INCB 99280 + Ipilimumab for Solid Cancers

Recruiting at 59 trial locations

Overseen By Incyte Corporation Call Center (ex-US)

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Incyte Corporation

Must not be taking: Systemic steroids, Systemic antibiotics

Disqualifiers: Additional malignancy, CNS metastases, others

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

Compensation: Varies

Number of Visits: Unknown

8 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing a new drug called INCB 99280 along with an existing cancer treatment, ipilimumab. Ipilimumab is a treatment that has been approved for use in advanced melanoma and is being studied for other types of solid tumors. The goal is to see if this combination can help the immune system fight cancer more effectively.

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

The trial protocol does not specify if you need to stop taking your current medications. However, certain conditions like active infections requiring systemic therapy or recent use of systemic antibiotics may affect eligibility.

What data supports the effectiveness of the drug combination INCB 99280 and Ipilimumab for solid cancers?

Ipilimumab, a part of the treatment, has been shown to improve survival in patients with advanced melanoma by enhancing the body's immune response against cancer cells. It has been approved for use in melanoma and is being studied for other cancers, suggesting potential effectiveness in solid tumors. ^{1 2 3 4 5}

Is the combination of INCB 99280 and Ipilimumab safe for humans?

Ipilimumab, also known as Yervoy, has been used in treating melanoma and other cancers, but it can cause significant immune-related side effects, such as inflammation of the pituitary gland (hypophysitis). When combined with other treatments like PD-1 inhibitors, it can lead to more frequent and severe side effects, which are often manageable with medications like glucocorticoids. Close monitoring by experienced healthcare providers is essential to manage these side effects effectively. ^{1 2 6 7 8}

How is the drug INCB 99280 + Ipilimumab different from other cancer treatments?

The combination of INCB 99280 and Ipilimumab is unique because it involves an immune checkpoint blockade (ICB) therapy, which enhances the body's immune response against cancer cells by blocking inhibitory signals. Ipilimumab specifically targets CTLA-4, a protein that downregulates immune responses, potentially leading to a stronger attack on tumor cells compared to traditional therapies. ^{1 2 9 10 11}

Eligibility Criteria

This trial is for adults with certain solid tumors like colorectal cancer, melanoma, and kidney cancer. Participants need a confirmed diagnosis with measurable disease, an ECOG score of 0 or 1 (which means they are fully active or restricted in physically strenuous activity but can do light work), and a life expectancy over three months. They must not be at risk of pregnancy or fathering children.

Inclusion Criteria

I meet the specific treatment and diagnosis criteria for the trial phase I'm entering.

My solid tumor can be measured and has been confirmed by a biopsy.

Exception Criterion: Hepatocellular carcinoma (liver cancer) may be diagnosed using specific imaging criteria.

Exclusion Criteria

I have an immune system disorder or take more than 10 mg of steroids daily.

I had chest radiation therapy within the last 6 months.

I am not in another clinical trial while taking INCB099280.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Participants with RCC and MSI-H/dMMR CRC receive INCB099280 BID with up to 4 doses of ipilimumab 1 mg/kg Q3 weeks; Participants with Melanoma and HCC receive INCB099280 BID with up to 4 doses of ipilimumab 3 mg/kg Q3 weeks

12 weeks

Dose Expansion

Participants with RCC and HCC receive INCB099280 BID with up to 4 doses of ipilimumab Q3 weeks

12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 years

Treatment Details

Interventions

• INCB 99280
• Ipilimumab

Trial Overview The study tests the combination of INCB 99280 with Ipilimumab to evaluate safety, how well it's tolerated by patients, its pharmacokinetics (how the body processes it), and effectiveness against select solid tumors. The trial has two parts: dose escalation to find the right dose and then dose expansion to test that dose more broadly.

Participant Groups

Group I: Dose Expansion Experimental Treatment 1 Intervention

* Participants with RCC will receive 1 of two doses of INCB099280 BID with up to 4 doses of ipilimumab 1 mg/kg Q3 weeks of ipilimumab * Participants with HCC will receive 1 of two doses of INCB099280 BID with up to 4 doses of ipilimumab 3 mg/kg Q3 weeks of ipilimumab

Group II: Dose Escalation Experimental Treatment 1 Intervention

* Participants with RCC and MSI-H/dMMR CRC will receive 1 of two doses of INCB099280 BID with up to 4 doses of ipilimumab 1 mg/kg Q3 weeks * Participants with Melanoma and HCC will receive 1 of 2 doses of INCB099280 BID with up to 4 doses of 3 ipilimumab 3 mg/kg Q3 weeks

Who Is Running the Clinical Trial?

Incyte Corporation

Lead Sponsor

Trials

408

Recruited

66,800+

Steven Stein

Incyte Corporation

Chief Medical Officer since 2015

MD from University of Witwatersrand

Hervé Hoppenot

Incyte Corporation

Chief Executive Officer since 2014

MBA from ESSEC Business School

Findings from Research

Ipilimumab (Yervoy®) is an approved monoclonal antibody for treating malignant melanoma by blocking the CTLA-4 protein, which enhances T-cell responses against tumor cells, showing its efficacy in cancer immunotherapy.

Currently, ipilimumab is also being tested in phase III trials for prostate cancer and phase II trials for non-small cell lung cancer, indicating its potential for broader applications in cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ipilimumab: first global approval. Cameron, F., Whiteside, G., Perry, C.[2021]

Ipilimumab, a monoclonal antibody used to enhance anti-tumor T-cell responses, can cause significant side effects, including ipilimumab-induced hypophysitis (IH), which affects hormone levels and requires hormone replacement therapy in most cases.

In a review of 10 patients with IH, early detection and management guidelines were developed, highlighting the importance of monitoring hormone levels and recognizing imaging abnormalities, which often resolve without high-dose glucocorticoid therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ipilimumab-induced hypophysitis in melanoma patients: an Australian case series. Lam, T., Chan, MM., Sweeting, AN., et al.[2022]

Ipilimumab (Yervoy), a CTLA-4 blocking antibody, has been FDA-approved and shown to significantly extend survival in patients with metastatic melanoma, a cancer that has seen little progress in treatment for over 40 years.

The review discusses the mechanism of CTLA-4, which normally inhibits T-cell activation, and highlights the promising results from recent clinical trials demonstrating the efficacy of CTLA-4 blockade in advanced melanoma, marking a significant advancement in cancer immunotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ipilimumab and cancer immunotherapy: a new hope for advanced stage melanoma. Mansh, M.[2023]

In a phase 2 trial involving 142 patients with untreated advanced melanoma, the combination of nivolumab and ipilimumab resulted in a 2-year overall survival rate of 63.8%, compared to 53.6% for those receiving ipilimumab alone, suggesting improved survival outcomes with the combination therapy.

However, the combination treatment was associated with a higher incidence of severe side effects, with 54% of patients experiencing grade 3-4 adverse events compared to 20% in the ipilimumab-only group, indicating a trade-off between efficacy and safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combined nivolumab and ipilimumab versus ipilimumab alone in patients with advanced melanoma: 2-year overall survival outcomes in a multicentre, randomised, controlled, phase 2 trial. Hodi, FS., Chesney, J., Pavlick, AC., et al.[2022]

Ipilimumab is a monoclonal antibody that enhances T cell activation by blocking the CTLA-4 receptor, leading to improved antitumor responses and has been shown to increase overall survival in patients with advanced melanoma, a condition with a poor prognosis.

While ipilimumab has demonstrated significant efficacy, it can cause serious immune-related adverse effects that require prompt management, highlighting the importance of monitoring patients during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ipilimumab: a novel immunostimulatory monoclonal antibody for the treatment of cancer. Graziani, G., Tentori, L., Navarra, P.[2020]

Combined immune checkpoint blockade (ICB) using nivolumab and ipilimumab shows significant efficacy in treating advanced melanoma, but it also leads to a higher frequency and severity of adverse drug reactions (ADRs) compared to single-agent therapies, based on pooled safety data from 1551 patients.

Most immune-related ADRs are reversible with glucocorticoids, but due to the increased risk and rapid onset of these toxicities, clinicians must be well-trained to monitor and manage these side effects effectively.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combined immune checkpoint blockade (anti-PD-1/anti-CTLA-4): Evaluation and management of adverse drug reactions. Hassel, JC., Heinzerling, L., Aberle, J., et al.[2022]

Ipilimumab is a monoclonal antibody that blocks CTLA-4, enhancing T-cell activation and leading to significant antitumor immune responses, which has been shown to improve survival in patients with advanced melanoma in two global phase 3 clinical studies involving over 13,000 patients.

Approved in over 40 countries, including the U.S. and EU, ipilimumab is the first treatment to demonstrate an overall survival benefit for advanced melanoma, with ongoing trials exploring its efficacy in other cancers like lung and gastric cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Ipilimumab]. Tokudome, T.[2017]

Ipilimumab is a pioneering immune checkpoint inhibitor that enhances the anti-tumor response of T cells by blocking CTLA-4, which is crucial for its mechanism of action against cancer.

Combining ipilimumab with anti-PD-1 antibodies has shown clinical benefits in treating advanced melanoma and renal cell cancer, indicating improved efficacy in these malignancies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Clinical Significance of Ipilimumab and the Combination Therapy as Immune Checkpoint Inhibitor]. Muto, Y., Kitano, S.[2019]

Immune checkpoint blockade (ICB) has revolutionized cancer treatment, showing significant effectiveness in metastatic melanoma and expanding to other cancer types and earlier stages.

The review discusses the mechanisms behind varying patient responses to ICB and its integration into both adjuvant (post-surgery) and neoadjuvant (pre-surgery) treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Eradicating micrometastases with immune checkpoint blockade: Strike while the iron is hot. Janjigian, YY., Wolchok, JD., Ariyan, CE.[2021]

Immune checkpoint blockers (ICBs) are transforming cancer treatment by targeting various co-inhibitory T-cell receptors, not just the well-known CTLA4 and PD-1, which opens up new possibilities for therapy.

There is a strong focus on identifying biomarkers that can predict which patients will benefit from ICBs, aiming to personalize treatment and minimize severe side effects, which is a key goal in the future of cancer immunotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trial watch: Immune checkpoint blockers for cancer therapy. Vanpouille-Box, C., Lhuillier, C., Bezu, L., et al.[2021]

Immune checkpoint blockade (ICB) therapy is effective for treating various tumors by enhancing T-cell activation, but its efficacy is limited in cold tumors due to an immunosuppressive tumor microenvironment.

Recent advances in nano-sized drug delivery systems (Nano-DDS) can enhance ICB therapy by converting cold tumors into immunogenic hot tumors, potentially improving patient responses through the combination of immunogenic cell death inducers and immune modulators.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nano-sized drug delivery systems to potentiate the immune checkpoint blockade therapy. Shim, MK., Song, SK., Jeon, SI., et al.[2022]

References

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

Ipilimumab: first global approval. [2021]

2. Australia pubmed.ncbi.nlm.nih.gov

Ipilimumab-induced hypophysitis in melanoma patients: an Australian case series. [2022]

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

Ipilimumab and cancer immunotherapy: a new hope for advanced stage melanoma. [2023]

4. England pubmed.ncbi.nlm.nih.gov

Combined nivolumab and ipilimumab versus ipilimumab alone in patients with advanced melanoma: 2-year overall survival outcomes in a multicentre, randomised, controlled, phase 2 trial. [2022]

5. Netherlands pubmed.ncbi.nlm.nih.gov

Ipilimumab: a novel immunostimulatory monoclonal antibody for the treatment of cancer. [2020]

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

Combined immune checkpoint blockade (anti-PD-1/anti-CTLA-4): Evaluation and management of adverse drug reactions. [2022]

7. Japan pubmed.ncbi.nlm.nih.gov

[Ipilimumab]. [2017]

8. Japan pubmed.ncbi.nlm.nih.gov

[Clinical Significance of Ipilimumab and the Combination Therapy as Immune Checkpoint Inhibitor]. [2019]

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

Eradicating micrometastases with immune checkpoint blockade: Strike while the iron is hot. [2021]

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

Trial watch: Immune checkpoint blockers for cancer therapy. [2021]

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

Nano-sized drug delivery systems to potentiate the immune checkpoint blockade therapy. [2022]