IMC-F106C Combinations for Solid Cancers

Recruiting at 83 trial locations

Overseen By Immunocore Medical Information EU

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Immunocore Ltd

Must not be taking: Antibiotics, Vaccines

Disqualifiers: CNS metastasis, Lung disease, others

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

Compensation: Varies

Number of Visits: Unknown

727 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called brenetafusp (also known as IMC-F106C), designed to help the immune system attack certain solid cancers. Researchers aim to assess the safety and effectiveness of brenetafusp, either alone or combined with other treatments like chemotherapy or immune therapies. This trial might suit individuals with PRAME-positive cancer and an HLA-A2 marker, especially if standard treatments have not succeeded. As a Phase 1, Phase 2 trial, participants have the opportunity to be among the first to receive this new treatment and help evaluate its effectiveness in a smaller group.

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.

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

Research has shown that brenetafusp (IMC-F106C) is generally safe for humans. In earlier studies, this treatment effectively activated T cells, which then moved into tumors, aiding the immune system in fighting cancer cells. These studies also found that brenetafusp is well-tolerated, with no major safety issues.

For those considering brenetafusp with other treatments, it remains safe when combined with anti-PD(L)1 drugs like pembrolizumab. It is also well-tolerated when used with chemotherapy or targeted therapies.

Although the current trial is in its early stages, previous research suggests that brenetafusp is a promising and generally safe option for individuals with PRAME-positive cancers. Consulting a healthcare provider is advisable to determine if this trial might be suitable. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about brenetafusp because it offers a fresh approach to treating solid cancers. Unlike traditional therapies that often rely on standard chemotherapy or broad-spectrum immunotherapies, brenetafusp is designed to target specific proteins involved in cancer growth. This precision allows for a more tailored treatment, potentially leading to better outcomes with fewer side effects. Furthermore, the combination of brenetafusp with other agents like pembrolizumab or targeted therapies can enhance its effectiveness, offering hope for improved response rates in patients who might not benefit from current standard treatments.

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

Research has shown that brenetafusp, also known as IMC-F106C, may help treat solid cancers with the PRAME antigen. Studies have found that it activates T cells, which then move into tumors, a positive sign for fighting cancer. Patients using brenetafusp have experienced lasting benefits, including partial improvements in cancers like melanoma and ovarian cancer. In this trial, participants may receive brenetafusp alone or with other treatments. For example, one arm involves brenetafusp with anti-PD1 drugs, while other arms combine it with chemotherapy or targeted therapies. Brenetafusp remains effective and is generally well-tolerated across these combinations. These findings suggest that brenetafusp could be a promising treatment option for people with certain solid tumors. ^{1 2 3 4 6}

Who Is on the Research Team?

Shaad Abdullah, MD

Principal Investigator

Immunocore Ltd

Shaad Abdullah, MD, FACP

Principal Investigator

Immunocore Ltd

Are You a Good Fit for This Trial?

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.

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• anti-PD(L)1
• IMC-F106C

Trial Overview

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.

How Is the Trial Designed?

Group I: Brenetafusp and Targeted Therapy Experimental Treatment 3 Interventions

Participants receive brenetafusp and a selected targeted therapy. Receipt of kinase inhibitor is dependent on histology.

Group II: Brenetafusp and Multimodal Therapy Experimental Treatment 1 Intervention

Participants receive brenetafusp, biologics (eg, pembrolizumab, bevacizumab) IV infusions and chemotherapy IV infusions based on histology.

Group III: Brenetafusp and Chemotherapy Experimental Treatment 1 Intervention

Participants receive brenetafusp and chemotherapy. Choice of chemotherapy is dependent on cohort.

Group IV: Brenetafusp and Anti-PD(L)1 Agent Experimental Treatment 1 Intervention

Participants receive brenetafusp and pembrolizumab.

Group V: Brenetafusp Monotherapy Experimental Treatment 1 Intervention

Participants receive brenetafusp.

Who Is Running the Clinical Trial?

Immunocore Ltd

Lead Sponsor

Trials

17

Recruited

4,400+

Published Research Related to This Trial

Tebentafusp, a novel bispecific protein targeting the Gp-100 protein in uveal melanoma, has shown an overall survival benefit in a recent phase III trial for patients with untreated metastatic uveal melanoma.

Unlike traditional treatments for cutaneous melanoma, tebentafusp effectively creates an immune response against tumor cells by targeting a specific peptide presented by HLA*A0201, highlighting its unique mechanism of action in this rare cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gp-100 as a Novel Therapeutic Target in Uveal Melanoma. Martinez-Perez, D., Viñal, D., Solares, I., et al.[2021]

Immunotherapy has significantly improved cancer treatment, especially for certain liquid tumors and some solid tumors, but many solid tumors remain challenging due to their 'cold' immune environments.

The ImmTAC platform, particularly the tebentafusp (IMCgp100) molecule, shows promise in targeting these cold tumors by redirecting T cells to attack cancer cells, demonstrating clinical efficacy in difficult-to-treat cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Novel TCR-based biologics: mobilising T cells to warm 'cold' tumours. Lowe, KL., Cole, D., Kenefeck, R., et al.[2019]

Tebentafusp is a groundbreaking bispecific T cell engager that targets HLA-A*02:01-positive uveal melanoma cells, activating T cells to attack and destroy tumor cells, demonstrating its mechanism of action in cancer treatment.

In January 2022, tebentafusp became the first approved treatment for adults with unresectable or metastatic uveal melanoma in the USA, with ongoing regulatory reviews in other countries, highlighting its significance in melanoma therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tebentafusp: First Approval. Dhillon, S.[2023]

In a phase 1b trial involving 85 heavily pretreated patients with metastatic cutaneous melanoma, tebentafusp combined with durvalumab and/or tremelimumab showed a promising overall survival rate of 76% at one year, indicating potential efficacy for patients who had previously progressed on checkpoint inhibitors.

The combination therapy was well-tolerated, with no new safety concerns or treatment-related deaths reported, suggesting that tebentafusp can be safely administered alongside existing checkpoint inhibitors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tebentafusp in combination with durvalumab and/or tremelimumab in patients with metastatic cutaneous melanoma: a phase 1 study. Hamid, O., Hassel, JC., Shoushtari, AN., et al.[2023]

In a multicenter phase I/II trial involving 84 patients with advanced melanoma, tebentafusp demonstrated a 1-year overall survival rate of 65%, indicating its efficacy in treating both metastatic uveal and cutaneous melanoma.

Tebentafusp was well-tolerated and showed a mechanism of action that includes the induction of T-cell activity and changes in cytokine levels, suggesting it effectively redirects T cells to target tumor cells expressing the gp100 antigen.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tebentafusp, A TCR/Anti-CD3 Bispecific Fusion Protein Targeting gp100, Potently Activated Antitumor Immune Responses in Patients with Metastatic Melanoma. Middleton, MR., McAlpine, C., Woodcock, VK., et al.[2022]

Tebentafusp, approved by the FDA for treating unresectable or metastatic uveal melanoma, activates T cells to induce tumor cell death, showing a 1-year overall survival rate of 73% in Phase III trials with a disease control rate of 46%.

Common side effects include cytokine release syndrome and rash, but the drug's unique mechanism offers a promising alternative for patients with limited treatment options and poor prognosis in this specific type of melanoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tebentafusp: a novel drug for the treatment of metastatic uveal melanoma. Wang, Z., Xie, Y., Wang, JQ., et al.[2023]

Uveal melanoma, a rare and aggressive form of melanoma, has shown poor responses to traditional immune checkpoint inhibitors, highlighting the need for new treatment strategies.

Tebentafusp, a first-in-class bi-specific fusion protein therapy, has demonstrated a significant overall survival benefit in patients with uveal melanoma compared to standard treatment options, marking a promising advancement in this challenging cancer type.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Review of bi-specific therapies in uveal melanoma. Orloff, M., Seedor, R., Sato, T.[2023]

Citations

1.

ascopubs.org

ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.9507

Phase 1 safety and efficacy of IMC-F106C, a PRAME × ...

Dose escalation results showed robust T cell activation, T cell infiltration into tumor, and clinical activity in various solid tumors ( ...

2.

immunocore.com

immunocore.com/investors/news/press-releases/detail/92/immunocore-reports-updated-phase-1-data-of-brenetafusp-imc-f106c-an-immtac-bispecific-targeting-prame-in-immune-checkpoint-pre-treated-cutaneous-melanoma-patients-at-asco-2024

Immunocore reports updated Phase 1 data of brenetafusp ...

Brenetafusp was shown to be well tolerated, in monotherapy and in combination with anti-PD1, and demonstrated durable clinical benefit.

3.

jitc.bmj.com

jitc.bmj.com/content/12/Suppl_2/A796

694 Phase 1 safety and efficacy of brenetafusp, a PRAME ...

Brenetafusp, a PRAMExCD3 ImmTAC bispecific, showed robust T cell activation and infiltration into tumors and activity in various solid tumors.

4.

annalsofoncology.org

annalsofoncology.org/article/S0923-7534(22)02705-3/fulltext

728O Results from phase I dose escalation of IMC-F106C ...

IMC-F106C, the first PRAME×CD3 ImmTAC, is well tolerated and demonstrated durable RECIST partial responses and ctDNA response in PRAME+ pts across multiple ...

5.

dfhcc.harvard.edu

dfhcc.harvard.edu/fileadmin/media/ETCTN/06_NewsandAnnouncements/IMC-F106C_NSC_853198_Announcement_of_Availability.pdf

CTEP RAPID COMMUNICATION

Durable objective responses were demonstrated in patients with various solid tumors, including uveal melanoma, cutaneous melanoma (CM), and ...

6.

immunocore.com

immunocore.com/investors/news/press-releases/detail/99/immunocore-presents-phase-1-data-of-brenetafusp-an-immtac-bispecific-targeting-prame-in-patients-with-ovarian-cancer

Immunocore presents Phase 1 data of brenetafusp, an ...

Brenetafusp is clinically active as monotherapy and in combination with chemotherapy in heavily pre-treated, platinum-resistant ovarian cancer patients.