IMM-6-415 for Solid Tumors

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

240 Participants Needed

Trial Summary

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.

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 cancer growth and spread, could help reduce aggressive cancer behavior and therapy failure, which might be relevant to the effectiveness of IMM-6-415 if it targets similar pathways. ^{1 2 3 4 5}

What safety data exists for the treatment IMM-6-415 in humans?

AMG 232, which may be related to IMM-6-415, was tested in a study with patients having advanced solid tumors or multiple myeloma. It was generally safe up to a dose of 240 mg, with some patients experiencing mild to moderate side effects like diarrhea, nausea, and fatigue. Serious side effects included low platelet counts (thrombocytopenia) and low white blood cell counts (neutropenia). ^{6 7 8 9 10}

What is the purpose of this trial?

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 advanced or metastatic solid tumors harboring RAS or RAF oncogenic mutations.

Research Team

Vinny Hayreh, MD

Principal Investigator

Immuneering Corporation

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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 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]

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 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]

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]

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]

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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

Breaking the oncostatin M feed-forward loop to suppress metastasis and therapy failure. [2019]

2. Switzerland 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. [2020]

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

PD-L1 Expression in Colorectal Carcinoma: A Comparison of 3 Scoring Methods in a Cohort of Jordanian Patients. [2023]

4. United States 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. [2023]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Impact of PD-L1 Scores and Changes on Clinical Outcome in Rectal Cancer Patients Undergoing Neoadjuvant Chemoradiotherapy. [2020]

6. Iran pubmed.ncbi.nlm.nih.gov

AMG-232, a New Inhibitor of MDM-2, Enhance Doxorubicin Efficiency in Pre-B Acute Lymphoblastic Leukemia Cells. [2023]

7. United States 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. [2022]

8. United States 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. [2023]

9. England 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. [2018]

10. Japan pubmed.ncbi.nlm.nih.gov

[Studies on antitumor activities and pulmonary toxicity of pepleomycin sulfate (NK631) (author's transl)]. [2016]