INCB186748 for Solid Tumors

Recruiting at 8 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: KRAS inhibitors

Disqualifiers: Invasive malignancy, Organ transplant, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: Up to approximately 12 months

308 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to evaluate INCB186748 in Participants With Advanced or Metastatic Solid Tumors With KRAS G12D Mutation.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the drug INCB186748 for solid tumors?

The research highlights that immune checkpoint inhibitors (ICIs), which are similar to INCB186748, have shown effectiveness in treating various solid tumors by improving survival rates and disease control, even in patients with poor health status. Additionally, combining ICIs with other targeted therapies has enhanced antitumor activity in several solid tumor types. ^{1 2 3 4 5}

What makes the drug INCB186748 unique for treating solid tumors?

The drug INCB186748 is unique because it is part of a new wave of targeted therapies that directly affect the genetic or immunological changes in tumors, potentially offering more personalized and effective treatment options compared to traditional chemotherapy. ^{3 6 7 8 9}

Research Team

Incyte Medical Monitor

Principal Investigator

Incyte Corporation

Eligibility Criteria

This trial is for adults with advanced or metastatic solid tumors that have a specific genetic change called KRAS G12D mutation. Participants can join if they've had limited prior treatments, depending on the study part they qualify for. They must have tried standard treatments without success, be intolerant to them, or have no other treatment options.

Inclusion Criteria

Cohort-specific requirements as follows:

Parts 2a and 2b: Combination Group 1 (INCB186748 in combination with cetuximab): Diagnosis of PDAC or Diagnosis of CRC and Prior treatment in the advanced setting with a fluoropyrimidine-based chemotherapy regimen containing either oxaliplatin or irinotecan and In Part 2a: ≤ 3 prior standard regimens; In Part 2b: ≤ 2 prior standard regimens; Combination Group 2 (INCB186748 in combination with GEMNabP) and Combination Group 3 (INCB186748 in combination with mFOLFIRINOX): Diagnosis of PDAC; ≤ 1 prior standard systemic regimen for pancreatic cancer; Measurable disease according to RECIST v1.1; ECOG performance status score of 0 or 1

I am 18 years old or older.

Exclusion Criteria

Significant, uncontrolled medical condition

History or presence of an ECG abnormality

I have been treated with a KRAS inhibitor before.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive INCB186748 in various experimental arms including dose escalation and expansion, both as monotherapy and in combination with other treatments

Up to approximately 12 months

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessment of treatment-emergent adverse events and duration of response

Up to approximately 12 months and 60 days

Treatment Details

Interventions

• INCB186748

Trial Overview The trial is testing INCB186748 alone and in combination with other cancer drugs like Cetuximab, GEMNabP, and mFOLFIRINOX. It aims to see how well these treatments work in patients whose tumors carry the KRAS G12D mutation.

Participant Groups

Group I: Part 2b: Dose Expansion combination Experimental Treatment 4 Interventions

INCB186748 in combination at the protocol-defined dose strength based on cohort assignment.

Group II: Part 2a: Dose Escalation combination Experimental Treatment 4 Interventions

INCB186748 in combination at the protocol-defined dose strength based on cohort assignment.

Group III: Part 1d: Food-Effect Experimental Treatment 1 Intervention

Evaluate food effect on drug exposure as defined in the protocol.

Group IV: Part 1c: Pharmacodynamic cohort Experimental Treatment 1 Intervention

INCB186748 at the protocol-defined dose strength based on cohort assignment.

Group V: Part 1b: Dose Expansion monotherapy Experimental Treatment 1 Intervention

INCB186748 at the protocol-defined dose strength based on cohort assignment.

Group VI: Part 1a: Dose Escalation monotherapy Experimental Treatment 1 Intervention

INCB186748 at the protocol-defined dose strength based on cohort assignment.

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

Combining immune checkpoint inhibitors (ICIs) with signal transduction inhibitors, like antiangiogenic therapies, has shown enhanced antitumor activity in various solid tumors, leading to regulatory approvals for treatments in cancers such as endometrial and kidney cancer.

Despite these advancements, many patients still experience disease progression after combination treatments, highlighting the need for new strategies to overcome resistance to immunotherapy, which has prompted the development of consensus definitions for resistance to multiagent ICI combinations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Society for Immunotherapy of Cancer (SITC) consensus definitions for resistance to combinations of immune checkpoint inhibitors with targeted therapies. Atkins, MB., Ascierto, PA., Feltquate, D., et al.[2023]

In a study of 578 patients with various solid tumors treated with immune checkpoint inhibitors, the Lung Immune Prognostic Index (LIPI) was found to be a strong predictor of overall survival (OS) and progression-free survival (PFS), with median OS of 22.8 months for good LIPI compared to only 2.5 months for poor LIPI.

The findings suggest that LIPI may be applicable beyond non-small cell lung cancer, indicating its potential as a universal prognostic tool for patients receiving immune checkpoint inhibitors, regardless of tumor type.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Lung Immune Prognostic Index Discriminates Survival Outcomes in Patients with Solid Tumors Treated with Immune Checkpoint Inhibitors. Meyers, DE., Stukalin, I., Vallerand, IA., et al.[2020]

Targeted and immunological therapies have significantly improved survival rates in patients with solid tumors, demonstrating the effectiveness of treatments that focus on specific genetic and immunological changes in tumors.

Current clinical trials are exploring the optimal timing and sequencing of these therapies, which include various approved agents for cancers like prostate, breast, lung, and melanoma, indicating a shift towards more personalized cancer treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Pharmacotherapy of solid tumors. New hopes and frustrations]. Grünwald, V., Rickmann, M.[2021]

In a study of 155 patients with advanced solid tumors, those with a better performance status (ECOG PS 0-1) had a median overall survival (OS) of 9.1 months, compared to only 2.9 months for those with poorer performance status (ECOG PS 2-4), indicating that performance status significantly impacts treatment outcomes with immune checkpoint inhibitors (ICIs).

Despite having a poor performance status, 27.3% of patients in the study were still alive after one year, and the treatment was generally well-tolerated, with 84.6% of patients experiencing no severe toxicities, suggesting that ICIs can be a safe and effective option for this patient group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immune checkpoint inhibitors in patients with solid tumors and poor performance status: A prospective data from the real-world settings. Kapoor, A., Noronha, V., Patil, VM., et al.[2023]

A meta-analysis of 60 studies involving 35,020 patients found that immunotherapy significantly improves overall survival and progression-free survival in patients with ECOG performance status 0 or 1, indicating its effectiveness across these groups.

The benefits of immunotherapy were consistent across various treatment settings and types, suggesting that immune checkpoint inhibitors and combinations are effective regardless of the patient's initial performance status.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The impact of ECOG performance status on efficacy of immunotherapy and immune-based combinations in cancer patients: the MOUSEION-06 study. Mollica, V., Rizzo, A., Marchetti, A., et al.[2023]

Immunotherapy, particularly immune checkpoint inhibitors, has significantly improved treatment outcomes for high-risk resectable and metastatic melanoma, showcasing its effectiveness across various cancer types.

The success of immunotherapy in melanoma has led to its approval and evaluation in other solid tumors, indicating a broader application of these therapies in both early and advanced stages of cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Current Landscape of Immune Checkpoint Inhibition for Solid Malignancies. Keung, EZ., Wargo, JA.[2020]

Cadonilimab, a bispecific PD-1/CTLA-4 antibody, demonstrated a manageable safety profile with 28% of patients experiencing grade 3-4 treatment-related adverse events, indicating it can be safely administered to patients with advanced solid tumors.

In a phase 2 trial, cadonilimab showed promising antitumor activity, with an objective response rate of 32.3% in cervical cancer patients, suggesting its potential effectiveness in treating advanced solid tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and antitumour activity of cadonilimab, an anti-PD-1/CTLA-4 bispecific antibody, for patients with advanced solid tumours (COMPASSION-03): a multicentre, open-label, phase 1b/2 trial. Gao, X., Xu, N., Li, Z., et al.[2023]

Pembrolizumab, a PD-1 inhibitor, has received accelerated FDA approval for treating both adult and pediatric patients with solid tumors that are mismatch repair-deficient or microsatellite instability-high.

This approval marks a significant milestone as it is the first instance where the FDA has approved a cancer treatment based on a common biomarker rather than the specific type of tumor.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First Tissue-Agnostic Drug Approval Issued. [2021]

References

1. England pubmed.ncbi.nlm.nih.gov

Society for Immunotherapy of Cancer (SITC) consensus definitions for resistance to combinations of immune checkpoint inhibitors with targeted therapies. [2023]

2. Switzerland pubmed.ncbi.nlm.nih.gov

The Lung Immune Prognostic Index Discriminates Survival Outcomes in Patients with Solid Tumors Treated with Immune Checkpoint Inhibitors. [2020]

3. Germany pubmed.ncbi.nlm.nih.gov

[Pharmacotherapy of solid tumors. New hopes and frustrations]. [2021]

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

Immune checkpoint inhibitors in patients with solid tumors and poor performance status: A prospective data from the real-world settings. [2023]

5. Italy pubmed.ncbi.nlm.nih.gov

The impact of ECOG performance status on efficacy of immunotherapy and immune-based combinations in cancer patients: the MOUSEION-06 study. [2023]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Immune Checkpoint Inhibitors Combined with Targeted Therapy: The Recent Advances and Future Potentials. [2023]

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

The Current Landscape of Immune Checkpoint Inhibition for Solid Malignancies. [2020]

8. England pubmed.ncbi.nlm.nih.gov

Safety and antitumour activity of cadonilimab, an anti-PD-1/CTLA-4 bispecific antibody, for patients with advanced solid tumours (COMPASSION-03): a multicentre, open-label, phase 1b/2 trial. [2023]

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

First Tissue-Agnostic Drug Approval Issued. [2021]