IMC-F106C Combinations for Solid Cancers

Recruiting at 82 trial 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. ^{1 2 3 4 5}

What 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. ^{1 2 3 6 7}

Research Team

Shaad Abdullah, MD

Principal Investigator

Immunocore Ltd

Shaad Abdullah, MD, FACP

Principal Investigator

Immunocore Ltd

Eligibility 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.

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.

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

Treatment Details

Interventions

• anti-PD(L)1 (Checkpoint Inhibitor)
• IMC-F106C (Monoclonal Antibodies)

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

Tebentafusp in combination with durvalumab and/or tremelimumab in patients with metastatic cutaneous melanoma: a phase 1 study. [2023]

2. Spain pubmed.ncbi.nlm.nih.gov

Tebentafusp: a novel drug for the treatment of metastatic uveal melanoma. [2023]

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

Tebentafusp: First Approval. [2023]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Gp-100 as a Novel Therapeutic Target in Uveal Melanoma. [2021]

5. United States 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. [2022]

6. Netherlands pubmed.ncbi.nlm.nih.gov

Novel TCR-based biologics: mobilising T cells to warm 'cold' tumours. [2019]

7. England pubmed.ncbi.nlm.nih.gov

Review of bi-specific therapies in uveal melanoma. [2023]