E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Immune Checkpoint Inhibitor–Naïve Selected Solid Tumors |
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E.1.1.1 | Medical condition in easily understood language |
Immune Checkpoint Inhibitor–Naïve Selected Solid Tumors |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10049280 |
E.1.2 | Term | Solid tumour |
E.1.2 | System Organ Class | 100000004864 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10065143 |
E.1.2 | Term | Malignant solid tumour |
E.1.2 | System Organ Class | 100000004864 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To determine the ORR of participants treated with INCB086550. |
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E.2.2 | Secondary objectives of the trial |
To determine the efficacy of INCB086550 in participants with advanced solid tumors in respect to DCR. To determine the efficacy of INCB086550 in participants with advanced solid tumors in respect to DOR. To evaluate the safety of INCB086550 in participants with advanced solid tumors. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Ability to comprehend and willingness to sign a written ICF for the study. 2. Men and women 18 years of age or older. 3. Measurable disease per RECIST v1.1. 4. ECOG performance status of 0 to 1 for all tumor types. Urothelial carcinoma allows ECOG of 0 to 2. 5. Histologically or cytologically confirmed disease-specific diagnosis as follows: a. Treatment-naïve, stage IV NSCLC (AJCC v8) in participants whose tumors express PD-L1 TPS ≥ 50% using the Dako PD-L1 IHC 22C3 assay and who have no known activating genomic aberrations that require targeted therapy (eg, EGFR, ALK, ROS, BRAF). b. Locally advanced, and unresectable or metastatic UC of the renal pelvis, ureter, bladder, or urethra (including transitional cell and mixed transitional or nontransitional cell histologies) in participants who are cisplatin-ineligible, who are immune checkpoint inhibitor–naïve, and whose tumors express high PD-L1 (CPS ≥ 10) using the Dako PD-L1 IHC 22C3 assay. c. Advanced HCC that is not amenable to curative surgery or local treatment in participants who have received at least 1 previous line of systemic therapy (ie, sorafenib or lenvatinib) or who were intolerant of sorafenib/lenvatinib treatment, have a Child-Pugh score of ≤ 6 (Child- Pugh A), and who are immune checkpoint inhibitor–naïve. Exception for HCC: Participants without access to prior systemic therapy (ie, sorafenib or lenvatinib). d. Advanced or metastatic RCC with a clear cell component with or without sarcomatoid features in participants who have received prior systemic therapy for their disease (up to 2 previous regimens of a VEGF or mTOR inhibitor) and who are immune checkpoint inhibitor–naïve. Exception for RCC: Participants without access to prior systemic therapy (ie, VEGF or mTOR inhibitors). e. Unresectable stage III or IV melanoma (excluding ocular/uveal melanoma) in participants who are immune checkpoint inhibitor–naïve. BRAF V600 mutation status must be known. Exception for melanoma: Participants may have received 1 prior line of therapy. This therapy could include previous treatment with BRAF/MEK inhibitors in participants with known BRAF V600 mutation or chemotherapy. 6. Willingness to avoid pregnancy or fathering children (CTFG 2020). 7. Participants must have radiologic documentation of disease progression after treatment with available therapies except for participants with NSCLC, who are required to be treatment-naïve. |
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E.4 | Principal exclusion criteria |
1. Prior receipt of an anti–PD-1, anti–PD-L1, or anti–PD-L2 agent, or treatment with an immune modulator (eg, CTLA-4, GITR, LAG3, TIM3, OX40, ICOS, IL2, 4-1BB, CAR-T). 2. Receipt of any anticancer therapy or participation in another interventional clinical study. 3. Radiotherapy within 14 days of first dose of study treatment (28 days for pelvic radiotherapy or 6 months for thoracic region radiotherapy that is > 30 Gy). 4. Concomitant treatment with moderate and potent CYP3A4/CYP3A5 inhibitors or inducers 5. Toxicity of 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). 6. Participant has not recovered adequately from toxicities and/or complications from surgical intervention before starting study drug. 7. Participants with laboratory values at screening as defined in the protocol. 8. Active malignancy of a type not included in the study population requiring treatment. 9. Active autoimmune disease requiring systemic immunosuppression in excess of physiologic maintenance doses of corticosteroids (> 10 mg of prednisone or equivalent). 10. Evidence of interstitial lung disease or active, noninfectious pneumonitis. 11. Untreated or known active CNS metastases and/or carcinomatous meningitis. 12. With the exception of participants with HCC, known active HAV, HBV, or HCV infection, as defined by elevated transaminases with the following serology: positivity for HAV IgM antibody, anti-HCV, anti-HBc IgG or IgM, or HBsAg (in the absence of prior immunization). Note: For participants with cleared prior HBV infection: HBV prophylaxis should be considered per investigator discretion. Monitor for HBV reactivation every 3 cycles by performing HBV viral load and HBsAg serology test. Additional viral serologic testing may be performed at the investigator's discretion. 13. Active infection requiring systemic therapy. 14. Receipt of systemic antibiotics within 28 days of first dose of study treatment. 15. Probiotic usage during screening and throughout the study treatment period. 16. Participants who are known to be HIV-positive. 17. Participants with impaired cardiac function or clinically significant cardiac disease: a. New York Heart Association Class III or IV cardiac disease, including preexisting clinically significant ventricular arrhythmia, congestive heart failure, or cardiomyopathy. b. Unstable angina pectoris ≤ 6 months before study participation. c. Acute myocardial infarction ≤ 6 months before study participation. d. Other clinically significant heart disease (ie, ≥ Grade 3 hypertension, history of labile hypertension, or poor compliance with an antihypertensive regimen) must have recovered (to baseline or ≤ Grade 1) from toxicity associated with prior treatment. 18. History or presence of an ECG finding that, in the investigator's opinion, is clinically meaningful. sponsor approval. 19. Female participant is pregnant or breastfeeding within the projected duration of the study, starting with the screening visit through the 90-day safety follow-up, or male participant is expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 100 days after the last dose of study treatment. 20. Has received a live vaccine within 90 days of the planned start of study drug. 21. Current use of a prohibited medication as described in the protocol. 22. Life expectancy < 3 months. 23. Known hypersensitivity or severe reaction to any component of study drug or formulation components. 24. History of organ transplant, including allogeneic stem cell transplantation. 25. Presence of gastrointestinal condition that may affect drug absorption. 26. 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. |
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E.5 End points |
E.5.1 | Primary end point(s) |
ORR, defined as the percentage of participants with a best overall response of CR or PR confirmed by at least 1 repeat assessment ≥ 28 days later according to RECIST v1.1 as determined by the investigator. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Safety and endpoint assessments will be performed throughout the study. |
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E.5.2 | Secondary end point(s) |
DCR, defined as the percentage of participants with a best overall response of CR or PR confirmed by at least 1 repeat assessment ≥ 28 days later, or SD for ≥ 12 weeks, by investigator assessment per RECIST v1.1. DOR, defined as the time from the earliest date of CR or PR confirmed by at least 1 repeat assessment ≥ 28 days later 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. Safety is determined by monitoring the frequency and severity of AEs, including the evaluation of laboratory tests, vital signs, and ECGs. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Endpoint assessments will be performed throughout the study. Disease assessments will be made every 8 weeks for the first 12 months and then every 12 weeks. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 1 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 10 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 30 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Korea, Republic of |
Russian Federation |
Serbia |
Taiwan |
Ukraine |
Bulgaria |
Hungary |
Romania |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 4 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |