IMA203/IMA203CD8 + Nivolumab for Cancer

(ACTengine Trial)

Recruiting at 14 trial locations

Overseen By Immatics US, Inc.

Age: 18+

Sex: Any

Trial Phase: Phase 1

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

476 Participants Needed

Trial Summary

What is the purpose of this trial?

The study purpose is to establish the safety and tolerability of IMA203/IMA203CD8 products with or without combination with nivolumab in patients with solid tumors that express preferentially expressed antigen in melanoma (PRAME).

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.

What data supports the effectiveness of the drug Nivolumab in cancer treatment?

Nivolumab has been shown to improve survival and response rates in patients with advanced non-small cell lung cancer and melanoma, compared to traditional chemotherapy. It is better tolerated and has a manageable side effect profile, making it an important option for these cancers. ^{1 2 3 4 5}

Is the treatment IMA203/IMA203CD8 + Nivolumab generally safe for humans?

Nivolumab, a part of the treatment, can cause immune-related side effects because it changes how the immune system works. These side effects can include inflammation in different parts of the body, like the intestines (colitis) and lungs (pneumonitis), and can be more common when used with other drugs like ipilimumab. ^{6 7 8 9 10}

What makes the IMA203/IMA203CD8 + Nivolumab treatment unique for cancer?

The IMA203/IMA203CD8 + Nivolumab treatment is unique because it combines a novel TCR-T cell therapy (IMA203/IMA203CD8) with Nivolumab, an immune checkpoint inhibitor, to enhance the immune system's ability to target and destroy cancer cells. This combination aims to improve the effectiveness of cancer treatment by leveraging both targeted cell therapy and immune system activation. ^{3 4 11 12 13}

Research Team

Cedrik Britten, M.D.

Principal Investigator

Immatics US, Inc.

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

Group I: Synovial Sarcoma Experimental Treatment 2 Interventions

IMA203CD8 monotherapy at dose levels confirmed to be safe

Group II: Ovarian/Uterine Experimental Treatment 2 Interventions

IMA203CD8 monotherapy at dose levels confirmed to be safe

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

IMA203CD8 monotherapy at dose levels confirmed to be safe

Group IV: Extension Cohort D Experimental Treatment 2 Interventions

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

Group V: Extension Cohort C Experimental Treatment 2 Interventions

IMA203CD8 at dose levels confirmed to be safe

Group VI: Extension Cohort B Experimental Treatment 3 Interventions

IMA203 at RP2D + nivolumab

Group VII: Extension Cohort AA Experimental Treatment 2 Interventions

IMA203 at anticipated final RP2D (flat dose)

Group VIII: Extension Cohort A Experimental Treatment 2 Interventions

IMA203 at RP2D

Group IX: Dose Escalation B Experimental Treatment 2 Interventions

Dose escalation of IMA203CD8

Group X: Dose Escalation A Experimental Treatment 2 Interventions

Dose escalation of IMA203

Who Is Running the Clinical Trial?

Immatics US, Inc.

Lead Sponsor

Trials

6

Recruited

1,100+

Findings from Research

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 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]

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]

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 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]

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]

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]

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]

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]

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]

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, 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]

References

1. England 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. [2020]

2. England pubmed.ncbi.nlm.nih.gov

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

3. New Zealand pubmed.ncbi.nlm.nih.gov

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

4. New Zealand pubmed.ncbi.nlm.nih.gov

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

5. France pubmed.ncbi.nlm.nih.gov

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

6. England pubmed.ncbi.nlm.nih.gov

An update on the safety of nivolumab for the treatment of advanced melanoma. [2021]

7. Singapore pubmed.ncbi.nlm.nih.gov

Management of immune checkpoint inhibitor-related adverse events: A review of case reports. [2021]

8. England pubmed.ncbi.nlm.nih.gov

Adverse events induced by nivolumab and ipilimumab combination regimens. [2022]

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

Side effects of immune-checkpoint inhibitors: Can multiple side effects be seen in a patient? [2022]

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

Adverse Events Induced by Nivolumab Plus Ipilimumab vs. Nivolumab Monotherapy among Cancer Patients: A Systematic Review and Meta-Analysis. [2022]

11. England 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. [2021]

12. England pubmed.ncbi.nlm.nih.gov

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

13. New Zealand pubmed.ncbi.nlm.nih.gov

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