IMGS-001 for Advanced Cancer

Recruiting at 3 trial locations

Overseen By Charles Schweizer, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: ImmunoGenesis

Must be taking: GnRH analogs

Must not be taking: Immunosuppressants, Interleukin-2

Disqualifiers: Autoimmune disorders, Heart disease, others

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

Compensation: Varies

Number of Visits: 4

105 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this Phase 1a/1b clinical trial is to test the safety of an investigational drug called IMGS-001 and to determine how well it can work in treating patients with advanced solid tumors that have come back or are not improving after receiving other drugs that are commonly used for their cancer. Phase 1a (Part 1) will test the safety of five different doses of IMGS-001 to use in further studies. Patients with cancer that have advanced or spread to other parts of the body following treatment with other available therapies will be treated in Part 1. Phase 1b (Part 2) will test two doses of IMGS-001 identified in Part 1 to further determine the safety and potential effectiveness in select cancer types.

Will I have to stop taking my current medications?

The trial requires that you stop taking any investigational or conventional anti-cancer drugs within 21 days before starting the trial. You also need to stop using immunosuppressive medications 14 days before starting, except for certain allowed ones. If you are on androgen deprivation therapy for prostate cancer, you must continue it.

What safety data exists for immune checkpoint inhibitors like IMGS-001 in humans?

Immune checkpoint inhibitors, which may include treatments like IMGS-001, are known to cause immune-related adverse events (irAEs), which can vary in severity. Most irAEs are mild and manageable with steroids, but some can be severe, requiring careful monitoring and management. ^{1 2 3 4 5}

How is the treatment IMGS-001 different from other treatments for advanced cancer?

IMGS-001 is unique because it may involve the use of patient-derived models like micro-organospheres (MOSs) to guide personalized treatment decisions, allowing for rapid assessment of tumor response to therapies, including immuno-oncology treatments, within a short timeframe. ^{6 7 8 9 10}

Eligibility Criteria

Adults with advanced solid tumors that have worsened after standard treatments can join this trial. They must have a specific type of tumor, adequate organ function, and no recent vaccines or other cancer therapies. People with certain blood counts, liver functions, and those who haven't had severe reactions to PD-1 or PD-L1 inhibitors may qualify.

Inclusion Criteria

My cancer tests positive for PD-L1.

To be included in cohorts with pre-existing immune checkpoint therapy, patients must fulfill the following requirements.

Your hemoglobin level is 9.0 g/dL or more.

Exclusion Criteria

I do not have severe autoimmune diseases but may have mild conditions like alopecia or celiac disease controlled by diet.

I haven't taken any cancer treatment or experimental drugs in the last 21 days.

I haven't used immunotherapy drugs like interleukin-2 or interferon in the last 28 days.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase 1a Treatment

Dose-escalation study to determine the safety, tolerability, and maximum tolerated dose (MTD) of IMGS-001 in patients with advanced solid tumors

21 days

Every 2 weeks

Phase 1b Treatment

Dose-expansion study to assess preliminary antitumor activity of IMGS-001 in five prespecified tumor cohorts

12 months

Every 2 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• IMGS-001

Trial Overview The trial is testing IMGS-001's safety at different doses for treating advanced solid tumors. Phase 1a finds the safest dose levels; Phase 1b tests these doses' effectiveness in select cancers with confirmed PD-L1 positive expression.

Participant Groups

Group I: Phase 1b Triple-negative Breast Cancer Experimental Treatment 1 Intervention

IMGS-001 will be administered every 2 weeks at the highest of the two doses of IMGS-001 that were selected for further evaluation in Phase 1a. Based on meeting minimum prespecified efficacy criteria, additional subjects may be enrolled and randomly assigned (1:1) to receive either the higher dose (Arm A) or a lower dose (Arm B) selected from Phase 1a.

Group II: Phase 1b Ovarian Cancer Experimental Treatment 1 Intervention

IMGS-001 will be administered every 2 weeks at the highest of the two doses of IMGS-001 that were selected for further evaluation in Phase 1a. Based on meeting minimum prespecified efficacy criteria, additional subjects may be enrolled and randomly assigned (1:1) to receive either the higher dose (Arm A) or a lower dose (Arm B) selected from Phase 1a.

Group III: Phase 1b Gastric or Esophageal Cancer Experimental Treatment 1 Intervention

IMGS-001 will be administered every 2 weeks at the highest of the two doses of IMGS-001 that were selected for further evaluation in Phase 1a. Based on meeting minimum prespecified efficacy criteria, additional subjects may be enrolled and randomly assigned (1:1) to receive either the higher dose (Arm A) or a lower dose (Arm B) selected from Phase 1a.

Group IV: Phase 1b Colorectal Cancer Experimental Treatment 1 Intervention

IMGS-001 will be administered every 2 weeks at the highest of the two doses of IMGS-001 that were selected for further evaluation in Phase 1a. Based on meeting minimum prespecified efficacy criteria, additional subjects may be enrolled and randomly assigned (1:1) to receive either the higher dose (Arm A) or a lower dose (Arm B) selected from Phase 1a.

Group V: Phase 1b Bladder Cancer Experimental Treatment 1 Intervention

IMGS-001 will be administered every 2 weeks at the highest of the two doses of IMGS-001 that were selected for further evaluation in Phase 1a. Based on meeting minimum prespecified efficacy criteria, additional subjects may be enrolled and randomly assigned (1:1) to receive either the higher dose (Arm A) or a lower dose (Arm B) selected from Phase 1a.

Group VI: Phase 1a Solid Tumors Experimental Treatment 1 Intervention

IMGS-001 will be administered in escalating doses, with a starting dose of 0.3 mg/kg every 2 weeks escalating up to a maximum dose of 15 mg/kg.

Who Is Running the Clinical Trial?

ImmunoGenesis

Lead Sponsor

Trials

3

Recruited

210+

Findings from Research

A comprehensive review of 41 randomized controlled trials involving 23,121 patients found that treatments combining chemotherapy with immune checkpoint inhibitors (ICIs) significantly increased the risk of treatment-related adverse events compared to ICI-only regimens.

Among the various ICI treatments, the combination of PD-L1 and CTLA-4 with chemotherapy had the highest risk of immune-related adverse events, with severe cases like myocarditis and pneumonitis showing notably high fatality rates, indicating the need for careful monitoring and management in patients receiving these therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Toxicity spectrum of immunotherapy in advanced lung cancer: A safety analysis from clinical trials and a pharmacovigilance system. Yan, YD., Zhao, Y., Zhang, C., et al.[2022]

Immune checkpoint inhibitors, such as those targeting CTLA-4, PD-1, and PD-L1, have become significant in cancer immunotherapy, showing promise in enhancing antitumor effects through both single-agent and combination therapies.

However, these therapies can lead to immune-related adverse events (irAEs), which vary in frequency and severity, highlighting the need for better understanding and management strategies for these side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immune-Related Adverse Events From Immune Checkpoint Inhibitors. Marrone, KA., Ying, W., Naidoo, J.[2022]

A dedicated inpatient service for managing high-grade immune-related adverse events (irAEs) from immune checkpoint inhibitors (ICIs) was established, successfully identifying 129 patients with significant irAEs over one year, primarily colitis and pneumonitis.

The service utilized electronic medical records to triage patients effectively, demonstrating a 26% readmission rate for recurrent irAEs, highlighting the need for ongoing monitoring and management of these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Novel platform leveraging electronic medical record (EMR) to triage patients admitted with high-grade immune-related adverse events (irAEs) to the immune-toxicity (ITOX) service. Abu-Shawer, O., Singh, P., Yenulevich, E., et al.[2021]

Immune-related adverse events (irAEs) are common but mostly mild and manageable with steroids in patients receiving immune checkpoint inhibitors, highlighting the importance of effective management strategies as these therapies become more widely used.

The study outlines a comprehensive 3-pronged strategy for managing irAEs, including a dedicated Immune Wellness Clinic for monitoring at-risk patients, a repository for supporting research, and an Immunotoxicity Tumor Board for handling severe cases, which can enhance patient care and safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Optimizing Care for Patients With Adverse Events From Immunotherapeutics. Sheehan, K., Price, C., Hafez, N.[2021]

Cancer immunotherapy has transformed treatment strategies, but the rise of immune-related adverse events (irAEs) poses significant challenges, limiting the benefits of these therapies.

A collaborative effort by experts has identified critical areas for research, including the need for better preclinical models and standardized data collection, to enhance understanding of irAEs and improve prevention and treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Development of preclinical and clinical models for immune-related adverse events following checkpoint immunotherapy: a perspective from SITC and AACR. Bayless, NL., Bluestone, JA., Bucktrout, S., et al.[2022]

In a study involving 33 patients with advanced gastrointestinal cancers, patient-derived tumor xenografts (PDTX) achieved a high engraftment rate of 75.8%, indicating their potential for personalized treatment strategies.

The drug effectiveness observed in PDTXs was 100% concordant with clinical responses, suggesting that PDTX can reliably predict how patients will respond to specific cancer treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A multicenter clinical study: personalized medication for advanced gastrointestinal carcinomas with the guidance of patient-derived tumor xenograft (PDTX). Cheng, Y., Qin, SK., Li, J., et al.[2022]

The study developed a rapid method using droplet emulsion microfluidics to create thousands of micro-organospheres (MOSs) from patient tissues, enabling timely assessment of drug responses in metastatic colorectal cancer patients within 14 days.

These MOSs not only model tumor responses to various therapies, including immuno-oncology treatments, but also maintain the original tumor environment, allowing for more accurate testing of potential treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patient-derived micro-organospheres enable clinical precision oncology. Ding, S., Hsu, C., Wang, Z., et al.[2023]

The study highlights the importance of understanding tumor heterogeneity, particularly the role of the epithelial-to-mesenchymal transition (EMT) in contributing to cancer metastasis and treatment resistance.

A novel multiplexed immunostaining protocol was developed to detect and quantify EMT states in tumors, which can help in assessing tumor heterogeneity and potentially guiding more effective patient treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Quantifying epithelial-mesenchymal heterogeneity and EMT scoring in tumor samples via tyramide signal amplification (TSA). Brown, MS., Abdollahi, B., Hassanpour, S., et al.[2023]

A six-plex multiplexed immunofluorescence (mIF) assay was optimized to effectively measure the PD-1/PD-L1 axis, achieving a 90% equivalence with traditional immunohistochemistry (IHC) methods across multiple sites.

The assay demonstrated high reproducibility and concordance in measuring immune cell densities and PD-L1 expression, with intersite concordance values averaging R2=0.88 for immune cell assessments, indicating its potential for use in precision immuno-oncology trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multi-institutional TSA-amplified Multiplexed Immunofluorescence Reproducibility Evaluation (MITRE) Study. Taube, JM., Roman, K., Engle, EL., et al.[2022]

Image-guided biopsies in advanced cancer patients were found to be safe, with major complications occurring in only 2.1% of cases, primarily involving pain and pneumothorax in lung biopsies.

The majority of tumor samples collected (74%) were of sufficient quality for biomarker discovery, allowing for effective next-generation sequencing (NGS) analysis, which is crucial for personalized cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Implementation of a Multicenter Biobanking Collaboration for Next-Generation Sequencing-Based Biomarker Discovery Based on Fresh Frozen Pretreatment Tumor Tissue Biopsies. Bins, S., Cirkel, GA., Gadellaa-Van Hooijdonk, CG., et al.[2022]

References

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

Toxicity spectrum of immunotherapy in advanced lung cancer: A safety analysis from clinical trials and a pharmacovigilance system. [2022]

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

Immune-Related Adverse Events From Immune Checkpoint Inhibitors. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Novel platform leveraging electronic medical record (EMR) to triage patients admitted with high-grade immune-related adverse events (irAEs) to the immune-toxicity (ITOX) service. [2021]

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

Optimizing Care for Patients With Adverse Events From Immunotherapeutics. [2021]

5. England pubmed.ncbi.nlm.nih.gov

Development of preclinical and clinical models for immune-related adverse events following checkpoint immunotherapy: a perspective from SITC and AACR. [2022]

6. Germany pubmed.ncbi.nlm.nih.gov

A multicenter clinical study: personalized medication for advanced gastrointestinal carcinomas with the guidance of patient-derived tumor xenograft (PDTX). [2022]

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

Patient-derived micro-organospheres enable clinical precision oncology. [2023]

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

Quantifying epithelial-mesenchymal heterogeneity and EMT scoring in tumor samples via tyramide signal amplification (TSA). [2023]

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

Multi-institutional TSA-amplified Multiplexed Immunofluorescence Reproducibility Evaluation (MITRE) Study. [2022]

10. England pubmed.ncbi.nlm.nih.gov

Implementation of a Multicenter Biobanking Collaboration for Next-Generation Sequencing-Based Biomarker Discovery Based on Fresh Frozen Pretreatment Tumor Tissue Biopsies. [2022]