Advanced Solid Tumors
Conditions
Interventions
Phase 1a (dose increase) and phase 1b (dose extension):
• TGA: INCA00186 monotherapy (up to 2 years of treatment), with the option of
adding treatment with retifanlimab or INCB106385
• TGB1: INCA0018
Sponsors
Incyte Corporation
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: Participants are eligible to be included in the study only if all of the following criteria apply: 1. Ability to comprehend and willingness to sign a written ICF for the study. 2. Male or female participant aged 18 years or older inclusive at the time of signing the ICF. 3. Must be willing and able to conform to and comply with all Protocol requirements, including all scheduled visits and Protocol procedures. 4. Willingness to undergo pre- and on-treatment tumor biopsy (core or excisional). 5. Have CD8 T-cell-positive tumors based on evaluation of CD8+ T-lymphocyte presence by IHC performed on pretreatment tumor biopsy tissue. 6. ECOG performance status 0 or 1. 7. Measurable disease according to RECIST v1.1. 8. Phase 1a early dose level cohorts in each of the treatment groups only: Participants with advanced or metastatic solid tumors experiencing disease progression after treatment with available therapies, including anti-PD-(L)1 therapy (if applicable), that are known to confer clinical benefit, or who are intolerant to, or ineligible for standard treatment. Prior anti-PD-(L)1 therapy should not have been discontinued because of intolerance. 9. Participants with SCCHN: a. Participants with histologically or cytologically confirmed squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx, or larynx not amenable to local therapy with curative intent (surgery or radiation with or without chemotherapy). b. Participants should have disease progression after treatment with available therapies, including anti-PD-(L)1 therapy (alone or as part of a combination), that are known to confer clinical benefit or who are intolerant to or ineligible for standard treatment. Prior anti-PD-(L)1 therapy should not have been discontinued because of intolerance. 10. Participants with specified GI malignancies: Histologically or cytologically confirmed advanced or metastatic CRC, gastric/GEJ cancer, HCC, PDAC, or SCAC. a. Participants should have disease progression after treatment with available therapies, including anti-PD-(L)1 therapy (if applicable), that are known to confer clinical benefit or who are intolerant to or ineligible for standard treatment. Prior anti-PD-(L)1 therapy should not have been discontinued because of intolerance. 11. For participants to be enrolled in cohorts including INCB106385: The ability to swallow oral medication. 12. 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 (with at least 99% certainty) and refrain from donating sperm from screening through 190 days after the last dose of study treatment. Permitted methods that are at least 99% effective in preventing pregnancy should be communicated to the participants and their understanding confirmed. b. Female participants who are WOCBP must have a negative pregnancy test at screening (serum test) and before the first dose of Day 1 (urine test) and must agree to take appropriate precautions to avoid pregnancy (with at least 99% certainty) and refrain from donating oocytes from screening through 190 days after the last dose of study treatment. Permitted methods that are at least 99% effective in preventing pregnancy should be
Exclusion criteria
Exclusion criteria: Participants are excluded from the study if any of the following criteria apply: 1. Clinically significant cardiac disease, unstable angina, acute myocardial infarction within 6 months of Cycle 1 Day 1, and New York Heart Association Class III or IV congestive heart failure. 2. History or presence of an ECG abnormality that, in the investigator's opinion, is clinically meaningful. For participants to be enrolled in cohorts including INCB106385, screening QTcF interval > 450 milliseconds (ms) is excluded; in the event that a single QTc is > 450 ms, the participant may enroll if the average QTc for the 3 ECGs is 10 mg daily of prednisone or equivalent) or any other form of immunosuppressive therapy within 7 days before the first dose of study treatment. Use of short courses of steroids for procedure prophylaxis, inhaled or topical steroids, or systemic corticosteroids 1 year after treatment with curative intent. 7. Participants with exclusionary laboratory values at screening (see protocol) 8. Has not recovered to <= Grade 1 from toxic effects of prior therapy (including prior immunotherapy) and/or complications from prior surgical intervention before starting study treatment. 9. Evidence of interstitial lung disease, history of interstitial lung disease, or active noninfectious pneumonitis. 10. Immune-related toxicity during prior immune therapy for which permanent discontinuation of therapy is recommended (per product label or consensus guidelines), OR any immune-related toxicity requiring intensive or prolonged immunosuppression to manage (with the exception of endocrinopathy that is well-controlled on replacement hormones). 11. Prior treatment with any adenosine pathway targeting drugs (eg, A2A receptor and/or A2B receptor antagonists, anti-CD38, anti-CD39, anti-CD-73/CD73 antagonists). 12. Any prior chemotherapy, biological therapy, or targeted therapy to treat the participant's disease within 5 half-lives or 28 days (whichever is shorter) before the first dose of study treatment. 13. Any prior radiation therapy within 28 days before the first dose of study treatment. 14. Undergoing treatment with another investigational medication or having been treated with an investigational medication within 5 halflives or 28 days
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| * Dose Limiting Toxicities * Adverse Events (AEs), assessed by physical examinations, evaluating changes in vital signs and ECGs, and through clinical laboratory blood sample evaluations. * Impact on study treatment, assessed by treatment interruptions, dose reductions, and withdrawal of study treatment due to AEs. | — |
Secondary
| Measure | Time frame |
|---|---|
| * PK parameters for INCA000186 including Cmax, tmax, Ctau, AUC, CL, Vz, and t* as deemed appropriate. * Blockade of CD73 enzymatic activity. * Objective response: CR or PR, as determined by investigator by radiographic disease assessment according to RECIST v1.1. * Disease control: CR, PR, or SD as determined by investigator by radiographic disease assessment according to RECIST v1.1. * Duration of response: time from earliest date of disease response (CR or PR) until earliest date of disease progression as determined by investigator by radiographic disease assessment according to RECIST v1.1, or death due to any cause, if occurring sooner than progression. | — |
Countries
Netherlands
Outcome results
None listed