INCA 0186 Combination Therapy for Cancer

No longer recruiting at 37 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: Immunosuppressants, Corticosteroids

Disqualifiers: Cardiac disease, CNS metastases, Autoimmune, others

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

Compensation: Varies

Number of Visits: 2

Duration: Dose escalation and expansion phase

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new cancer treatment to assess its safety and effectiveness against advanced solid tumors. It targets specific cancers, such as certain head and neck cancers and specific gastrointestinal cancers. The study tests a drug called INCA00186, both alone and in combination with other drugs, including Retifanlimab, an immunotherapy drug. The aim is to evaluate how well these combinations combat cancer. Individuals with CD8 T-cell-positive tumors, who have experienced disease progression after other treatments, might be suitable for this trial. As a Phase 1 trial, this research focuses on understanding 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 protocol does not specify if you must stop taking your current medications. However, you cannot participate if you are on certain treatments like strong CYP3A4 inhibitors or inducers, or if you've had recent chemotherapy, biological therapy, or targeted therapy within 28 days before the study starts.

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

Research shows that INCA00186 alone does not raise major safety concerns. It has been tested in patients with advanced solid tumors, and no significant safety issues emerged.

When combined with INCB106385, studies have assessed the safety and tolerability of this combination. The goal is to identify a dose that is safe and free from serious side effects. Additionally, combining INCA00186 with retifanlimab appears relatively safe. Retifanlimab, already approved by the FDA for certain cancers, has a well-understood safety profile.

The combination of all three drugs—INCA00186, INCB106385, and retifanlimab—aims to enhance the body's immune response against cancer. This combination remains in early testing, so a complete safety profile is not yet available. However, each drug has been studied separately and has shown manageable safety profiles.

Overall, these treatments are in the early stages of testing, and safety data collection is ongoing. Initial results are promising. It is important to consult a healthcare provider about potential risks and benefits before joining a trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination therapies involving INCA00186 because they offer potentially new ways to tackle cancer. Unlike standard therapies like chemotherapy and radiation, which often kill both healthy and cancerous cells, INCA00186 is used in combination with retifanlimab and INCB106385 to target cancer cells more precisely, potentially leading to fewer side effects. INCA00186, when combined with retifanlimab, a PD-1 inhibitor, and INCB106385, a novel oral immunomodulator, could enhance the immune system's ability to recognize and destroy cancer cells. This multi-pronged approach might improve response rates and lead to better outcomes for patients compared to single-agent therapies.

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

Research has shown that INCA00186 is a promising cancer treatment because it blocks a protein called CD73, which can aid tumor growth. Early studies suggest that INCA00186 can slow tumor growth, especially when combined with other drugs. In this trial, participants may receive INCA00186 alone or with other treatments. Retifanlimab, another drug in this trial, has already been shown to extend survival in people with certain cancers. Some participants will receive a combination of INCA00186 and Retifanlimab, while others will receive INCA00186 and INCB106385. When used together, INCA00186 and INCB106385 might enhance the immune system's ability to attack cancer cells. These combinations aim to increase treatment effectiveness by employing different methods to combat cancer. ^{3 6 7 8 9}

Who Is on the Research Team?

Ilona Rybicka, MD

Principal Investigator

Incyte Corporation

Are You a Good Fit for This Trial?

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.

Inclusion Criteria

Measurable disease according to RECIST v1.1.

Measurable disease according to RECIST v1.1

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

Exclusion Criteria

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

History or presence of an ECG abnormality that, in the investigator's opinion, is clinically meaningful

I haven't had radiation therapy in the last 28 days.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive INCA00186 as monotherapy or in combination with retifanlimab and/or INCB106385, with dosing every 2 to 4 weeks

Dose escalation and expansion phase

Visits every 2 to 4 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• INCA00186
• INCB106385
• Retifanlimab

Trial Overview 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.

How Is the Trial Designed?

Group I: Treatment Group C Dose Escalation and Expansion Experimental Treatment 3 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 Expansion Experimental Treatment 2 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 Expansion Experimental Treatment 2 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 Expansion Experimental Treatment 1 Intervention

INCA00186 will be administered as monotherapy every 2 or every 4 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

The combination of MEDI0680 and durvalumab was found to be safe and tolerable in patients with advanced clear-cell renal cell carcinoma, but it did not show improved efficacy compared to nivolumab alone, with objective response rates of 16.7% for the combination and 23.8% for nivolumab.

Both treatment groups had a median progression-free survival of 3.6 months, and a notable percentage of patients (23.8% in the combination group) discontinued treatment due to adverse events, highlighting the need for careful monitoring of side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Randomized Phase II Study of MEDI0680 in Combination with Durvalumab versus Nivolumab Monotherapy in Patients with Advanced or Metastatic Clear-cell Renal Cell Carcinoma. Voss, MH., Azad, AA., Hansen, AR., et al.[2023]

Retifanlimab is a programmed cell death 1 (PD-1) receptor-blocking antibody developed for treating solid tumors, showing promise both alone and in combination with other therapies.

It has received accelerated approval for adults with metastatic or recurrent locally advanced Merkel cell carcinoma, marking a significant milestone in its development.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Retifanlimab: First Approval. Kang, C.[2023]

The combination of ramucirumab and durvalumab was found to have manageable safety, with grade ≥3 treatment-related adverse events occurring in 32.1% of NSCLC, 37.9% of gastric/GEJ, and 42.9% of HCC patients, indicating that while there are risks, they are within acceptable limits for further study.

The treatment showed preliminary efficacy with an objective response rate of 11% for NSCLC and HCC, and 21% for gastric/GEJ, with better outcomes observed in patients with high PD-L1 expression, suggesting that this combination may be particularly beneficial for certain patient populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ramucirumab and durvalumab for previously treated, advanced non-small-cell lung cancer, gastric/gastro-oesophageal junction adenocarcinoma, or hepatocellular carcinoma: An open-label, phase Ia/b study (JVDJ). Bang, YJ., Golan, T., Dahan, L., et al.[2023]

Lenvatinib plus pembrolizumab had the highest rates of severe treatment-related adverse events (grade ≥3 TRAEs) and treatment discontinuation among the combination therapies for advanced renal cell carcinoma.

Nivolumab plus ipilimumab had the lowest rates of severe TRAEs but was linked to more endocrine-related adverse events, highlighting the need to balance efficacy with safety in treatment choices.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse events of systemic immune-based combination therapies in the first-line treatment of patients with metastatic renal cell carcinoma: systematic review and network meta-analysis. Quhal, F., Mori, K., Remzi, M., et al.[2023]

Musculoskeletal immune-related adverse events (Ir-AE) occur in about 6.13% of patients treated with immune checkpoint inhibitors (ICIs), with inflammatory arthritis being the most common manifestation, affecting 57.57% of those with Ir-AE.

Despite the occurrence of musculoskeletal Ir-AE, most patients (81%) can continue their ICI treatment, and those with these adverse events often show a favorable response to cancer treatment, indicating a potential link between these side effects and better tumor outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immune checkpoint inhibitor-induced musculoskeletal manifestations. Angelopoulou, F., Bogdanos, D., Dimitroulas, T., et al.[2021]

In a phase 1 trial involving 53 patients with advanced melanoma, the combination of nivolumab and ipilimumab resulted in a 40% objective response rate, with 65% of patients showing clinical activity, indicating significant effectiveness in tumor reduction.

The concurrent treatment had a manageable safety profile, with 53% of patients experiencing grade 3 or 4 adverse events, which were similar to those seen with monotherapy and generally reversible, suggesting that this combination therapy is a viable option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab plus ipilimumab in advanced melanoma. Wolchok, JD., Kluger, H., Callahan, MK., et al.[2022]

Immune checkpoint inhibitor combinations have significantly changed the treatment approach for metastatic clear-cell renal cell carcinoma, with four approved regimens for first-line therapy, including nivolumab plus ipilimumab for high-risk patients.

Choosing subsequent therapies after initial treatment is becoming complex, but there is potential for novel strategies targeting new pathways, such as hypoxia-inducible factor inhibitors, to improve patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapeutic sequencing in the era of first-line immune checkpoint inhibitor combinations, a novel challenge in patients with metastatic clear-cell renal cell carcinoma. Flippot, R., Gorgeu, V., Pujalte, M., et al.[2022]

The combination of vibostolimab and pembrolizumab is well tolerated by patients, indicating a favorable safety profile for this treatment regimen.

This combination therapy demonstrates antitumor activity, suggesting it may be an effective option for cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An Anti-TIGIT Antibody with a PD-1 Inhibitor Shows Promise in Solid Tumors. [2022]

The combination of sunitinib and tremelimumab in patients with metastatic renal cell carcinoma showed significant safety concerns, particularly with rapid-onset acute renal failure being the most common dose-limiting toxicity observed.

Despite the safety issues, the treatment demonstrated some efficacy, with 43% of evaluable patients achieving partial responses, indicating potential antitumor activity that warrants further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 1 dose-escalation trial of tremelimumab plus sunitinib in patients with metastatic renal cell carcinoma. Rini, BI., Stein, M., Shannon, P., et al.[2020]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04989387

Study of INCA 0186 in Subjects With Advanced Solid Tumors This is an open-label, nonrandomized, multicenter, dose escalation, and dose expansion first-in human (FIH) Phase 1 study to determine the safety, ...

2. onderzoekmetmensen.nl onderzoekmetmensen.nl/en/node/53794/pdf

A Phase 1, Open-Label, multicenter Study of INCA00186 ... The secondary objectives are: To evaluate the pharmacokinetics of INCA00186 as monotherapy or in combination with retifanlimab and/or.

3. clinicaltrial.be clinicaltrial.be/en/details/40979?per_page=100&only_recruiting=0&only_eligible=0&source=14

Study of INCA 0186 in Subjects With Advanced Solid ... A Phase 1, Open-Label, Multicenter Study of INCA00186 as Monotherapy or in Combination With Immunotherapy in Participants With Advanced Solid Tumors

4. researchgate.net researchgate.net/publication/352921208_Abstract_LB174_Discovery_and_preclinical_characterization_of_INCA00186_a_humanized_monoclonal_antibody_antagonist_of_CD73_as_a_cancer_immunotherapy

Discovery and preclinical characterization of INCA00186, a ... In summary, the data presented in this study demonstrates that INCA00186 is a potent CD73 antagonist and effectively attenuates adenosine induced ...

5. investor.incyte.com investor.incyte.com/static-files/41dd60b6-1668-4ebd-9b11-93c901aa8567

Data Highlights from Incyte's Adenosine Program from ... INCA00186 + INCB106385 significantly inhibits tumor growth in MDA ... immunotherapy for cancer patients. Page 18. PLANNED STUDIES FOR THE ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT04989387

Study of INCA 0186 in Subjects With Advanced Solid Tumors There were no safety concerns contributing to this decision. Study of INCA 0186 in Subjects With Advanced Solid Tumors. ClinicalTrials.gov ID NCT04989387.

7. withpower.com withpower.com/trial/phase-1-squamous-cell-carcinoma-of-head-and-neck-7-2021-2e583

INCA 0186 Combination Therapy for Cancer · Info for Participants The combination of ramucirumab and durvalumab was found to have manageable safety, with grade ≥3 treatment-related adverse events occurring in 32.1% of NSCLC, ...

8. aacrjournals.org aacrjournals.org/cancerres/article/81/13_Supplement/LB174/670119/Abstract-LB174-Discovery-and-preclinical

Discovery and preclinical characterization of INCA00186, a ... INCA00186 is a potent CD73 antagonist and effectively attenuates adenosine induced immunosuppression in the tumor microenvironment.

9. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2022-01925

Study of INCA 0186 in Subjects With Advanced Solid Tumors This is an open-label, nonrandomized, multicenter, dose escalation, and dose expansion first-in human (FIH) Phase 1 study to determine the safety, ...