INCA 0186 Combination Therapy for Cancer

Recruiting at 34 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

57 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

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.

What evidence supports the effectiveness of the drug INCA 0186 Combination Therapy for Cancer?

Research shows that combining immune checkpoint inhibitors, like those in INCA 0186, with other treatments can enhance their ability to fight tumors and help more patients respond to treatment. Similar combinations have shown promise in treating various cancers, suggesting potential effectiveness for INCA 0186. ^{1 2 3 4 5}

What safety data exists for INCA 0186 Combination Therapy for Cancer?

Immune checkpoint inhibitors, like those in INCA 0186, can cause immune-related side effects, including joint pain, muscle inflammation, and heart issues. These side effects are often mild to moderate, and treatment can usually continue. However, some patients may need additional medications to manage these effects. ^{6 7 8 9 10}

What makes the INCA 0186 drug combination unique for cancer treatment?

The INCA 0186 combination therapy is unique because it includes Retifanlimab, a programmed cell death 1 receptor-blocking antibody, which has shown promise in treating solid tumors and has received accelerated approval for Merkel cell carcinoma. This combination approach aims to enhance the effectiveness of immune checkpoint inhibitors by using them together with other agents, potentially broadening the range of patients who can benefit from such treatments. ^{3 11 12 13 14}

Research Team

Ilona Rybicka, MD

Principal Investigator

Incyte Corporation

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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 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]

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]

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]

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]

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 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]

References

1. France 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. [2022]

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

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

3. England 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). [2023]

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

Nivolumab plus ipilimumab in advanced melanoma. [2022]

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

Phase 1 dose-escalation trial of tremelimumab plus sunitinib in patients with metastatic renal cell carcinoma. [2020]

6. United States 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. [2023]

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

Rheumatic immune-related adverse events associated with immune checkpoint inhibitors compared with placebo in oncologic patients: a systemic review and meta-analysis. [2022]

8. Germany pubmed.ncbi.nlm.nih.gov

Immune checkpoint inhibitor-induced musculoskeletal manifestations. [2021]

9. England pubmed.ncbi.nlm.nih.gov

How can we manage the cardiac toxicity of immune checkpoint inhibitors? [2021]

10. England pubmed.ncbi.nlm.nih.gov

Histological diagnosis of immune checkpoint inhibitor induced acute renal injury in patients with metastatic melanoma: a retrospective case series report. [2021]

11. New Zealand pubmed.ncbi.nlm.nih.gov

Retifanlimab: First Approval. [2023]

12. United States 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. [2023]

13. England pubmed.ncbi.nlm.nih.gov

Tyrosine kinase inhibitors and immunotherapy combinations in renal cell carcinoma. [2023]

14. England pubmed.ncbi.nlm.nih.gov

An update on safety evaluation of immune-based combinations in patients with advanced renal cell carcinoma. [2023]