IMA203/IMA203CD8 + Nivolumab for Cancer

(ACTengine Trial)

Recruiting at 18 trial locations

Overseen By Immatics US, Inc.

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Immatics US, Inc.

Must not be taking: Immunosuppressants, PD1/PD-L1 inhibitors

Disqualifiers: Other malignancies, Autoimmune, Cardiac, others

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

Compensation: Varies

Number of Visits: 1

Duration: 35 days

375 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test the safety and tolerability of a new treatment for solid tumors, which are masses of tissue that can occur in various organs. The treatment involves IMA203/IMA203CD8, a type of TCR-T cell therapy, used alone or with nivolumab, an immunotherapy drug. It targets individuals whose tumors express a protein commonly found in melanoma, a type of skin cancer. Those with solid tumors that have recurred or do not respond to current treatments, and who possess a specific genetic marker (HLA-A*02:01), might be suitable candidates. 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 innovative therapy.

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, if you have a serious autoimmune disease, you might be included if your condition is well controlled without immunosuppressive drugs. It's best to discuss your specific medications with the trial team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that IMA203 alone was well tolerated in earlier studies, with no very severe side effects reported. The treatment was manageable and did not cause major problems for patients.

For IMA203CD8, early data suggest it effectively targets cancer cells and boosts the immune system's response to tumors. It is generally well tolerated, similar to IMA203.

Nivolumab, another treatment in the trial, has FDA approval for various cancers. Serious side effects, such as urinary tract infections and kidney problems, occur in more than 2% of patients, though they are not common.

Overall, the treatments in this trial have demonstrated a reasonable safety profile based on existing data and approvals. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about IMA203/IMA203CD8 combined with Nivolumab because these treatments target cancer using innovative approaches. Unlike standard chemotherapies that attack rapidly dividing cells indiscriminately, IMA203/IMA203CD8 focus on enhancing the body's T-cell response to specifically target and destroy cancer cells. This method offers the potential for a more precise attack on tumors with fewer side effects. Additionally, the combination with Nivolumab, a checkpoint inhibitor, helps to further unleash the immune system's power by preventing cancer cells from evading immune detection. This dual approach represents a significant advancement in personalized cancer therapy, offering hope for improved outcomes in patients with challenging cancer types.

What evidence suggests that this trial's treatments could be effective for solid tumors?

Research has shown that IMA203 holds promise for treating solid tumors, with over half of the patients experiencing tumor shrinkage. Patients experienced lasting benefits, with the average response lasting more than a year. In this trial, some participants will receive IMA203 alone, while others will receive the next-generation IMA203CD8 therapy, which has also demonstrated strong anti-tumor effects with manageable side effects. Additionally, some participants will receive Nivolumab, which has proven effective in treating various cancers like melanoma and lung cancer by helping the immune system better attack cancer cells. Together, these treatments in the various trial arms aim to target and reduce solid tumors that express the PRAME protein. ^{2 3 6 7 8}

Who Is on the Research Team?

Cedrik Britten, M.D.

Principal Investigator

Immatics US, Inc.

Are You a Good Fit for This Trial?

This trial is for adults with solid tumors that no longer respond to standard treatments and express a specific antigen (PRAME). Participants must have an ECOG performance status of 0-1, indicating they are fully active or restricted in physically strenuous activity but ambulatory. They should not have other cancers within the last 3 years, serious autoimmune diseases, heart conditions, prior transplants, immune deficiencies, HIV/HBV/HCV infections with detectable viral load, brain metastases over 10 cm in size or severe reactions to similar drugs.

Inclusion Criteria

My solid tumor cancer is getting worse or not responding to treatment, and I've tried or can't have all standard treatments.

I am fully active or can carry out light work.

My HLA type matches the study requirements.

Exclusion Criteria

Concurrent severe and/or uncontrolled medical disease that could compromise participation in the study

I do not have HIV, active hepatitis B or C, nor am I currently being treated for hepatitis C.

History of or current immunodeficiency disease or prior treatment compromising immune function at the discretion of the treating physician

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Manufacturing

IMA203 or IMA203CD8 products are manufactured from the patients' white blood cells

Not specified

Treatment

Lymphodepletion with cyclophosphamide and fludarabine followed by IMA203/IMA203CD8 product infusion; IL-2 may be given until day 10; nivolumab administered in Extension Cohort B

35 days

Hospital admission for T-cell infusion

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 years

What Are the Treatments Tested in This Trial?

Interventions

• IMA203/IMA203CD8 Product
• Nivolumab

Trial Overview

The study tests IMA203/IMA203CD8 products alone or combined with nivolumab on patients whose tumors express PRAME. It aims to determine the safety and tolerability of these therapies. The trial will measure how well the disease responds according to RECIST criteria which assess tumor shrinkage and growth.

How Is the Trial Designed?

Group I: Uveal Melanoma Experimental Treatment 2 Interventions

IMA203 at RP2D

Group II: Rare Cancers Experimental Treatment 2 Interventions

IMA203CD8 monotherapy at dose levels confirmed to be safe

Group III: Ovarian Experimental Treatment 2 Interventions

IMA203CD8 monotherapy at dose levels confirmed to be safe

Group IV: Head and Neck, Lung, and Triple Negative Breast Cancer Experimental Treatment 2 Interventions

IMA203CD8 monotherapy at dose levels confirmed to be safe

Group V: Extension Cohort D Experimental Treatment 2 Interventions

IMA203CD8 at dose levels confirmed to be safe; without IL-2

Group VI: Extension Cohort C Experimental Treatment 2 Interventions

IMA203CD8 at dose levels confirmed to be safe

Group VII: Extension Cohort B (closed to enrollment) Experimental Treatment 2 Interventions

IMA203 at RP2D + nivolumab

Group VIII: Extension Cohort AA Experimental Treatment 2 Interventions

IMA203 at final RP2D (flat dose)

Group IX: Extension Cohort A Experimental Treatment 2 Interventions

IMA203 at RP2D

Group X: Endometrial Experimental Treatment 2 Interventions

IMA203CD8 monotherapy at dose levels confirmed to be safe

Group XI: Dose Escalation B Experimental Treatment 2 Interventions

Dose escalation of IMA203CD8

Group XII: Dose Escalation A (closed to enrollment) Experimental Treatment 2 Interventions

Dose escalation of IMA203

Who Is Running the Clinical Trial?

Immatics US, Inc.

Lead Sponsor

Trials

6

Recruited

1,100+

Published Research Related to This Trial

Nivolumab, a PD-1 inhibitor, has demonstrated significant safety and efficacy in treating various advanced solid tumors, including melanoma and lung cancer, based on multiple high-level studies.

Future research should aim to identify predictive biomarkers for treatment response and explore the potential of combining nivolumab with other therapies, as well as determining the best treatment strategies and duration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An update on the pharmacodynamics, pharmacokinetics, safety and clinical efficacy of nivolumab in the treatment of solid cancers. Wong, AC., Ma, B.[2018]

Nivolumab, an immune checkpoint inhibitor, significantly improved overall survival and progression-free survival compared to docetaxel in patients with advanced squamous non-small cell lung cancer (NSCLC) in the CheckMate 017 trial.

Nivolumab was better tolerated than docetaxel, with manageable adverse effects, making it a promising treatment option for patients who have already undergone chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab: a review in advanced squamous non-small cell lung cancer. Keating, GM.[2022]

Nivolumab, an immune checkpoint inhibitor, shows strong antitumor activity but is associated with immune-related adverse events that can affect patient safety and treatment continuation, necessitating careful monitoring.

Long-term safety data, including a 5-year follow-up, suggests that nivolumab can be safely administered to various challenging patient subgroups, but identifying biomarkers for severe toxicity could improve patient selection for this therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An update on the safety of nivolumab for the treatment of advanced melanoma. Czarnecka, AM., Rutkowski, P.[2021]

Nivolumab, a monoclonal antibody used to treat recurrent renal cell carcinoma, can cause significant immune-related adverse events, such as hepatitis and adrenalitis, as seen in a case study of a 66-year-old male patient.

Prompt recognition and management of these side effects are crucial; in this case, the patient's hepatitis improved with methylprednisolone, and adrenalitis was treated with fludrocortisone, leading to normalization of symptoms and electrolyte levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Side effects of immune-checkpoint inhibitors: Can multiple side effects be seen in a patient? Özyurt, E., Özçelik, S., Sürmeli, H., et al.[2022]

A systematic review of 14 randomized controlled trials found that combining nivolumab (NIVO) with ipilimumab (IPI) significantly increases the risk of treatment-related adverse events (TRAEs) compared to NIVO alone, with an overall risk ratio of 1.11 for any grade TRAEs and 1.95 for severe (grade 3 or 4) TRAEs.

Specific adverse events were notably higher with the combination therapy, including colitis (RR = 4.52), pneumonitis (RR = 3.06), and diarrhea (RR = 1.68), indicating that while the combination may be effective, it comes with increased safety concerns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse Events Induced by Nivolumab Plus Ipilimumab vs. Nivolumab Monotherapy among Cancer Patients: A Systematic Review and Meta-Analysis. Kamat, S., Patel, J., Brown, BR., et al.[2022]

Nivolumab significantly improves response rates and survival in patients with metastatic melanoma, especially in those previously treated with ipilimumab, compared to chemotherapy and ipilimumab alone.

The combination of nivolumab with a lower dose of ipilimumab is better tolerated than the standard dose combination, suggesting a safer treatment option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cost-effectiveness of nivolumab in advanced melanoma: a drug review. Specenier, P.[2021]

In a real-world study of 371 patients with advanced squamous non-small cell lung cancer (NSCLC) receiving nivolumab, the objective response rate was 18% and the median overall survival was 7.9 months, indicating that nivolumab is effective in this patient population.

The safety profile of nivolumab was favorable, with only 29% of patients experiencing any-grade adverse events and no treatment-related deaths, suggesting that its use in routine clinical practice aligns with findings from controlled clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Italian Cohort of Nivolumab Expanded Access Program in Squamous Non-Small Cell Lung Cancer: Results from a Real-World Population. Crinò, L., Bidoli, P., Delmonte, A., et al.[2020]

Nivolumab significantly improved one-year survival rates in patients with inoperable or metastatic BRAF V600-negative melanoma compared to dacarbazine (73% vs. 42%), indicating its efficacy as a first-line treatment option.

While nivolumab shows promise for treatment-naive patients, it does not demonstrate a clear advantage over other treatments for patients who have already received therapy, and it carries a risk of serious immunological side effects in 9% of patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab (OPDIVOO) BRAF V600 mutation-negative metastatic or inoperable melanoma: survival advantage. [2019]

In a meta-analysis of 48 studies involving 4,677 patients, the combination of nivolumab and ipilimumab resulted in a high incidence of adverse events (AEs), with 81.3% of patients experiencing any AE and 40.6% experiencing grade 3 or higher AEs.

The regimen of nivolumab 3 mg/kg plus ipilimumab 1 mg/kg (N3I1) was found to cause significantly fewer AEs, including serious AEs, compared to the regimen of nivolumab 1 mg/kg plus ipilimumab 3 mg/kg (N1I3), suggesting that N3I1 may be a safer option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse events induced by nivolumab and ipilimumab combination regimens. Somekawa, K., Horita, N., Kaneko, A., et al.[2022]

In a study of 119 patients with metastatic non-small cell lung cancer (mNSCLC) treated with nivolumab, the presence of specific HLA-A alleles (HLA-A*01 and A*02) was linked to better progression-free survival (PFS) and overall survival (OS), suggesting these alleles may serve as biomarkers for treatment efficacy.

Patients lacking these HLA-A alleles had significantly poorer outcomes, with a PFS of only 7.5 months compared to 22.6 months for HLA-A*01-positive patients, highlighting the importance of HLA genotype in predicting responses to PD-1 blockade therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Distinctive germline expression of class I human leukocyte antigen (HLA) alleles and DRB1 heterozygosis predict the outcome of patients with non-small cell lung cancer receiving PD-1/PD-L1 immune checkpoint blockade. Correale, P., Saladino, RE., Giannarelli, D., et al.[2021]

Immune checkpoint inhibitors, such as pembrolizumab and nivolumab, can lead to immune-related adverse events (irAEs) due to their mechanism of enhancing the immune response against cancer, which can sometimes mistakenly target healthy tissues.

This study reviewed 128 reports involving 239 cases of toxicities associated with these treatments, highlighting the need for careful management of irAEs, as there is currently no standardized approach based on prospective trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Management of immune checkpoint inhibitor-related adverse events: A review of case reports. Si, X., Song, P., Ni, J., et al.[2021]

Nivolumab, a monoclonal antibody targeting the programmed death receptor-1, has shown promising efficacy in treating advanced malignant melanoma, with nearly 25% of patients achieving a partial tumor response in a phase II trial involving previously treated stage III/IV patients.

The treatment demonstrated a durable clinical benefit, with a median progression-free survival of 172 days and an acceptable safety profile, as less than 18% of patients experienced severe adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab: a review of its use in patients with malignant melanoma. Deeks, ED.[2021]

Nivolumab (Opdivo) significantly improves overall survival and response rates in previously-treated patients with advanced nonsquamous non-small cell lung cancer (NSCLC) compared to docetaxel, as shown in the CheckMate 057 trial.

Nivolumab has a manageable adverse event profile and is better tolerated than docetaxel, making it a valuable treatment option for patients who have progressed after chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab: A Review in Advanced Nonsquamous Non-Small Cell Lung Cancer. Keating, GM.[2018]

Citations

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The study purpose is to establish the safety and tolerability of IMA203/IMA203CD8 products with or without combination with nivolumab in patients with solid ...