INCB 99280 + Ipilimumab for Solid Cancers

No longer 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment combination for certain solid cancers, including melanoma, liver, kidney, and colon cancers. The researchers aim to assess the safety and effectiveness of combining INCB 99280 (an experimental treatment) with ipilimumab for these cancers. Participants will receive varying doses to determine the most effective regimen. Suitable candidates have a diagnosis of one of these cancers, have not previously tried certain immune therapies, and maintain a good performance status (able to perform daily activities with minimal difficulty). As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

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.

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

Research is examining the safety and tolerability of combining INCB 99280 with ipilimumab. Ipilimumab, already FDA-approved for other cancers, can cause side effects like tiredness and skin rash but is generally well-tolerated.

This study is in its early stages, focusing on patient response to the treatment. This phase is crucial for identifying potential risks, though data remains limited. Researchers are closely monitoring the combination's safety in individuals with certain solid tumors. Participants receive two different doses of INCB 99280 along with ipilimumab to assess bodily responses.

This early phase primarily ensures the treatment's safety. The information gathered will help identify common side effects and their severity. While ipilimumab's safety is established from other treatments, INCB 99280 is still under investigation. Participants should consider this when deciding to join the trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of INCB 99280 and Ipilimumab for solid cancers because it offers a novel approach to treatment. Unlike traditional therapies, which often rely solely on immune checkpoint inhibitors or chemotherapy, INCB 99280 targets specific pathways that may enhance the immune system's ability to fight cancer. By combining it with Ipilimumab, a well-known immune checkpoint inhibitor, the treatment aims to boost the body's immune response more effectively against tumors like renal cell carcinoma (RCC), microsatellite instability-high (MSI-H)/mismatch repair deficient (dMMR) colorectal cancer (CRC), melanoma, and hepatocellular carcinoma (HCC). This dual-action strategy could potentially improve outcomes for patients who have limited options with existing therapies.

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

Research shows that ipilimumab can help people with advanced melanoma live longer by strengthening the immune system, enabling the body to fight cancer cells more effectively. In this trial, participants will receive a combination of ipilimumab and INCB 99280. Researchers are studying INCB 99280 to assess its safety and effectiveness when combined with ipilimumab. Although limited information exists about INCB 99280 in humans, researchers hope it will enhance treatment for certain solid tumors, such as melanoma, kidney cancer (renal cell carcinoma), and liver cancer (hepatocellular carcinoma). Early studies focus on understanding how this combination might improve patients' ability to combat these cancers. ^{1 2 3 4 6}

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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 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]

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 (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]

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]

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 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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05909995

NCT05909995 | Interventional Study of INCB 99280 With ... The purpose of this study is to characterize the safety, tolerability, PK, and efficacy of INCB 99280 in combination with ipilimumab in participants with ...

2. clinicaltrials.eu clinicaltrials.eu/trial/study-of-incb099280-and-ipilimumab-for-patients-with-advanced-solid-tumors/

Study of INCB099280 and Ipilimumab for Patients with ... This study examines the safety and tolerability of INCB099280 and Ipilimumab in patients with advanced solid tumors.

3. withpower.com withpower.com/trial/phase-1-hepatocellular-carcinoma-6-2023-07f3f

INCB 99280 + 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 ...

4. careacross.com careacross.com/clinical-trials/trial/NCT05909995

Interventional Study of INCB 99280 With Ipilimumab in ... Summary: The purpose of this study is to characterize the safety, tolerability, PK, and efficacy of INCB 99280 in combination with ipilimumab in participants ...

5. aging.networkofcare.org aging.networkofcare.org/sanmateo/CommunityResources/ClinicalTrials/Detail/NCT05909995?keyword=%22RCC%22

Interventional Study of INCB 99280 With Ipilimumab in ... The purpose of this study is to characterize the safety, tolerability, PK, and efficacy of INCB 99280 in combination with ipilimumab in participants with ...

6. ctv.veeva.com ctv.veeva.com/study/interventional-study-of-incb-99280-with-ipilimumab-in-participants-with-select-solid-tumors

Interventional Study of INCB 99280 With Ipilimumab in ... The purpose of this study is to characterize the safety, tolerability, PK, and efficacy of INCB 99280 in combination with ipilimumab in ...