IMA203/IMA203CD8 + Nivolumab for Cancer
(ACTengine Trial)
Recruiting in Palo Alto (17 mi)
+13 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 1
Recruiting
Sponsor: Immatics US, Inc.
Must not be taking: Immunosuppressants, PD1/PD-L1 inhibitors
Disqualifiers: Other malignancies, Autoimmune, Cardiac, others
No Placebo Group
Breakthrough Therapy
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?
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.678910
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.34111213
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.
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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
See 11 more
Trial 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 (CAR T-cell Therapy)
- Nivolumab (Checkpoint Inhibitor)
Trial OverviewThe 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
10Treatment groups
Experimental Treatment
Group I: Synovial SarcomaExperimental Treatment2 Interventions
IMA203CD8 monotherapy at dose levels confirmed to be safe
Group II: Ovarian/UterineExperimental Treatment2 Interventions
IMA203CD8 monotherapy at dose levels confirmed to be safe
Group III: Head and Neck, Lung, and Triple Negative Breast CancerExperimental Treatment2 Interventions
IMA203CD8 monotherapy at dose levels confirmed to be safe
Group IV: Extension Cohort DExperimental Treatment2 Interventions
IMA203CD8 at dose levels confirmed to be safe; without IL-2
Group V: Extension Cohort CExperimental Treatment2 Interventions
IMA203CD8 at dose levels confirmed to be safe
Group VI: Extension Cohort BExperimental Treatment3 Interventions
IMA203 at RP2D + nivolumab
Group VII: Extension Cohort AAExperimental Treatment2 Interventions
IMA203 at anticipated final RP2D (flat dose)
Group VIII: Extension Cohort AExperimental Treatment2 Interventions
IMA203 at RP2D
Group IX: Dose Escalation BExperimental Treatment2 Interventions
Dose escalation of IMA203CD8
Group X: Dose Escalation AExperimental Treatment2 Interventions
Dose escalation of IMA203
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Fox Chase Cancer CenterPhiladelphia, PA
Columbia University Medical CenterNew York, NY
University of Miami Hospital and ClinicsMiami, FL
University of Pittsburgh Medical CenterPittsburgh, PA
More Trial Locations
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Who Is Running the Clinical Trial?
Immatics US, Inc.Lead Sponsor
References
Italian Cohort of Nivolumab Expanded Access Program in Squamous Non-Small Cell Lung Cancer: Results from a Real-World Population. [2020]Nivolumab has shown a survival benefit compared with docetaxel as second-line treatment for patients with previously treated advanced squamous non-small cell lung cancer (NSCLC) in a randomized phase III trial. The experiences of patients and physicians in routine clinical practice are often different from those in a controlled clinical trial setting. We present data from the entire Italian cohort of patients with squamous NSCLC enrolled in a worldwide nivolumab NSCLC expanded access program.
Cost-effectiveness of nivolumab in advanced melanoma: a drug review. [2021]Introduction: The immune checkpoint inhibitors, including nivolumab, and targeted agents have dramatically improved the outcome for patients with unresectable advanced melanoma. Areas covered: This is a narrative review of the published evidence on nivolumab in metastatic melanoma. Expert opinion: In ipilimumab pre-treated patients (CheckMate 037), nivolumab was associated with a higher response rate and a longer duration of response when compared to chemotherapy. In previously untreated patients, nivolumab improves survival when compared to chemotherapy (CheckMate 066) or to ipilimumab (CheckMate 067). The combination of nivolumab and ipilimumab also improves survival when compared to ipilimumab (CheckMate 067). CheckMate 067 was not designed to compare the nivolumab-ipilimumab combination to nivolumab alone. A modified regimen using a lower dose of ipilimumab in combination with standard dose nivolumab is better tolerated than nivolumab in combination with standard dose ipilimumab (CheckMate 511). In patients with previously untreated metastatic melanoma, the anti-PD-1 monoclonal antibodies nivolumab and pembrolizumab improve survival when compared to ipilimumab. Nivolumab is equally active in BRAF mutated and BRAF wild type melanoma. The optimal sequence of checkpoint inhibitors and BRAF/MEK inhibitors in BRAF mutated patients has not been established.
Nivolumab: A Review in Advanced Nonsquamous Non-Small Cell Lung Cancer. [2018]The programmed death (PD)-1 immune checkpoint inhibitor nivolumab (Opdivo(®)) is approved in the USA for the treatment of patients with metastatic non-small cell lung cancer (NSCLC) who have progression on or after platinum-based chemotherapy and in the EU for the treatment of adults with locally advanced or metastatic NSCLC after prior chemotherapy. In previously-treated patients with advanced nonsquamous NSCLC, overall survival was significantly prolonged and the overall response rate was significantly higher in patients who received intravenous nivolumab 3 mg/kg every 2 weeks versus intravenous docetaxel in the pivotal CheckMate 057 trial. Progression-free survival did not significantly differ between patients receiving nivolumab and those receiving docetaxel. Intravenous nivolumab had a manageable adverse event profile (including immune-mediated adverse events) and was better tolerated than docetaxel in the CheckMate 057 trial. Thus, nivolumab is an important new option for use in previously-treated patients with advanced nonsquamous NSCLC.
Nivolumab: a review in advanced squamous non-small cell lung cancer. [2022]Nivolumab (Opdivo(®); Nivolumab BMS™) was the first programmed death (PD)-1 immune checkpoint inhibitor to be approved for use in advanced, squamous non-small cell lung cancer (NSCLC) following prior chemotherapy. In the pivotal CheckMate 017 trial, intravenous nivolumab 3 mg/kg every 2 weeks was associated with significantly better overall survival and progression-free survival and a significantly higher overall response rate than intravenous docetaxel in the second-line treatment of advanced, squamous NSCLC. Nivolumab was also better tolerated than docetaxel in CheckMate 017, and its adverse event profile (which included immune-mediated adverse events) was manageable. In conclusion, nivolumab represents an important advance in previously-treated, advanced, squamous NSCLC.
Nivolumab (OPDIVOO) BRAF V600 mutation-negative metastatic or inoperable melanoma: survival advantage. [2019]Existing drugs are poorly effective in patients with inoperable or meta- static melanoma without a mutation in the BRAF gene at position V600. The first-line treatment of choice for patients with BRAF V600-positive melanoma is a combination of dabrafenib (a BRAF inhibitor) and trametinib. Nivolumab is a human monoclonal antibody designed to block receptors for PD-1 (programmed cell death-1) and thus to enhance T lymphocyte activity, especially against tumour cells. Nivolumab has been authorised in Europe as monotherapy for patients with inoperable or metastatic melanoma, regardless of BRAFV600 status. Nivolumab has not been compared with the dabrafenib + trametinib combination in patients with BRAF V600-positive melanoma. A randomised double-blind trial ver- sus dacarbazine involved 418 patients with inoperable or metastatic BRAF V600-negative melanoma who had not yet received medication for this stage of the disease.The trial was halted prematurely when an unscheduled analysis showed an improvement in one-year survival with nivolumab compared to dacarbazne(73% versus 42%, p
An update on the safety of nivolumab for the treatment of advanced melanoma. [2021]Introduction: Due to its unique mechanism of action as an immune checkpoint inhibitor, nivolumab has high antitumor activity, but at the same time this mechanism is responsible for immune-related adverse events that may limit patients' safety and therapy continuation.Areas covered: Long-term safety of nivolumab including 5-year follow-up, safety of nivolumab treatment after ipilimumab therapy, safety of nivolumab in challenging subgroups (elderly, patients with brain metastases, patients with autoimmune disorders), safety of nivolumab in with rare melanoma subtypes (including mucosal melanoma), as well as specificity of AEs reported for nivolumab treatment in melanoma patients in comparison to other cancer types and other immunotherapy molecules, and impact of AEs on response rates and PFS on nivolumab treatment are discussed.Expert opinion: Search for biomarkers that would help us to identify patient populations that may suffer from severe nivolumab toxicity could help in selecting patients that should not be treated with this type of therapy. Novel combinations and immunotherapy drugs including use of NKTR-214 (IL-2 pathway), lymphocyte-activation gene 3 (LAG-3), local injections of talimogene laherparepvec (T-VEC), or systemic use of T-cell receptors agonists such as OX40, CD137, ICOS-1, could provide regimens with limited toxicity and higher activity.
Management of immune checkpoint inhibitor-related adverse events: A review of case reports. [2021]Immune checkpoint inhibitors represent a major breakthrough in cancer therapy. Immune-related adverse events (irAEs) may occur during treatment due to their unique mechanism of action. Management of irAEs is based on clinical experience because it is not easy to conduct prospective trials to evaluate the best treatment strategy. Using a combination of search terms in the PubMed and Embase databases, we reviewed all cases in the English language citing toxicities associated with either pembrolizumab, nivolumab, ipilimumab, atezolizumab, tremelimumab, durvalumab, avelumab or any combination of these agents published before 20 May 2019. A total of 128 reports with 239 cases were included in the study. Here, we summarize the spectrum of toxicities, safety in special patients, rechallenging after irAEs and agents used for treatment of irAEs in those reports.
Adverse events induced by nivolumab and ipilimumab combination regimens. [2022]No meta-analysis has assessed the pooled frequencies of adverse events (AEs) induced by concomitant nivolumab plus ipilimumab regimen for anticancer-medications-naïve malignancies. Furthermore, no meta-analysis has compared detailed safety profiles between four doses of nivolumab 3 mg/kg plus ipilimumab 1 mg/kg every 3 weeks (N3I1) and four doses of nivolumab 1 mg/kg plus ipilimumab 3 mg/kg every 3 weeks (N1I3). Objectives of this study was estimating AE frequencies, and comparison of AE frequencies between N3I1 and N1I3 regimens.
Side effects of immune-checkpoint inhibitors: Can multiple side effects be seen in a patient? [2022]Nivolumab is a human immunoglobulin G4 monoclonal antibody that inhibits programmed cell death-1 activity by binding to the programmed cell death-1 receptors. Cancer cells express increased number of programmed cell death-1 ligands and this allows them to escape the cytotoxic effects of the T cells. Therefore, the negative programmed cell death-1 receptor signal regulates T-cell proliferation and activation is disrupted. However, this change in the activity of the T cells can cause them to lose their ability to recognize host cells. The immune response enabled by these agents has led to side effects, commonly known as "immune-related adverse events."
Adverse Events Induced by Nivolumab Plus Ipilimumab vs. Nivolumab Monotherapy among Cancer Patients: A Systematic Review and Meta-Analysis. [2022]A systematic review and meta-analysis of randomized controlled trials (RCTs) were performed to examine treatment-related adverse events (TRAEs) for combination of nivolumab (NIVO) and ipilimumab (IPI) compared to NIVO monotherapy among cancer patients. We searched several databases to identify relevant RCTs. Meta-analysis was performed using random-effects model. In fourteen RCTs included in the study, we found that compared to NIVO monotherapy, combination NIVO + IPI increased the risk of any grade (Risk Ratio (RR) = 1.11), and grade 3 or 4 (RR = 1.95) TRAEs. Compared to NIVO, NIVO + IPI had higher risk for any grade colitis (RR = 4.52), pneumonitis (RR = 3.06), and diarrhea (RR = 1.68).
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]Nivolumab is a human monoclonal antibody against programmed cell death receptor-1 (PD-1) able to rescue quiescent tumor infiltrating cytotoxic T lymphocytes (CTLs) restoring their ability to kill target cells expressing specific tumor antigen-derived epitope peptides bound to homologue human leukocyte antigen (HLA) molecules. Nivolumab is currently an active but expensive therapeutic agent for metastatic non-small cell lung cancer (mNSCLC), producing, in some cases, immune-related adverse events (irAEs). At the present, no reliable biomarkers have been validated to predict either treatment response or adverse events in treated patients.
An update on the pharmacodynamics, pharmacokinetics, safety and clinical efficacy of nivolumab in the treatment of solid cancers. [2018]Nivolumab is a programmed cell death 1 (PD-1) inhibitor that has been approved for treatment of advanced melanoma, non-small cell lung carcinoma, renal cell carcinoma and classical Hodgkin's lymphoma.
Nivolumab: a review of its use in patients with malignant melanoma. [2021]Nivolumab (Opdivo(®)) is a fully human monoclonal antibody against programmed death receptor-1, a negative regulatory checkpoint molecule with a role in immunosuppression. The drug is administered intravenously and is approved for the treatment of unresectable malignant melanoma in Japan. The potential for intravenous nivolumab to be used in the treatment of advanced malignancies such as melanoma was initially demonstrated in phase I dose-ranging trials. Subsequently, in a noncomparative, open-label, phase II trial, almost one-quarter of Japanese patients with previously treated stage III/IV melanoma (recurrent or unresectable) achieved a partial tumour response with intravenous nivolumab 2 mg/kg every 3 weeks. The clinical benefit of the drug was durable, with patients surviving free from progression for a median of 172 days and median overall survival not yet reached. Nivolumab had an acceptable tolerability profile in this trial, with fewer than 18 % of patients experiencing grade 3 or 4 adverse events related to the drug, the most common of which was increased γ-glutamyl transferase. Thus, nivolumab is an emerging, promising option for the treatment of malignant melanoma.