A Phase I Study of INCB099280 in Combination With Ipilimumab in Participants With Selected Solid Tumors

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Incyte Corp.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

completed 8 Nov 2024

Decision date (initial)

2024-02-20

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Incyte Corporation

External identifiers

EU CT number

2023-503243-34-00

ClinicalTrials.gov

NCT05909995

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

To determine the safety and tolerability and identify 1 or more RDEs of INCB099280 when administered in combination with ipilimumab in participants with advanced solid tumors.

Secondary objectives 2

1. To characterize the INCB099280 PK in plasma when administered in combination with ipilimumab in participants with advanced solid tumors.
2. To characterize the preliminary efficacy of INCB099280 in combination with ipilimumab in participants with advanced solid tumors.

Conditions and MedDRA coding

Solid tumor

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. Ability to comprehend and willingness to sign a written ICF for the study.
2. Aged 18 years or older at the time of signing the ICF.
3. Prior systemic therapy, diagnoses, and disease settings in the protocol
4. Must be willing and able to conform to and comply with all Protocol requirements, including all scheduled visits, Protocol procedures, and the ability to swallow oral medication.
5. An ECOG performance score of 0 or 1.
6. Life expectancy > 3 months, in the opinion of the investigator.
7. Histologically confirmed solid tumors with measurable disease per RECIST v1.1.
8. Willingness to avoid pregnancy or fathering children based on the criteria below. a. Male participants with reproductive potential must agree to take appropriate precautions to avoid fathering children from screening through 100 days after the last dose of study treatment (or longer as appropriate based on country-specific requirements) and must refrain from donating sperm during this period. Permitted methods in preventing pregnancy (see Appendix A) should be communicated to the participants and their understanding confirmed. b. Female participants who are WOCBP must have a negative serum pregnancy test at screening and a negative urine pregnancy test before the first dose on Day 1 and must agree to take appropriate precautions to avoid pregnancy from screening through 190 days after the last dose of study treatment and must refrain from donating oocytes during this period. Permitted methods in preventing pregnancy (see Appendix A) should be communicated to the participants and their understanding confirmed. c. Female participants not considered to be of childbearing potential as defined in Appendix A are eligible.

Exclusion criteria 28

1. Has a known history of an additional malignancy, except if the participant has undergone potentially curative therapy with no evidence of disease recurrence for 3 years since initiation of that therapy. Note: The time requirement for no evidence of disease for 3 years does not apply to participants who underwent successful definitive resection of basal cell carcinoma of the skin, superficial bladder cancer, squamous cell carcinoma of the skin, in situ cervical cancer, other noninvasive or indolent malignancies, or other in situ cancers.
2. Presence of gastrointestinal conditions that may affect drug absorption, as well as those that interfere with gastrointestinal transit, including gastric bypass surgery, gastric sleeve, or lap band.
3. Any autoimmune disease requiring systemic treatment in the past 5 years, including corticosteroids of a daily dose exceeding 10 mg of prednisone or equivalent.
4. Diagnosis of primary immunodeficiency or is receiving chronic systemic corticosteroid therapy of a daily dose exceeding 10 mg of prednisone or equivalent.
5. Known HIV infection with 1 or more of the following: CD4+ T-cell count < 200 cells/μL, detectable viral load per parameters of assay, or antiretroviral regimen containing potent and moderate CYP3A4/5 inhibitors or inducers. Note: Participants modifying their HIV regimen to include only drugs without CYP3A4/5 inhibitors or inducers must be on a stable regimen for > 28 days.
6. Has CNS metastases requiring treatment and/or leptomeningeal disease. Note: Participants with untreated CNS metastases are excluded if any of the followingapply: participants are symptomatic, metastases require increasing corticosteroids and/or a corticosteroid dose of more than 1 mg of dexamethasone daily (or equivalent), or participants have lesions with significant edema. Note: Participants with treated CNS metastases are excluded if any of the following apply: CNS metastatic disease is progressing, participants are not clinically stable within 2 weeks before Cycle 1 Day 1, or metastases require increasing corticosteroids and/or a corticosteroid dose of more than 1 mg of dexamethasone daily (or equivalent).
7. Toxicity from prior therapy that has not recovered to ≤ Grade 1 or baseline (with the exception of anemia not requiring transfusion support and any grade of alopecia).
8. For Part 1 (dose escalation): Prior receipt of an anti–CTLA-4 therapy. For Part 2 (dose expansion): Prior receipt of anti CTLA-4 therapy
9. Received thoracic radiation of > 30 Gy within 6 months before the first dose of study treatment. Note: Participants must have recovered from all radiationrelated toxicities to ≤ Grade 1 and not require corticosteroids.
10. Participation in another interventional clinical study while receiving INCB099280.
11. Treatment with anticancer medications or investigational drugs within the following intervals before the first administration of study treatment: a. At least 14 days for chemotherapy or targeted smallmolecule therapy. b. At least 28 days for a prior monoclonal antibody used for anticancer therapy. c. At least 28 days or 5 half-lives (whichever is longer) for all other investigational study drugs or devices. Note: Participants receiving bisphosphonates and/or denosumab are eligible for enrollment.
12. Participants with impaired cardiac function or clinically significant cardiac disease: • New York Heart Association Class III or IV cardiac disease, including preexisting clinically significant ventricular arrhythmia, congestive heart failure, or cardiomyopathy • Unstable angina pectoris • Acute myocardial infarction ≤ 6 months before study participation • Other clinically significant heart disease (ie, uncontrolled ≥ Grade 3 hypertension)
13. History or evidence of interstitial lung disease including noninfectious pneumonitis.
14. Active infection requiring systemic therapy, with the exception of HIV and hepatitis as noted.
15. History of organ transplantation, including allogeneic stem cell transplantation.
16. 15. Anamnéza transplantácie orgánov vrátane alogénnej transplantácie kmeňových buniek
17. Postoperative complications preventing the participant from adhering to Protocol assessments and procedures.
18. Use of systemic antibiotics within 28 days before the first dose of study treatment.
19. Use of probiotic supplements within 28 days before the first dose of study treatment.
20. Received a live vaccine within 28 days before the planned start of study treatment. Note: Examples of live vaccines include but are not limited to the following: measles, mumps, rubella, chickenpox/zoster, yellow fever, rabies, BCG, and typhoid. Seasonal influenza vaccines for injection are generally killed-virus vaccines and are allowed; however, intranasal influenza vaccines are live, attenuated vaccines and are not allowed.
21. Treatment with potent and moderate CYP3A4/5 inhibitors or inducers (see Appendix D). Note: A washout period ≥ 10 days before the first dose of study treatment is required for prior treatment with potent and moderate CYP3A4/5 inhibitors/inducers.
22. Unable to be weaned off of a prohibited medication as described in Section 6.7.3 before the initiation of study treatment.
23. Participants with laboratory values at screening defined in Table 7.
24. Clinically significant ECG abnormality, including average QTcF interval > 480 milliseconds of triplicate ECGs.
25. Active HBV or HCV defined as follows (testing must be performed to determine eligibility): a. Detectable HBV DNA (viral load) and HBsAg positive. b. Participants with chronic HBV infection with active disease who meet the criteria for anti-HBV therapy are required to be on a suppressive antiviral therapy prior to initiation of study treatment. c. Positive anti-HCV result and quantitative HCV RNA (viral load) result greater than the lower limit of detection for the assay. Note: Participants previously treated for HCV with clearance are specifically allowed in the study.
26. Female participants who are breastfeeding from the screening visit through 190 days after the last dose of study treatment.
27. Any condition that would, in the investigator's judgment, interfere with full participation in the study, including administration of study treatment and attending required study visits; pose a significant risk to the participant; or interfere with interpretation of study data.
28. The following participants are excluded in France: vulnerable populations according to article L.1121-6 of the French Public Health Code and adults under legal protection, or who are unable to express their consent per article L.1121-8 of the French Public Health Code, not affiliated to a social security per article L.1121-8-1 of the French Public Health Code.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 3

1. Occurrence of DLTs
2. Incidence of TEAEs, assessed by physical examinations, changes in vital signs and ECGs, and analysis of clinical laboratory samples
3. Incidence of TEAEs leading to dose interruption, dose reduction, or discontinuation of either of the study drugs

Secondary endpoints 4

1. Concentration of INCB099280 in plasma
2. Objective response, defined as having a best overall response of CR or PR by investigator assessment per RECIST v1.1.
3. Disease control, defined as having a best overall response of CR or PR, or SD of ≥ 15 weeks after initiation of study treatment, by investigator assessment per RECIST v1.1.
4. DOR, defined as the time from the earliest date of CR or PR until the earliest date of disease progression (by investigator assessment per RECIST v1.1) or death due to any cause if occurring sooner than progression.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Incyte Corp.

Sponsor organisation

Incyte Corp.

Address

1801 Augustine Cut Off

City

Wilmington

Postcode

19803-4404

Country

United States

Scientific contact point

Organisation

Incyte Corp.

Contact name

Clinical Trial Information

Public contact point

Organisation

Incyte Corp.

Contact name

Clinical Trial Information

Third parties 3

Sponsor responsibilities

Article 77 compliance

Incyte Corp.

Contact point sponsor

Incyte Corp.

Article 77 implementation

Incyte Corp.

Locations

3 EU/EEA countries · 5 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 2 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

3 submissions — initial application plus substantial / non-substantial modifications