A Phase 2 Study Evaluating INCB099280 in Participants With Advanced Cutaneous Squamous Cell Carcinoma

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

25 Oct 2023 → 25 Mar 2026

Decision date (initial)

2023-09-18

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

To determine the safety, tolerability, and preliminary efficacy of INCB099280 400 mg BID, 600 mg BID, and 800 mg BID in participants with advanced cSCC.

Secondary objectives 2

1. To determine the efficacy of INCB099280 400 mg BID, 600 mg BID, and 800 mg BID in participants with advanced cSCC.
2. To characterize the INCB099280 PK in plasma in participants with advanced cSCC.

Conditions and MedDRA coding

Treatment of immunotherapy-naive patients with previously untreated or recurrent locally advanced or metastatic cSCC not amenable to curative surgery and/or radiotherapy

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

1. Ability to comprehend and willingness to sign a written ICF for the study.
2. Age 18 years or older inclusive at the time of signing the ICF.
3. Histopathological diagnosis of cSCC. Note: Tumors arising on the cutaneous hair-bearing portion of the lip with extension to the dry red lip (vermilion) are eligible if the origin of the primary tumor is known and clearly documented as the cutaneous hair-bearing portion of the lip. Participants with mixed histology are eligible if the predominant histology is cSCC.
4. Previously untreated or recurrent locally advanced (without nodal metastases) or metastatic (distant or regional metastasis) cSCC not amenable to curative surgery and/or radiotherapy following consultation with a surgeon and/or radiation oncologist, respectively.
5. Measurable disease based on either radiographic imaging per RECIST 1.1 with at least 1 baseline lesion ≥ 10 mm in maximal diameter for metastatic disease or digital medical photography per WHO criteria with at least 1 baseline lesion in which both the longest diameter and the perpendicular diameter are ≥ 10 mm for externally visible disease.
6. ECOG performance status of 0 or 1 (see Section 8.3.4 of the protocol)
7. Baseline archival tumor specimen available or willingness to undergo a pretreatment tumor biopsy to obtain a specimen for retrospective biomarker analysis. Must be a tumor block or 15 unstained slides (6 slides minimum) from biopsy or resection of primary tumor or metastasis that are ≤ 1 year old (≤ 6 months for slides). It is preferred that the archival sample is from tissue obtained after completion of last treatment. Fine-needle aspirate and bone metastases samples are not acceptable
8. Life expectancy of > 3 months, in the opinion of the investigator.
9. Willingness to avoid pregnancy or fathering children based on the criteria below. a. Men must agree to take appropriate precautions to avoid fathering children (with at least 99% certainty) from screening through 100 days after the last dose of study drug (or longer as appropriate based on country-specific requirements) and must refrain from donating sperm during this period. Permitted methods that are at least 99% effective in preventing pregnancy (see Appendix A) should be communicated to the participants and their understanding confirmed. b. WOCBP must meet the following criteria: − Have a negative serum pregnancy test at screening and agree to take appropriate precautions to avoid pregnancy (with at least 99% certainty) from screening through 190 days after the last dose of study treatment. Permitted methods that are at least 99% effective in preventing pregnancy (see Appendix A) should be communicated to the participants and their understanding confirmed. − Refrain from donating oocytes from 30 days before the first dose of study drug until 90 days after the last dose.

Exclusion criteria 29

1. cSCC arising in the following locations: • Primary tumors of the vermilion only • Primary site of cancer on the penis, scrotum, and perianal region
2. 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.
3. CNS metastases requiring treatment and/or leptomeningeal disease. Note: Participants with untreated CNS metastases are excluded if any of the following apply: are symptomatic, require increasing steroids and/or a steroid dose of more than 1 mg of dexamethasone daily (or equivalent), or have lesions with significant edema. Note: Participants with treated CNS metastases are excluded if any of the following apply: CNS metastatic disease that is progressing, not clinically stable within 2 weeks of C1D1, or require increasing steroids and/or a steroid dose of more than 1 mg of dexamethasone daily (or equivalent).
4. 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).
5. Prior receipt of an anti–PD-1, anti–PD-L1, or anti–PD-L2 agent; treatment with an immune modulator (eg, CTLA-4, GITR, LAG3, TIM3, OX40, ICOS, IL-2, 4-1BB, CAR-T cell); or treatment with a BRAF inhibitor.
6. Received thoracic radiation of > 30 Gy within 6 months of the first dose of study treatment. Note: Participants must have recovered from all radiation-related toxicities to ≤ Grade 1 and not require corticosteroids.
7. Participation in another interventional clinical study while receiving INCB099280.
8. Treatment with anticancer medications or investigational drugs within the following intervals before the first administration of study drug: • At least 14 days for chemotherapy or targeted small-molecule therapy • At least 28 days for a prior monoclonal antibody used for anticancer therapy • At least 28 days or 5 half-lives (whichever is longer) before the first dose for all other investigational study drugs or devices Note: Participants receiving bisphosphonates and/or denosumab are eligible for enrollment.
9. 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)
10. History or evidence of interstitial lung disease, including noninfectious pneumonitis.
11. 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 gastric band
12. Any autoimmune disease requiring systemic treatment in the past 5 years, including corticosteroids of a daily dose exceeding 10 mg of prednisone or equivalent.
13. Diagnosis of primary immunodeficiency or receiving chronic systemic steroid therapy at a daily dose exceeding 10 mg of prednisone or equivalent.
14. HIV infection and any one or more of the following: CD4+ T-cell count < 200 cells/µL, detectable viral load, or antiretroviral therapy regimen containing moderate or potent CYP3A4/CYP3A5 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.
15. Active infection requiring systemic therapy, with the exception of HIV and hepatitis as noted.
16. History of organ transplantation, including allogeneic stem cell transplantation
17. Known hypersensitivity or severe reaction to any component of study drug or formulation components.
18. Postoperative complications preventing the participant from adhering to protocol assessments and procedures.
19. Receipt of systemic antibiotics within 28 days of first dose of study treatment.
20. Probiotic usage within 28 days of first dose of study treatment and while on study is prohibited.
21. Received a live vaccine within 28 days of the planned start of study drug.
22. Treatment with moderate and potent CYP3A4/CYP3A5 inhibitors or inducers (see Appendix E). Note: A washout period ≥ 10 days before the first dose of INCB099280 is required for prior treatment with CYP3A4/CYP3A5 inhibitors/inducers.
23. Unable to be weaned off of a prohibited medication as described in Section 6.6.3 before the initiation of study treatment
24. Laboratory values at screening as defined in Table 5.
25. Clinically significant ECG abnormality, including QTcF interval > 480 milliseconds. Note: If a single ECG tracing at screening is > 480 milliseconds, the average of a triplicate ECG may be used.
26. Active HBV or HCV infection defined as follows (testing must be performed to determine eligibility): a. Detectable HBV DNA and HBsAg positive. b. A positive HCV antibody and quantitative HCV RNA result greater than the lower limit of detection for the assay.
27. Pregnant, expecting to conceive, or breastfeeding starting with the screening visit through 190 days after the last dose of study treatment or expecting to father children starting with the screening visit through 100 days after the last dose of study treatment.
28. Any condition that would, in the investigator's judgment, interfere with full participation in the study, including administration of study drug and attending required study visits, pose a significant risk to the participant, or interfere with interpretation of study data
29. 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. Objective response, defined as having a best overall response of confirmed CR or PR by BICR per RECIST v1.1 or composite criteria for metastatic cSCC and per WHO criteria for locally advanced cSCC.
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 study drug discontinuation.

Secondary endpoints 6

1. Disease control, defined as having a best overall response of confirmed CR or PR, or SD, after a minimum of 15 weeks following the initiation of study treatment by BICR per RECIST v1.1 or composite criteria for metastatic cSCC and WHO criteria for locally advanced cSCC.
2. DOR, defined as the time from the earliest date of confirmed CR or PR to the earliest date of disease progression by BICR per RECIST v1.1 or composite criteria for metastatic cSCC and WHO criteria for locally advanced cSCC or death due to any cause if occurring sooner than progression.
3. TTR, defined as the time from the date of first dose to the earliest date of confirmed CR or PR by BICR per RECIST v1.1 or composite criteria for metastatic cSCC and WHO criteria for locally advanced cSCC.
4. PFS, defined as the time from the date of first dose to the earliest date of disease progression by BICR per RECIST v1.1 or composite criteria for metastatic cSCC and WHO criteria for locally advanced cSCC or death due to any cause if occurring sooner than progression.
5. OS, defined as the time from the date of first dose to death due to any cause.
6. INCB099280 concentration in plasma.

Investigational products

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

Test 1

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 6

Locations

7 EU/EEA countries · 45 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

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

Documents 81 files

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

Application history

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