What is the mechanism of action of this treatment?

Common treatments for gastrointestinal cancers, particularly those involving immunotherapy, include immune checkpoint inhibitors and chimeric antigen receptor (CAR) T-cell therapies. Immune checkpoint inhibitors, such as anti-PD-1 and anti-CTLA-4 antibodies, work by blocking proteins that prevent T-cells from attacking cancer cells, thereby enhancing the immune response against tumors. CAR T-cell therapies involve modifying a patient's T-cells to express receptors that specifically target cancer cells. These treatments are significant for gastrointestinal cancer patients as they offer a targeted approach to boost the body's immune system to fight cancer, potentially leading to better outcomes and fewer side effects compared to traditional therapies.

What side effects are associated with this type of intervention?

Common treatments for gastrointestinal cancers, particularly those involving immunotherapy targeting CD8 T-cell-positive tumors, include agents like pembrolizumab and avelumab. Known side effects of these immunotherapies can include fatigue, diarrhea, rash, pruritus, and pneumonitis. Severe adverse events, although less common, may include severe skin reactions, hypomagnesemia, and infusion-related reactions. These treatments aim to harness the body's immune system to target cancer cells but can also lead to immune-related adverse effects due to increased immune activity.

What prior FDA approvals exist?

The FDA has approved several immunotherapies for the treatment of gastrointestinal cancers, particularly those targeting CD8 T-cell-positive tumors. Notable approvals include pembrolizumab (Keytruda) and nivolumab (Opdivo), both of which are immune checkpoint inhibitors targeting the PD-1/PD-L1 pathway. These drugs have shown efficacy in various gastrointestinal malignancies, including advanced gastric and colorectal cancers. Additionally, combination therapies such as nivolumab with ipilimumab (Yervoy) have been approved for certain gastrointestinal cancers, enhancing the immune response against tumor cells.

What other types of research exist?

Promising novel alternatives to INCA00186 for gastrointestinal cancer patients include: 1) Pembrolizumab (Keytruda), an anti-PD-1 therapy, which has shown efficacy in various gastrointestinal cancers. 2) Nivolumab (Opdivo), another anti-PD-1 therapy, often used in combination with other agents. 3) Atezolizumab (Tecentriq), an anti-PD-L1 therapy, which has been effective in certain gastrointestinal cancers. 4) Combination therapies such as Nivolumab with Ipilimumab (Yervoy), which target both PD-1 and CTLA-4 pathways. 5) Emerging therapies like CAR-T cell treatments and bispecific antibodies targeting specific tumor antigens.

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INCA 0186 Combination Therapy for Cancer

Phase 1

Waitlist Available

Research Sponsored by Incyte Corporation

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

ECOG performance status 0 or 1.

Participants with specified GI malignancies: Histologically or cytologically confirmed advanced or metastatic colorectal (CRC), gastric/gastroesophageal junction (GEJ) cancer, hepatocellular carcinoma (HCC), pancreatic ductal adenocarcinoma (PDAC), or squamous carcinoma of the anal canal (SCAC).

Must not have

Evidence of interstitial lung disease, history of interstitial lung disease, or active noninfectious pneumonitis

Known history of HIV (HIV 1/2 antibodies)

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 5 years

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing a new drug called INCA00186, alone or with other drugs, in patients with advanced head and neck or gastrointestinal cancers that have CD8 T-cells. The treatment uses immunotherapy to help the immune system attack cancer cells.

Who is the study for?

Adults over 18 with advanced solid tumors, specifically squamous cell carcinoma of the head and neck or certain gastrointestinal cancers. Participants must have CD8 T-cell-positive tumors, an ECOG performance status of 0 or 1, measurable disease, and be willing to undergo biopsies. They should have progressed after standard treatments including anti-PD-(L)1 therapy unless intolerant.

What is being tested?

The trial is testing INCA00186 alone or combined with INCB106385 and/or retifanlimab in patients with specific advanced solid tumors. It's a Phase 1 study focusing on safety, tolerability, how the body processes the drugs (pharmacokinetics), their effects on the body (pharmacodynamics), and initial effectiveness.

What are the potential side effects?

Potential side effects may include typical reactions related to immunotherapy such as inflammation in various organs, infusion-related reactions like fever or chills, fatigue, digestive issues like nausea or diarrhea, changes in blood counts leading to increased infection risk or bleeding tendencies.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I am fully active or can carry out light work.

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My cancer is advanced and confirmed in the GI area, such as colorectal, stomach, liver, pancreas, or anal canal.

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I have squamous cell carcinoma in my mouth or throat that cannot be cured with surgery or radiation.

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My cancer is advanced and confirmed in the GI area, such as colorectal, stomach, liver, pancreas, or anal canal.

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I am fully active or can carry out light work.

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My tumor is CD8 T-cell positive.

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I am willing to have tumor biopsies before and during treatment.

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I have squamous cell carcinoma in my mouth or throat that cannot be cured with surgery or radiation.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I have or had lung scarring or inflammation not caused by an infection.

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I have been diagnosed with HIV.

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I have not taken drugs targeting the adenosine pathway before.

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I have had an organ transplant or received CAR-T cell therapy.

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I have not received a live virus vaccine in the last 30 days.

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I have not needed IV drugs for an infection in the last week.

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I do not have serious heart problems or recent heart attacks.

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I have an immune system disorder or have been on high-dose steroids or other immune-weakening medicines recently.

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I haven't had cancer treatment within the last 28 days or 5 half-lives, whichever is shorter.

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I currently have or might have COVID-19.

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I cannot take pills by mouth due to a condition.

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My cancer has spread to my brain or its coverings.

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I have an autoimmune disease and have been treated for it in the last 2 years.

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I had a severe reaction to previous immune therapy that required stopping the treatment or long-term medication to manage.

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I still experience significant side effects from my previous cancer treatments.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 5 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 5 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 5 years for reporting.

Treatment Details

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

4Treatment groups

Experimental Treatment

Group I: Treatment Group C Dose Escalation and ExpansionExperimental Treatment3 Interventions

INCA00186 will be administered in combination with retifanlimab and INCB106385. INCA00186 will be administered every 2 to 4 weeks, retifanlimab every 4 weeks and INCB106385 once or twice daily.

Group II: Treatment Group B2 Dose Escalation and ExpansionExperimental Treatment2 Interventions

INCA00186 will be administered in combination with INCB106385. INCA00186 will be administered every 2 or 4 weeks and INCB106385 will be administered once or twice daily.

Group III: Treatment Group B1 Dose Escalation and ExpansionExperimental Treatment2 Interventions

INCA00186 will be administered in combination with retifanlimab. INCA00186 will be administered every 2 or 4 weeks and retifanlimab will be administered every 4 weeks.

Group IV: Treatment Group A Dose Escalation and ExpansionExperimental Treatment1 Intervention

INCA00186 will be administered as monotherapy every 2 or every 4 weeks.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Retifanlimab

2018

Completed Phase 2

~430

INCB106385

2021

Completed Phase 1

~60

0 / 23Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Common treatments for gastrointestinal cancers, particularly those involving immunotherapy, include immune checkpoint inhibitors and chimeric antigen receptor (CAR) T-cell therapies. Immune checkpoint inhibitors, such as anti-PD-1 and anti-CTLA-4 antibodies, work by blocking proteins that prevent T-cells from attacking cancer cells, thereby enhancing the immune response against tumors. CAR T-cell therapies involve modifying a patient's T-cells to express receptors that specifically target cancer cells. These treatments are significant for gastrointestinal cancer patients as they offer a targeted approach to boost the body's immune system to fight cancer, potentially leading to better outcomes and fewer side effects compared to traditional therapies.