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A Phase 1 Study Exploring the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of INCB099280 in Participants With Select Advanced Solid Tumors
(Protocol No. : INCB 99280-112)

A Phase 1 Study Exploring the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of INCB099280 in Participants With Select Advanced Solid Tumors

182

Median age: 63.0 years (range: 21.0 to 86.0 years). Sex: Female54.4%, Male 45.6%

Started: 182 participants Completed: 7 participants Not completed: 175 participants

[Number of deaths (all causes)] Part 1 - 100 mg once daily (QD): 1/3 participants Part 1 - 200 mg QD: 2/3 participants Part 1 - 200 mg twice daily (BID): 0/3 participants Parts 1 and 2 - 300 mg BID: 11/37 participants Parts 1 and 2 - 400 mg BID: 10/50 participants Part 1 - 600 mg QD: 2/9 participants Part 2 - 600 mg BID: 6/23 participants Parts 1 and 2 - 800 mg QD: 6/24 participants Parts 1 and 2 - 800 mg BID: 6/30 participants [Number of participants with any serious adverse events (%)] Part 1 - 100 mg QD: 0/3 participants (0.00) Part 1 - 200 mg QD: 1/3 participants (33.33) Part 1 - 200 mg BID: 0/3 participants (0.00) Parts 1 and 2 - 300 mg BID: 16/37 participants (43.24) Parts 1 and 2 - 400 mg BID: 11/50 participants (22.00) Part 1 - 600 mg QD: 3/9 participants (33.33) Part 2 - 600 mg BID: 7/23 participants (30.43) Parts 1 and 2 - 800 mg QD: 4/24 participants (16.67) Parts 1 and 2 - 800 mg BID: 10/30 participants (33.33) [Number of participants with any non-serious adverse events (%)] Part 1 - 100 mg QD: 2/3 participants (66.67) Part 1 - 200 mg QD: 3/3 participants (100.00) Part 1 - 200 mg BID: 3/3 participants (100.00) Parts 1 and 2 - 300 mg BID: 37/37 participants (100.00) Parts 1 and 2 - 400 mg BID: 43/50 participants (86.00) Part 1 - 600 mg QD: 9/9 participants (100.00) Part 2 - 600 mg BID: 22/23 participants (95.65) Parts 1 and 2 - 800 mg QD: 23/24 participants (95.83) Parts 1 and 2 - 800 mg BID: 30/30 participants (100.00)

Primary Outcome Measures [Number of participants with any treatment-emergent adverse event (TEAE) ] Part 1 - 100 mg QD: 3/3 participants Part 1 - 200 mg QD: 3/3 participants Part 1 - 200 mg BID: 3/3 participants Part 1 - 600 mg QD: 9/9 participants Parts 1 and 2 - 300 mg BID: 37/37 participants Parts 1 and 2 - 400 mg BID: 46/50 participants Part 2 - 600 mg BID: 23/23 participants Parts 1 and 2 - 800 mg QD: 23/24 participants Parts 1 and 2 - 800 mg BID: 30/30 participants [Number of participants with any >=Grade 3 TEAE] Part 1 - 100 mg QD: 1/3 participants Part 1 - 200 mg QD: 2/3 participants Part 1 - 200 mg BID: 0/3 participants Part 1 - 600 mg QD: 4/9 participants Parts 1 and 2 - 300 mg BID: 16/37 participants Parts 1 and 2 - 400 mg BID: 13/50 participants Part 2 - 600 mg BID: 11/23 participants Parts 1 and 2 - 800 mg QD: 10/24 participants Parts 1 and 2 - 800 mg BID: 12/30 participants [Number of participants with any dose-limiting toxicity] Part 1 - 100 mg QD: 0/3 participants Part 1 - 200 mg QD: 0/3 participants Part 1 - 200 mg BID: 0/3 participants Part 1 - 300 mg BID: 0/10 participants Part 1 - 400 mg BID: 0/12 participants Part 1 - 600 mg QD: 1/9 participants Part 1 - 800 mg QD: 0/10 participants Part 1 - 800 mg BID: 1/12 participants Secondary Outcome Measures INCB099280 was absorbed following oral dose administration with median plasma tmax values achieved approximately 2 hours postdose. Plasma exposure to INCB099280 increased approximately in proportion to the dose administration within the range of 100 to 800 mg QD or 200 to 800 mg BID. Steady state was achieved by Day 8 of the first treatment cycle.

In general, INCB099280 was well tolerated in participants with advanced or metastatic select solid tumor types. There were no safety concerns related to INCB099280 .

No

https://jrct.mhlw.go.jp/latest-detail/jRCT2031220663

Ono Shintaro

Incyte Biosciences Japan G.K.

Tokyo Midtown Hibiya, 1-1-2 Yurakucho, Chiyoda-ku, Tokyo, Japan

jpmedinfo@incyte.com

Medical Information Center

Incyte Biosciences Japan G.K.

Tokyo Midtown Hibiya, 1-1-2 Yurakucho, Chiyoda-ku, Tokyo, Japan

+81-120-094-139

jpmedinfo@incyte.com

Complete

Mar. 15, 2023

Interventional

non-randomized controlled trial

open(masking not used)

uncontrolled control

single assignment

treatment purpose

1. Must have disease progression after treatment with available therapies that are known to confer clinical benefit or must be intolerant to or ineligible for standard treatment.
2. Histologically confirmed advanced solid tumors (protocol-defined select solid tumors) with measurable lesions per Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST v1.1) that are considered nonamenable to surgery or other curative treatments or procedures.
3. Eastern Cooperative Oncology Group performance status score of 0 or 1.
4. Life expectancy > 12 weeks.
5. Willingness to avoid pregnancy or fathering children.

1. Laboratory values outside the Protocol-defined ranges.
2. Clinically significant cardiac disease.
3. History or presence of an electrocardiogram that, in the investigator's opinion, is clinically meaningful.
4. Untreated brain or central nervous system (CNS) metastases or brain or CNS metastases that have progressed (eg, evidence of new or enlarging brain metastasis or new neurological symptoms attributable to brain or CNS metastases).
5. Known additional malignancy that is progressing or requires active treatment.
6. Has not recovered to <= Grade 1 or baseline from toxic effects of prior therapy (including prior IO) and/or complications from prior surgical intervention before starting study treatment.
7. Prior receipt of an anti-PD-L1 therapy.
8. Treatment with anticancer medications or investigational drugs within protocol-defined intervals before the first administration of study drug.
9. A 28-day washout for systemic antibiotics is required.
10. Probiotic usage while on study and during screening is prohibited.
11. Active infection requiring systemic therapy.
12. Known history of Human Immunodeficiency Virus (HIV)
13. Evidence of hepatitis B virus or hepatitis C virus infection or risk of reactivation.

Both

Advanced Solid Tumor

Cohort 1:
Participants with select solid tumors who are immunotherapy treatment-naive.
INCB099280 administered orally in 25 mg or 100 mg tablets once daily or twice daily on each day of each 28-day cycle.
Cohort 2:
Participants with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR) tumors who are immunotherapy treatment-naive.
INCB099280 administered orally in 25 mg or 100 mg tablets once daily or twice daily on each day of each 28-day cycle.
Cohort 3:
Participants with progression of any solid tumor treated with an approved anti-PD-1 monoclonal antibody therapy.
INCB099280 administered orally in 25 mg or 100 mg tablets once daily or twice daily on each day of each 28-day cycle.

Number of treatment-emergent adverse events

1. Cmax of INCB099280
2. tmax of INCB099280
3. Cmin of INCB099280
4. AUC0-t of INCB099280
5. t1/2 of INCB099280
6. Lambda-z of INCB099280
7. CL/F of INCB099280
8. Vz/F of INCB099280

+81-3-3542-2511

Feb. 15, 2023

United States/Australia/Belgium/France