INCA32459 for Advanced Cancer

No longer recruiting at 36 trial locations

Overseen By Incyte Corporation Call Center (US)

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Incyte Corporation

Must not be taking: Systemic steroids

Disqualifiers: Interstitial lung disease, Active autoimmune, 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 called INCA32459 for people with advanced cancers. The goal is to assess the treatment's safety and tolerability and to understand its effects on the body. The trial consists of two parts: the first part determines the optimal dose, while the second part focuses on individuals with specific cancers, such as melanoma and head and neck cancer. Suitable candidates have advanced cancer that has worsened after other treatments, including metastatic melanoma or PD-L1 positive head and neck cancer. As a Phase 1 trial, the research aims to understand how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot have had anticancer therapies or participated in another clinical study within 28 days before starting this trial. Chronic treatment with systemic steroids over 10 mg/day of prednisone or equivalent is also not allowed.

Is there any evidence suggesting that INCA32459 is likely to be safe for humans?

Research shows that INCA32459 is being tested for safety in people with advanced cancers. As a Phase 1 trial, this marks the first use of the treatment in humans. The goal is to determine the safest dosage.

While specific safety information is limited, early studies on similar treatments suggest that drugs targeting LAG-3 and PD-1, proteins that regulate the immune system, can be promising. These drugs have been used for other cancers and are generally well-tolerated. However, as a new treatment, INCA32459 may have unknown side effects.

This trial aims to identify potential issues and establish the optimal dose. Ensuring participant safety remains a top priority, and researchers will closely monitor for any side effects. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about INCA32459 because it could offer a new approach for treating advanced cancers like melanoma and squamous cell carcinoma of the head and neck (SCCHN). Unlike current treatments, such as checkpoint inhibitors or targeted therapies, INCA32459 might work by targeting a unique pathway or mechanism that's not yet addressed by existing drugs. This could potentially lead to improved outcomes for patients who don't respond well to the standard treatments. Additionally, the possibility of customizing dosage during the trial can help optimize the treatment's effectiveness and safety.

What evidence suggests that INCA32459 might be an effective treatment for advanced cancer?

Research has shown that INCA32459, a special type of antibody, may help treat certain advanced cancers. This antibody boosts the immune system's ability to fight tumors by blocking the pathways cancer cells use to hide from immune cells. Studies have found that targeting a protein called LAG-3 can improve the body's ability to fight cancer. When combined with blocking another protein, PD-1, the effect could be even stronger. This trial will test INCA32459 in different parts: Part 1 involves dose escalation to determine the optimal dose, while Part 2 includes dose expansion cohorts for specific cancers, such as unresectable or metastatic melanoma and recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN) that is PD-L1 positive. Early results suggest this treatment might be effective for these hard-to-treat cancers. Although this research is still in the early stages, the findings offer hope for patients with these conditions. ^{1 5 6 7 8}

Are You a Good Fit for This Trial?

This trial is for adults with certain advanced cancers who've had disease progression after standard treatments or can't tolerate them. It's open to those with specific types of melanoma and head/neck cancer, provided they haven't used LAG-3 therapy before and don’t have active brain metastases or autoimmune diseases requiring high-dose steroids.

Inclusion Criteria

My cancer is confirmed by lab tests and is advanced.

I am willing to have a new tumor biopsy.

Measurable disease according to RECIST v1.1

Exclusion Criteria

I do not have another cancer that is getting worse or needs treatment.

I still have side effects from previous treatments that are not mild.

I haven't had cancer treatment or been in a clinical study in the last 28 days.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Part 1 involves dose escalation to determine the recommended dose and maximum tolerated dose of INCA32459

Up to 12 months

Dose Expansion

Part 2 involves dose expansion to further evaluate safety, tolerability, and preliminary antitumor activity at the recommended dose(s)

Up to 12 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 12 months

What Are the Treatments Tested in This Trial?

Interventions

• INCA32459

Trial Overview The study tests INCA32459, a new bispecific antibody targeting LAG-3 and PD-1, in patients with select advanced malignancies. The first part determines the safest dose while the second part assesses its safety at that dose and how well it works against two specific types of tumors.

How Is the Trial Designed?

Group I: Part 2: Dose Expansion Cohort Disease Group 2 Experimental Treatment 1 Intervention

INCA32459 will be administered at the recommended dose or doses for expansion (RDE\[s\]) for recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN) that is PD-L1 positive.

Group II: Part 2: Dose Expansion Cohort Disease Group 1 Experimental Treatment 1 Intervention

INCA32459 will be administered at the recommended dose or doses for expansion (RDE\[s\]) for unresectable or metastatic melanoma.

Group III: Part 1: Dose Escalation Experimental Treatment 1 Intervention

INCA32459 will be administered at a protocol defined starting regimen intravenously. Subsequent dose regimens will be determined during study conduct.

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

In a study of 65 patients undergoing interventional oncology therapies combined with immune checkpoint inhibitors, only 10.8% experienced immune-related adverse events (irAEs), mostly mild and manageable, indicating a favorable safety profile for this combination treatment.

The study found no severe complications (grade 5) related to the procedures or irAEs within 90 days, suggesting that combining tumor-directed therapies with immune checkpoint inhibitors is safe and does not lead to unexpected toxicities.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Thermal Ablation, Embolization, and Selective Internal Radiation Therapy Combined with Checkpoint Inhibitor Cancer Immunotherapy: Safety Analysis. Leppelmann, KS., Mooradian, MJ., Ganguli, S., et al.[2021]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05577182

Study of INCA32459 a LAG-3 and PD-1 Bispecific Antibody ... This is a multicenter, open-label, single-arm study to investigate the safety, tolerability, PK, pharmacodynamics and preliminary activity of INCA32459 in ...

2. researchgate.net researchgate.net/publication/365213340_723_A_phase_1_first-in-human_open-label_multicenter_study_of_INCA32459_a_bispecific_anti-PD1_and_anti-LAG-3_antibody_in_patients_with_select_advanced_malignancies

723 A phase 1, first-in-human, open-label, multicenter study of ... Therefore, this study aims to assess the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary clinical efficacy of INCA32459, a bispecific ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12047404/

Advances in LAG3 cancer immunotherapeutics - PMC This review discusses the current understanding of LAG3 in regulating antitumor immunity and the ongoing clinical testing of LAG3 inhibition in cancer.

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12155519/

Emerging Immunotherapy Targets in Early Drug Development Immunotherapy has significantly changed the treatment paradigm for solid tumors, with immune checkpoint inhibitors now established in the management of many ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S1368837524004639

Immunotherapeutic strategies beyond the PD-1/PD-L1 ... This review offers a comprehensive overview of the existing immunotherapy strategies in HNSCC with a focus on TIM-3, TIGIT, LAG-3, and VISTA.

6. jitc.bmj.com jitc.bmj.com/content/jitc/10/Suppl_2/A756.full.pdf

723 A phase 1, first-in-human, open-label, multicenter ... Background Anti–programmed cell death (PD)-ligand (L)1 therapies have improved clinical outcomes in patients with various cancers.1.

7. investor.incyte.com investor.incyte.com/news-releases/news-release-details/data-incytes-oncology-portfolio-be-presented-society

Data From Incyte's Oncology Portfolio to Be Presented at ... Abstracts featuring data from its oncology portfolio will be presented at the upcoming Society for Immunotherapy of Cancer (SITC) 37th Annual Meeting.

8. synapse-patsnap-com.libproxy1.nus.edu.sg synapse-patsnap-com.libproxy1.nus.edu.sg/drug/cb6b3380c18f42799ac26dfa2ead4122

INCA32459 - Drug Targets, Indications, Patents - Synapse INCA32459: a LAG3 inhibitors, PD-1 inhibitors Drug, Initially developed by Incyte Corp., Now, its global highest R&D status is Phase 1, Mechanism: LAG3 ...