

• IMM-6-415

Trial Overview

The study tests a new drug named IMM-6-415 to find the safest dose and see how well it works against certain cancers. It's an early-stage trial where doses increase gradually to monitor effects on patients' tumors.

How Is the Trial Designed?

Group I: IMM-6-415 Experimental Treatment 1 Intervention

Dose Escalation and Dose Expansion

Who Is Running the Clinical Trial?

Immuneering Corporation

Lead Sponsor

Trials

2

Recruited

450+

Published Research Related to This Trial

Oncostatin M (OSM) has been identified as a significant factor in promoting tumor growth and metastasis, particularly in squamous cell carcinoma (SCC), by creating a feedback loop that enhances its own production and that of its receptor (OSMR).

Targeting the OSM/OSMR signaling pathway could provide new therapeutic strategies to combat aggressive cancer behaviors and improve treatment outcomes in SCC and potentially other cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Breaking the oncostatin M feed-forward loop to suppress metastasis and therapy failure. Smigiel, J., Parvani, JG., Tamagno, I., et al.[2019]

In a phase 3 trial involving 355 patients with advanced soft-tissue sarcomas, the combination of ombrabulin and cisplatin showed a slight but significant improvement in progression-free survival compared to placebo plus cisplatin, with a median of 1.54 months versus 1.41 months.

Despite the improved survival, the ombrabulin group experienced more severe adverse events, including higher rates of neutropenia and thrombocytopenia, leading to concerns about its overall clinical benefit as a treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ombrabulin plus cisplatin versus placebo plus cisplatin in patients with advanced soft-tissue sarcomas after failure of anthracycline and ifosfamide chemotherapy: a randomised, double-blind, placebo-controlled, phase 3 trial. Blay, JY., Pápai, Z., Tolcher, AW., et al.[2018]

AMG 232, an oral selective MDM2 inhibitor, demonstrated acceptable safety up to a dose of 240 mg, with mild to moderate adverse effects such as diarrhea and fatigue, and dose-limiting toxicities including thrombocytopenia and neutropenia in a study involving 107 patients with advanced solid tumors or multiple myeloma.

While there were no complete responses to treatment, stable disease was observed in several patients across different tumor types, indicating potential efficacy in maintaining disease stability, particularly in well-differentiated liposarcomas and other solid tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 1 study of the MDM2 inhibitor AMG 232 in patients with advanced P53 wild-type solid tumors or multiple myeloma. Gluck, WL., Gounder, MM., Frank, R., et al.[2022]

In a study of 72 rectal cancer patients undergoing neoadjuvant chemoradiotherapy, low PD-L1 expression (≤1% tumor proportion score) was linked to significantly poorer survival outcomes, with a median survival of 56.7 months compared to not reached for those with higher expression.

The study found that PD-L1 expression prior to treatment was an independent prognostic factor for survival, suggesting that assessing PD-L1 levels could help predict patient outcomes and guide treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of PD-L1 Scores and Changes on Clinical Outcome in Rectal Cancer Patients Undergoing Neoadjuvant Chemoradiotherapy. Huemer, F., Klieser, E., Neureiter, D., et al.[2020]

AMG232, an MDM-2 inhibitor, significantly enhances the effectiveness of Doxorubicin in inducing apoptosis in NALM-6 leukemia cells, suggesting a potential strategy to mitigate Doxorubicin's cardiotoxicity while improving its anti-leukemic effects.

The combination treatment of AMG232 and Doxorubicin not only increases apoptosis through caspase-3 activation but also alters cell cycle progression and boosts the expression of key apoptosis and autophagy-related genes, indicating a multifaceted mechanism of action.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

AMG-232, a New Inhibitor of MDM-2, Enhance Doxorubicin Efficiency in Pre-B Acute Lymphoblastic Leukemia Cells. Ghotaslou, A., Samii, A., Boustani, H., et al.[2023]

Brigimadlin, an oral MDM2-p53 antagonist, demonstrated a manageable safety profile in a phase Ia study involving 54 patients with advanced solid tumors, with the most common side effects being nausea (74.1%) and vomiting (51.9%).

The drug showed promising preliminary efficacy, with an overall response rate of 11.1% and a disease control rate of 74.1%, particularly in patients with well-differentiated or dedifferentiated liposarcoma, where disease control rates reached 100% and 75%, respectively.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The MDM2-p53 Antagonist Brigimadlin (BI 907828) in Patients with Advanced or Metastatic Solid Tumors: Results of a Phase Ia, First-in-Human, Dose-Escalation Study. LoRusso, P., Yamamoto, N., Patel, MR., et al.[2023]

Pepleomycin (NK631) demonstrated approximately double the antimicrobial activity compared to bleomycin (BLM) against both gram-positive and gram-negative bacteria, indicating its potential as a more effective antimicrobial agent.

NK631 showed superior antitumor effects in various cancer models, particularly against lymph node metastasis and gastric carcinoma, while exhibiting significantly lower pulmonary toxicity compared to BLM, making it a promising alternative in cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Studies on antitumor activities and pulmonary toxicity of pepleomycin sulfate (NK631) (author's transl)]. Ebihara, K., Ekimoto, H., Itchoda, Y., et al.[2016]

In a meta-analysis of 39 studies involving 3,680 patients with bone and soft tissue sarcomas, high PD-L1 expression was found to predict poorer overall survival and increased rates of metastasis, indicating its potential as a prognostic biomarker.

The analysis also revealed that PD-L1 overexpression is associated with more advanced tumor grades and higher T lymphocyte infiltration, suggesting that it may play a significant role in the tumor's immune environment and progression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prognostic Value of Programmed Cell Death 1 Ligand-1 in Patients With Bone and Soft Tissue Sarcomas: A Systemic and Comprehensive Meta-Analysis Based on 3,680 Patients. Wang, F., Yu, T., Ma, C., et al.[2020]

In a large study of 48,782 cancer cases, PD-L1 expression was more commonly found in immune cells than in tumor cells, and there was a strong correlation between PD-L1 expression and other biomarkers like CD274 gene amplification, microsatellite instability (MSI), and tumor mutational burden (TMB).

Over half of the cases (50.3%) tested positive for at least one biomarker related to immunotherapy response, highlighting the potential for personalized treatment strategies, particularly for the PD-L1+/TMB+ subset, which may respond best to immunotherapy, though further clinical trials are needed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A pan-cancer analysis of PD-L1 immunohistochemistry and gene amplification, tumor mutation burden and microsatellite instability in 48,782 cases. Huang, RSP., Haberberger, J., Severson, E., et al.[2023]

In a study of 127 colorectal carcinoma cases, PD-L1 expression was evaluated using three different scoring systems, revealing that the Tumor Percentage Score (TPS) had the strongest correlation with clinicopathologic features and patient demographics.

Interestingly, PD-L1-negative cases showed a trend towards better survival in the first 60 months post-surgery when assessed by the TPS method, suggesting that PD-L1 status may influence treatment decisions and outcomes in CRC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

PD-L1 Expression in Colorectal Carcinoma: A Comparison of 3 Scoring Methods in a Cohort of Jordanian Patients. Awad, HA., Sughayer, MA., Obeid, JM., et al.[2023]

Citations

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NCT06208124 | A Study of IMM-6-415 in RAS/RAF Mutant ...

This is a FIH, ascending dose study to characterize the safety, tolerability, optimal dose and preliminary anti-tumor activity of IMM-6-415 in participants with ...

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ir.immuneering.com/news-releases/news-release-details/immuneering-announces-first-patient-dosed-its-phase-12a-trial

Immuneering Announces First Patient Dosed in its Phase 1 ...

In animal studies, IMM-6-415 strongly inhibited the growth of tumors with RAF or RAS mutations, as both a monotherapy and in combinations.

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withpower.com/trial/phase-2-melanoma-1-2024-6e12d

IMM-6-415 for Solid Tumors · Info for Participants

What data supports the effectiveness of the drug IMM-6-415 for solid tumors? The research suggests that targeting oncostatin M (OSM), a molecule involved in ...

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ir.immuneering.com

ir.immuneering.com/news-releases/news-release-details/immuneering-presents-preclinical-data-demonstrating-encouraging

Press Release Details

In combination with encorafenib, IMM-6-415 achieved a greater TGI in vivo than the combination of encorafenib plus binimetinib in BRAFV600E ...

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synapse.patsnap.com

synapse.patsnap.com/article/first-patient-receives-imm-6-415-in-phase-12a-solid-tumor-trial

First Patient Receives IMM-6-415 in Phase 1/2a Solid ...

This Deep Cyclic Inhibitor (DCI) of the MAPK pathway has shown promising results in preclinical studies, where it significantly suppressed tumor ...

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clin.larvol.com

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A Study of IMM-6-415 in RAS/RAF Mutant Solid Tumors

"Near-Term Milestone Expectations:...IMM-6-415: Initial PK, PD and safety data from the Phase 1 portion of the Company's Phase 1/2a trial is expected by year ...

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immuneering.gcs-web.com

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Immuneering Reports Second Quarter 2024 Financial Results ...

IMM-6-415 is an oral, twice-daily Deep Cyclic Inhibitor currently in a Phase 1/2a trial in patients with advanced solid tumors harboring RAS or ...

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imrx-20250107

The Company also announced that, as of December 23, 2024, IMM-6-415 monotherapy was observed to be generally well tolerated at all tested dose ...