IMC-F106C Combinations for Solid Cancers
Recruiting in Palo Alto (17 mi)
+82 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 1 & 2
Recruiting
Sponsor: Immunocore Ltd
Must not be taking: Antibiotics, Vaccines
Disqualifiers: CNS metastasis, Lung disease, others
No Placebo Group
Breakthrough Therapy
Trial Summary
What is the purpose of this trial?This trial tests IMC-F106C, a treatment that helps the immune system target and kill cancer cells in adults with advanced cancers. It guides immune cells to attack cancer cells more effectively.
Will I have to stop taking my current medications?
The trial does not specify if you must stop taking your current medications, but it mentions that there should be an adequate washout period (time without taking certain medications) from prior anticancer therapy. It's best to discuss your current medications with the trial team.
What data supports the effectiveness of the treatment IMC-F106C Combinations for Solid Cancers?
Tebentafusp, a similar treatment, has shown effectiveness in treating metastatic uveal melanoma by improving overall survival rates, even though the response rate was modest. This suggests that combining immune therapies, like those in the IMC-F106C trial, could potentially enhance treatment outcomes for solid cancers.
12345What makes the drug IMC-F106C unique for treating solid cancers?
IMC-F106C, also known as Brenetafusp, is a novel treatment that uses a bispecific T cell engager approach to target cancer cells by redirecting T cells to attack them, which is different from traditional therapies that may not effectively engage the immune system in 'cold' tumors (tumors that are not easily recognized by the immune system). This approach is particularly promising for solid tumors that have been difficult to treat with existing therapies.
12367Eligibility Criteria
This trial is for adults with solid tumors that have relapsed, are resistant to standard therapy, or can't tolerate it. Participants must test positive for HLA-A*02:01 and PRAME in their tumors and agree to use effective contraception if applicable. They should be able to consent and follow the study's rules but can't join if they have serious heart, lung, autoimmune diseases, transplants, active hepatitis B/C, HIV, significant other cancers or allergies related to the study drugs.Inclusion Criteria
If applicable, must agree to use highly effective contraception
I am fully active or restricted in physically strenuous activity but can do light work.
I am HLA-A*02:01 positive.
+3 more
Exclusion Criteria
I had a severe reaction to previous immunotherapy.
I have an active hepatitis B or C infection.
I recently had cancer treatment and haven't waited long enough to start a new one.
+14 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Phase 1: Dose Escalation
To identify the Maximum Tolerated Dose (MTD) and/or Recommended Phase 2 dose (RP2D) of brenetafusp as a single agent and in combination with other therapies
12-24 weeks
Phase 2: Efficacy Assessment
To assess the efficacy of brenetafusp in selected advanced solid tumors
24-48 weeks
Follow-up
Participants are monitored for safety and effectiveness after treatment
12 weeks
Participant Groups
The trial tests IMC-F106C alone and combined with cancer treatments like atezolizumab (a checkpoint inhibitor), pembrolizumab (another checkpoint inhibitor), chemotherapy or tebentafusp. It aims to see how safe and effective these combinations are against cancers that show a specific antigen called PRAME.
5Treatment groups
Experimental Treatment
Group I: Brenetafusp and Targeted TherapyExperimental Treatment3 Interventions
Participants receive brenetafusp and a selected targeted therapy. Receipt of kinase inhibitor is dependent on histology.
Group II: Brenetafusp and Multimodal TherapyExperimental Treatment1 Intervention
Participants receive brenetafusp, biologics (eg, pembrolizumab, bevacizumab) IV infusions and chemotherapy IV infusions based on histology.
Group III: Brenetafusp and ChemotherapyExperimental Treatment1 Intervention
Participants receive brenetafusp and chemotherapy. Choice of chemotherapy is dependent on cohort.
Group IV: Brenetafusp and Anti-PD(L)1 AgentExperimental Treatment1 Intervention
Participants receive brenetafusp and pembrolizumab.
Group V: Brenetafusp MonotherapyExperimental Treatment1 Intervention
Participants receive brenetafusp.
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
CHUM Centre de RechercheMontréal, Canada
Georgetown University Medical CenterWashington, United States
Princess Margaret Cancer CentreToronto, Canada
Winship Cancer Institute of Emory universityAtlanta, GA
More Trial Locations
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Who Is Running the Clinical Trial?
Immunocore LtdLead Sponsor
References
Tebentafusp in combination with durvalumab and/or tremelimumab in patients with metastatic cutaneous melanoma: a phase 1 study. [2023]Immune checkpoint inhibitors have significantly improved outcomes in first line cutaneous melanoma. However, there is a high unmet need for patients who progress on these therapies and combination therapies are being explored to improve outcomes. Tebentafusp is a first-in-class gp100×CD3 ImmTAC bispecific that demonstrated overall survival (OS) benefit (HR 0.51) in metastatic uveal melanoma despite a modest overall response rate of 9%. This phase 1b trial evaluated the safety and initial efficacy of tebentafusp in combination with durvalumab (anti-programmed death ligand 1 (PDL1)) and/or tremelimumab (anti-cytotoxic T lymphocyte-associated antigen 4) in patients with metastatic cutaneous melanoma (mCM), the majority of whom progressed on prior checkpoint inhibitors.
Tebentafusp: a novel drug for the treatment of metastatic uveal melanoma. [2023]On January 25, 2022, the U.S. Food and Drug Administration (FDA) approved the use of tebentafusp, a bispecific glycoprotein 100 (gp100) peptide-human leukocyte antigen (HLA)-directed CD3 T-cell activator, for the treatment of HLA-A*02:01-positive adult patients with unresectable or metastatic uveal melanoma (mUM). Pharmacodynamic data indicate that tebentafusp targets a specific HLA-A*02:01/gp100 complex, activating both CD4+/CD8+ effector and memory T cells that induce tumor cell death. Tebentafusp is administered to patients via intravenous infusion daily or weekly, depending on the indication. Phase III trials have documented a 1-year overall survival of 73%, overall response rate of 9%, progression-free survival of 31% and disease control rate of 46%. Common adverse events reported are cytokine release syndrome, rash, pyrexia, pruritus, fatigue, nausea, chills, abdominal pain, edema, hypotension, dry skin, headache and vomiting. Compared to other types of melanomas, mUM presents with a distinct profile of genetic mutations, which phenotypically results in limited survival efficacy when using traditional melanoma treatments. The low current treatment efficacy for mUM, alongside a poor long-term prognosis and high mortality rates, gives precedence for the approval of tebentafusp to be groundbreaking in its clinical impact. This review will discuss the pharmacodynamic and pharmacokinetic profile, and the clinical trials used to evaluate the safety and efficacy of tebentafusp.
Tebentafusp: First Approval. [2023]Tebentafusp (tebentafusp-tebn; Kimmtrak®) is a first-in-class, bispecific gp100 peptide-HLA-A*02:01 directed T cell receptor (TCR) CD3 T cell engager being developed by Immunocore for the treatment of uveal melanoma and malignant melanoma. The TCR arm of tebentafusp binds to HLA-A*02:01-positive uveal melanoma cells and activates polyclonal T cells, through CD3, to release inflammatory cytokines and cytolytic proteins, resulting in the direct lysis of tumour cells. In January 2022, tebentafusp received its first approval in the USA for the treatment of HLA-A*02:01-positive adults with unresectable or metastatic uveal melanoma, and in February 2022 received a Positive Opinion from the EU Committee for Medicinal Products for Human Use for the treatment of uveal melanoma. Tebentafusp is under regulatory review for the treatment of metastatic uveal melanoma in the UK, Australia and Canada. Clinical studies of tebentafusp are underway for uveal melanoma and cutaneous melanoma in several countries worldwide. This article summarizes the milestones in the development of tebentafusp leading to this first approval for unresectable or metastatic uveal melanoma.
Gp-100 as a Novel Therapeutic Target in Uveal Melanoma. [2021]Uveal melanoma is a rare neoplasm with poor prognosis in the metastatic setting. Unlike cutaneous melanoma, treatment with kinase inhibitors or immune checkpoint inhibitors is not effective. Glycoprotein 100 (Gp-100) is a protein highly expressed in melanocytes and melanoma that has recently been effectively targeted by tebentafusp, a first-in-class bispecific protein of the immune-mobilizing monoclonal T cell receptors against cancer (ImmTACs) family. Tebentafusp targets tumor cells that express a peptide of Gp-100 presented by HLA*A0201, creating an immune synapse that kills targeted tumor cells. Recently, a randomized phase III trial reported an overall survival benefit for tebentafusp in patients with untreated metastatic uveal melanoma. The aim of this comprehensive review is to summarize evidence of Gp-100 as a therapeutic target in melanoma, and the preclinical and clinical development of tebentafusp as a novel therapeutic strategy for patients with uveal melanoma.
Tebentafusp, A TCR/Anti-CD3 Bispecific Fusion Protein Targeting gp100, Potently Activated Antitumor Immune Responses in Patients with Metastatic Melanoma. [2022]Tebentafusp is a first-in-class bispecific fusion protein designed to target gp100 (a melanoma-associated antigen) through a high affinity T-cell receptor (TCR) binding domain and an anti-CD3 T-cell engaging domain, which redirects T cells to kill gp100-expressing tumor cells. Here, we report a multicenter phase I/II trial of tebentafusp in metastatic melanoma (NCT01211262) focusing on the mechanism of action of tebentafusp.
Novel TCR-based biologics: mobilising T cells to warm 'cold' tumours. [2019]Immunotherapeutic strategies have revolutionised cancer therapy in recent years, bringing meaningful improvements in outcomes for patients with previously intractable conditions. These successes have, however, been largely limited to certain types of liquid tumours and a small subset of solid tumours that are known to be particularly immunogenic. Broadening these advances across the majority of tumour indications, which are characterised by an immune-excluded, immune-deserted or immune-suppressed ('cold') phenotype, will require alternative approaches that are able to specifically address this unique biological environment. Several newer therapeutic modalities, including adoptive cell therapy and T cell redirecting bispecific molecules, are considered to hold particular promise and are being investigated in early phase clinical trials across various solid tumour indications. ImmTAC molecules are a novel class of T cell redirecting bispecific biologics that exploit TCR-based targeting of tumour cells; providing potent and highly specific access to the vast landscape of intracellular targets. The first of these reagents to reach the clinic, tebentafusp (IMCgp100), has generated demonstrable clinical efficacy in an immunologically cold solid tumour with a high unmet need. Here, we highlight the key elements of the ImmTAC platform that make it ideally positioned to overcome the cold tumour microenvironment in an off-the-shelf format.
Review of bi-specific therapies in uveal melanoma. [2023]Uveal melanoma is a rare subtype of melanoma that once metastatic portends a poor prognosis. Likely due to the distinct differences in biology, metastatic potential, and immunologic profile as compared to cutaneous melanoma, uveal melanoma's response to immune checkpoint inhibition has been disappointing. Bi-specific fusion protein therapies (T cell engagers) are a novel strategy to forcibly bridge the immune system with a target on a cancer cell. This approach has been explored in a number of cancer types and has recently demonstrated success in uveal melanoma. Tebentafusp, a first in class ImmTAC (Immune-mobilizing monoclonal TCRs against cancer), has now shown an overall survival benefit when compared to investigator's choice. This review aims to summarize the experience with this first in class bi-specific T cell engager as well as highlight bi-specifics as a novel treatment strategy in uveal melanoma.