What side effects are associated with this type of intervention?

Common treatments for colorectal cancer involving immune checkpoint inhibitors like ipilimumab, which blocks CTLA-4, often lead to immune-related adverse events (irAEs). These include colitis, dermatitis, hepatitis, endocrinopathies, and pneumonitis. These side effects arise because the immune system, while targeting cancer cells, can also attack normal tissues. Combination therapies with other immune checkpoint inhibitors or targeted therapies can exacerbate the incidence and severity of these side effects.

What prior FDA approvals exist?

The FDA has approved several immune checkpoint inhibitors for the treatment of colorectal cancer, particularly for tumors with deficient DNA mismatch repair (dMMR) or high microsatellite instability (MSI-H). Pembrolizumab (Keytruda), a PD-1 inhibitor, and nivolumab (Opdivo), another PD-1 inhibitor, have received approval for these specific types of colorectal cancer. Additionally, the combination of nivolumab and ipilimumab (Yervoy), a CTLA-4 inhibitor, has been approved for dMMR/MSI-H colorectal cancer. These treatments enhance the immune system's ability to target and destroy cancer cells by blocking inhibitory pathways that prevent immune activation.

What other types of research exist?

Promising novel alternatives for colorectal cancer patients considering treatment in 2024 include: 1) Pembrolizumab, an anti-PD-1 antibody, especially for patients with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR). 2) Dostarlimab, another anti-PD-1 antibody, for patients with dMMR tumors. 3) Combination therapies involving nivolumab (anti-PD-1) and ipilimumab (anti-CTLA-4) for enhanced immune response. These alternatives have shown efficacy in specific biomarker-defined subsets of colorectal cancer patients.

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INCB 99280 + Ipilimumab for Solid Cancers

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

Must have histologically confirmed solid tumors with measurable disease per RECIST v1.1

ECOG performance score of 0 or 1

Must not have

Diagnosis of immunodeficiency or receiving chronic systemic steroid therapy at a daily dose exceeding 10 mg of prednisone or equivalent

Received thoracic radiation within 6 months of the first dose of study treatment

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 2 years

Awards & highlights

No Placebo-Only Group

Summary

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.

Who is the study for?

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.

What is being tested?

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.

What are the potential side effects?

Potential side effects may include immune-related reactions due to Ipilimumab such as inflammation in organs, skin rash, digestive issues; fatigue; changes in liver function; hormonal gland problems; and increased risk of infection.

Eligibility Criteria

Inclusion Criteria

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

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

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I am fully active or can carry out light work.

Exclusion Criteria

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

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

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I had chest radiation therapy within the last 6 months.

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I have a history of lung conditions not caused by infections.

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I am not in another clinical trial while taking INCB099280.

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I am not taking probiotics and will not during the study.

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I have brain metastases or leptomeningeal disease needing treatment.

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I have had an organ or stem cell transplant.

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I have heart problems that affect my daily life.

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I have had another type of cancer in the past.

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I am currently being treated for an infection.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 2 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~2 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and 2 years for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Incidence of TEAEs

Secondary study objectives

Disease control

Duration of Response

Objective response

Side effects data

From 2024 Phase 3 trial • 529 Patients • NCT02017717

80%

Fatigue

70%

Diarrhoea

70%

Headache

40%

Vomiting

40%

Aspartate aminotransferase increased

40%

Rash maculo-papular

40%

Alanine aminotransferase increased

40%

Lipase increased

30%

Partial seizures

30%

Hemiparesis

30%

Gait disturbance

30%

Fall

30%

Cough

30%

Dry skin

30%

Amylase increased

30%

Nausea

30%

Confusional state

20%

Malignant neoplasm progression

20%

Pyrexia

20%

Candida infection

20%

Mucosal infection

20%

Decreased appetite

20%

Back pain

20%

Dysphonia

20%

Hypotension

20%

Colitis

20%

Hyperthyroidism

20%

Oedema peripheral

20%

Muscular weakness

20%

Hypothyroidism

10%

Tinnitus

10%

Cushingoid

10%

Diabetic ketoacidosis

10%

Procedural haemorrhage

10%

Blood bilirubin increased

10%

Bradycardia

10%

Sinus tachycardia

10%

Hyperglycaemia

10%

Hypocalcaemia

10%

Neck pain

10%

Brain oedema

10%

Hydrocephalus

10%

Lethargy

10%

Seizure

10%

Hypertension

10%

Palpitations

10%

Cheilitis

10%

Presyncope

10%

Face oedema

10%

Oedema

10%

Conjunctivitis

10%

Enterocolitis infectious

10%

Oral candidiasis

10%

Pneumonia

10%

Sinusitis

10%

Staphylococcal infection

10%

Blood alkaline phosphatase increased

10%

Spinal pain

10%

Tremor

10%

Dizziness

10%

Dysarthria

10%

Urinary retention

10%

Dyspnoea exertional

10%

Nasal congestion

10%

Pneumonitis

10%

Dermatitis

10%

Erythema

10%

Rash

10%

Klebsiella infection

10%

Hypomagnesaemia

10%

Syncope

10%

Haemorrhage intracranial

10%

Pancreatitis

10%

Cholecystitis

10%

Upper respiratory tract infection

10%

Acute kidney injury

10%

Dermatitis bullous

10%

Lymphopenia

10%

Optic nerve disorder

10%

Visual impairment

10%

Dehydration

10%

Hypokalaemia

10%

Scoliosis

10%

Cognitive disorder

10%

Memory impairment

10%

Hallucination

10%

Insomnia

10%

Irritability

10%

Urinary incontinence

10%

Dyspnoea

10%

Dermatitis acneiform

10%

Pelvic venous thrombosis

10%

Sepsis

100%

80%

60%

40%

20%

Study treatment Arm

Cohort 1: Arm N1+I3

Cohort 2: Arm B

Part A Cohort 1c: Arm N3+RT+TMZ

Part A Cohort 1d: Arm N3+RT

Part B Cohort 1c: Arm N3+RT+TMZ

Part B Cohort 1d: Arm N3+RT

Cohort 1: Arm N3

Cohort 1b: Arm N3+I1

Cohort 2: Arm N3

Awards & Highlights

No Placebo-Only Group

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

Trial Design

2Treatment groups

Experimental Treatment

Group I: Dose ExpansionExperimental Treatment1 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 EscalationExperimental Treatment1 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

0 / 12Eligibility 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 colorectal cancer include chemotherapy, targeted therapies, and immune checkpoint inhibitors. Chemotherapy, such as fluoropyrimidines, works by interfering with DNA synthesis, thereby inhibiting cancer cell growth. Targeted therapies, like anti-EGFR and anti-VEGF agents, block specific molecules involved in tumor growth and angiogenesis. Immune checkpoint inhibitors, such as ipilimumab (which blocks CTLA-4) and pembrolizumab (which targets PD-1), enhance the immune system's ability to recognize and destroy cancer cells. These treatments are crucial for colorectal cancer patients as they offer multiple avenues to combat the disease, potentially improving survival rates and quality of life.

Standard therapies: solutions for improving therapeutic effects of immune checkpoint inhibitors on colorectal cancer.