BT7480 + Nivolumab for Cancer

Recruiting at 8 trial locations

Overseen By Matthew Zibelman, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: BicycleTx Limited

Must not be taking: Immunotherapy, CD137 therapy

Disqualifiers: Brain metastases, Diabetes, Hypertension, others

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

Compensation: Varies

Number of Visits: Unknown

200 Participants Needed

Trial Summary

What is the purpose of this trial?

This clinical study is evaluating a drug called BT7480 alone and in combination with nivolumab in participants with advanced solid tumors associated with Nectin-4 expression. The main goals of the study are to: * Find the recommended dose of BT7480 that can be given safely to participants alone and in combination with nivolumab * Learn about the side effects and effectiveness of BT7480 alone and in combination with nivolumab * Learn about the effect BT7480 has on the body and how BT7480 is cleared by the body * Learn about the side effects and effectiveness of BT7480 in patients with reduced kidney function

Do I need to stop my current medications for the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot have had cytotoxic, small molecule, or other systemic chemotherapy within 14 days, or immunotherapy within 28 days or 5 half-lives of the first dose of the study drug. Please consult with the trial team for more details.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot have had certain cancer treatments like chemotherapy or immunotherapy shortly before starting the trial.

What data supports the idea that BT7480 + Nivolumab for Cancer is an effective drug?

The available research shows that Nivolumab, when used alone, has been effective in treating advanced non-small cell lung cancer (NSCLC). In the CheckMate 017 trial, patients treated with Nivolumab had better survival rates and fewer side effects compared to those treated with another drug, docetaxel. This suggests that Nivolumab is a promising option for cancer treatment. However, there is no specific data provided on the combination of BT7480 and Nivolumab, so we can't directly compare it to other treatments or confirm its effectiveness for other conditions. ^{1 2 3 4 5}

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

Nivolumab has shown significant effectiveness in improving overall survival and response rates in patients with advanced non-small cell lung cancer (NSCLC) compared to traditional chemotherapy, as demonstrated in clinical trials like CheckMate 017 and CheckMate 057. ^{1 2 3 4 5}

What safety data is available for BT7480 and Nivolumab in cancer treatment?

The provided research does not directly address the safety data for BT7480 combined with Nivolumab. However, it includes safety data for Nivolumab in combination with other treatments like Ipilimumab in various cancers such as metastatic NSCLC, melanoma, and colorectal cancer. These studies generally report a manageable safety profile for Nivolumab when used with Ipilimumab, with treatment-related adverse events being a consideration. No specific safety data for BT7480 is mentioned in the provided research. ^{6 7 8 9 10}

Is the combination of BT7480 and Nivolumab safe for humans?

Nivolumab, often used with other drugs like ipilimumab, has been studied in various cancers and generally shows a manageable safety profile, meaning side effects can be controlled. However, specific safety data for the combination of BT7480 and Nivolumab is not available in the provided research. ^{6 7 8 9 10}

Is the drug BT7480, Nivolumab (Opdivo) a promising treatment for cancer?

Yes, Nivolumab (Opdivo) is a promising drug for cancer treatment. It has shown significant improvements in survival rates and response in patients with advanced lung cancer, and it is well-tolerated compared to other treatments. This makes it an important advancement in cancer therapy. ^{1 2 3 11 12}

What makes the drug BT7480 + Nivolumab unique for cancer treatment?

BT7480 + Nivolumab is unique because it combines a novel treatment (BT7480) with Nivolumab, an immune checkpoint inhibitor that blocks PD-1, enhancing the body's immune response against cancer. This combination may offer a new approach for patients who have not responded to other treatments, especially since Nivolumab has shown effectiveness in various cancers by improving survival rates and being better tolerated than some traditional chemotherapy options. ^{1 2 3 11 12}

Eligibility Criteria

This trial is for adults with advanced solid tumors that express Nectin-4 and have not responded to standard treatments or have no suitable standard treatment options. Participants must be in relatively good health (ECOG score 0 or 1), have a life expectancy of at least 12 weeks, and provide tumor tissue samples.

Inclusion Criteria

My cancer is confirmed to be linked with Nectin-4 expression.

My advanced cancer does not respond to standard treatments.

Life expectancy ≥12 weeks

Exclusion Criteria

I have an autoimmune disease, but it's not diabetes, alopecia, thyroid disease, or vitiligo.

My diabetes is not under control, with an HbA1c level of 8% or higher.

I haven't had chemotherapy or similar treatments in the last 14 days.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase 1 Dose Escalation

Participants receive increasing doses of BT7480 to evaluate safety and tolerability as a monotherapy and in combination with nivolumab

6 months

Weekly visits

Phase 2 Dose Expansion

Participants receive a selected dose of BT7480 alone and in combination with nivolumab to assess clinical activity

6 months

Weekly visits

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 months

Treatment Details

Interventions

• BT7480
• Nivolumab

Trial Overview The study tests the drug BT7480 alone and combined with nivolumab to determine safe dosages, side effects, effectiveness, how it affects the body, and its clearance. It also examines BT7480's impact on patients with reduced kidney function.

Participant Groups

Group I: BT7480 monotherapy in patients with renal insufficiency Experimental Treatment 1 Intervention

Participants will receive a selected dose of BT7480. It is expected that approximately 12 patients will participate in this dose confirmation arm.

Group II: BT7480 monotherapy dose expansion Experimental Treatment 1 Intervention

Participants will receive a selected dose of BT7480. It is expected that approximately 45 patients will participate in this dose expansion arm in Phase 2.

Group III: BT7480 monotherapy dose escalation Experimental Treatment 1 Intervention

Participants will receive increasing doses of BT7480. It is expected that approximately 80 patients will participate in this dose escalation arm.

Group IV: BT7480 and nivolumab dose expansion Experimental Treatment 2 Interventions

Participants will receive a selected dose of BT7480 and standard dose of nivolumab. It is expected that approximately 45 patients will participate in this dose expansion arm in Phase 2.

Group V: BT7480 and nivolumab dose escalation Experimental Treatment 2 Interventions

Participants will receive increasing doses of BT7480 and standard dose of nivolumab. It is expected that approximately 12 patients will participate in this dose escalation arm.

Who Is Running the Clinical Trial?

BicycleTx Limited

Lead Sponsor

Trials

5

Recruited

1,800+

Findings from Research

Nivolumab, an immune checkpoint inhibitor, significantly improves overall survival and progression-free survival in patients with advanced stage squamous cell non-small cell lung cancer (NSCLC) compared to docetaxel, as shown in the CHECKMATE 017 study.

The safety and tolerability of nivolumab are favorable, and interestingly, the expression of the PD-L1 ligand does not predict treatment outcomes, suggesting that other factors may influence the effectiveness of this therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab in the treatment of metastatic squamous non-small cell lung cancer: a review of the evidence. Lim, JS., Soo, RA.[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, an anti-PD-1 antibody, was administered to a 63-year-old female patient with metastatic melanoma after renal transplantation, highlighting the potential for anti-tumor activity in high-risk patients, despite the challenges of concurrent immunosuppression.

The patient experienced acute renal allograft rejection and renal failure shortly after starting nivolumab, indicating significant risks associated with this treatment in transplant recipients, but she later showed a positive clinical response after re-challenging with nivolumab while on hemodialysis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antitumor activity of nivolumab on hemodialysis after renal allograft rejection. Ong, M., Ibrahim, AM., Bourassa-Blanchette, S., et al.[2023]

Nivolumab and pembrolizumab are FDA-approved monoclonal antibodies that target PD-1, helping to enhance T cell activity against cancer by blocking the PD-1/PD-L1 interaction, which allows cancer cells to escape immune detection.

Both drugs have shown efficacy across multiple cancer types, including melanoma and non-small cell lung cancer, and are considered interchangeable options for treating these conditions, which may help manage the rising costs of cancer therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab and pembrolizumab: Monoclonal antibodies against programmed cell death-1 (PD-1) that are interchangeable. Prasad, V., Kaestner, V.[2022]

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]

In a study of 1255 patients with metastatic non-small cell lung cancer (NSCLC), first-line treatment with nivolumab plus ipilimumab (NIVO+IPI) showed a high incidence of treatment-related adverse events (TRAEs), with 78% experiencing any-grade TRAEs and 34% experiencing severe (grade 3 or 4) TRAEs, but the treatment was generally well tolerated.

Patients who discontinued NIVO+IPI due to TRAEs still had a favorable long-term survival rate, with a 3-year overall survival of 50%, indicating that stopping treatment because of side effects did not negatively impact their long-term outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of First-Line Nivolumab Plus Ipilimumab in Patients With Metastatic NSCLC: A Pooled Analysis of CheckMate 227, CheckMate 568, and CheckMate 817. Paz-Ares, LG., Ciuleanu, TE., Pluzanski, A., et al.[2023]

The combination of ibrutinib and nivolumab demonstrated an acceptable safety profile in 141 patients with relapsed or refractory B-cell malignancies, with only one dose-limiting toxicity reported, indicating that this treatment approach is generally safe for patients.

Preliminary results showed promising efficacy, with overall response rates of 61% in high-risk chronic lymphocytic leukaemia, 33% in follicular lymphoma, and 36% in diffuse large B-cell lymphoma, suggesting that this combination therapy could be effective for these conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and activity of ibrutinib in combination with nivolumab in patients with relapsed non-Hodgkin lymphoma or chronic lymphocytic leukaemia: a phase 1/2a study. Younes, A., Brody, J., Carpio, C., et al.[2021]

In the CheckMate 142 study involving 119 patients with previously treated MSI-H/dMMR metastatic colorectal cancer, the combination of nivolumab and low-dose ipilimumab showed a high objective response rate (ORR) of 55% and a promising 12-month overall survival (OS) rate of 85%.

Most treatment-related adverse events (sTRAEs) were manageable, occurring early and resolving quickly, with comparable efficacy outcomes between patients with and without sTRAEs, indicating a favorable benefit-risk profile for this treatment regimen.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of Nivolumab plus Low-Dose Ipilimumab in Previously Treated Microsatellite Instability-High/Mismatch Repair-Deficient Metastatic Colorectal Cancer. Morse, MA., Overman, MJ., Hartman, L., et al.[2020]

In the Asian subpopulation with advanced non-small cell lung cancer (NSCLC) and PD-L1 expression ≥1%, patients treated with nivolumab plus ipilimumab showed significantly improved overall survival (OS) and progression-free survival (PFS) compared to those receiving chemotherapy, with a 3-year OS rate of 53% versus 37%.

The safety profile of nivolumab plus ipilimumab was manageable, with grade 3-4 treatment-related adverse events occurring in 40% of patients, similar to the 36% in the chemotherapy group, indicating no new safety concerns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First-line nivolumab + ipilimumab in advanced NSCLC: CheckMate 227 subpopulation analyses in Asian patients. O'Byrne, KJ., Lee, KH., Kim, SW., et al.[2022]

In a study of 45 patients with metastatic melanoma treated with the combination of nivolumab and ipilimumab, the disease control rate was 54% and the objective response rate was 29%, indicating moderate efficacy in a real-world setting.

The treatment had a high toxicity profile, with 88% of patients experiencing adverse events, and 44% discontinuing treatment due to these events, highlighting the need for careful monitoring and management of side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-world efficacy and toxicity of combined nivolumab and ipilimumab in patients with metastatic melanoma. Parakh, S., Randhawa, M., Nguyen, B., et al.[2019]

The bispecific antibody described in patent US2019161548 targets both PD-1 and CTLA-4, which are important immune checkpoints in cancer, and has been shown to enhance the activation and proliferation of CD8+ T cells and stimulate CD4+ T cells.

Clinical trials are currently underway to assess the safety and effectiveness of this bispecific antibody, with hopes that it may outperform the existing combination therapy of nivolumab and ipilimumab in cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bispecific anti-PD-1/CTLA-4 antibody for advanced solid tumors. Perez-Santos, M.[2021]

In a study of 552 non-small cell lung cancer (NSCLC) cases, PD-L1 and IDO-1 were found to be expressed in 16.9% and 42.6% of cases, respectively, and were associated with higher levels of tumor-infiltrating lymphocytes (TILs), suggesting their potential roles in immune evasion.

B7-H4 was less frequently expressed and did not show the same association with TILs, indicating that PD-L1 and IDO-1 may be more critical in the immune response to lung cancer, which could inform future treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Differential Expression and Significance of PD-L1, IDO-1, and B7-H4 in Human Lung Cancer. Schalper, KA., Carvajal-Hausdorf, D., McLaughlin, J., et al.[2021]

References

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

Nivolumab in the treatment of metastatic squamous non-small cell lung cancer: a review of the evidence. [2018]

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

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

3. England pubmed.ncbi.nlm.nih.gov

Antitumor activity of nivolumab on hemodialysis after renal allograft rejection. [2023]

4. United States pubmed.ncbi.nlm.nih.gov

Nivolumab and pembrolizumab: Monoclonal antibodies against programmed cell death-1 (PD-1) that are interchangeable. [2022]

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

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

6. United States pubmed.ncbi.nlm.nih.gov

Safety of First-Line Nivolumab Plus Ipilimumab in Patients With Metastatic NSCLC: A Pooled Analysis of CheckMate 227, CheckMate 568, and CheckMate 817. [2023]

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

Safety and activity of ibrutinib in combination with nivolumab in patients with relapsed non-Hodgkin lymphoma or chronic lymphocytic leukaemia: a phase 1/2a study. [2021]

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

Safety of Nivolumab plus Low-Dose Ipilimumab in Previously Treated Microsatellite Instability-High/Mismatch Repair-Deficient Metastatic Colorectal Cancer. [2020]

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

First-line nivolumab + ipilimumab in advanced NSCLC: CheckMate 227 subpopulation analyses in Asian patients. [2022]

10. Australia pubmed.ncbi.nlm.nih.gov

Real-world efficacy and toxicity of combined nivolumab and ipilimumab in patients with metastatic melanoma. [2019]

11. England pubmed.ncbi.nlm.nih.gov

Bispecific anti-PD-1/CTLA-4 antibody for advanced solid tumors. [2021]

12. United States pubmed.ncbi.nlm.nih.gov

Differential Expression and Significance of PD-L1, IDO-1, and B7-H4 in Human Lung Cancer. [2021]