A Phase 2 Study of INCMGA00012 (PD-1 Inhibitor) in Participants With Selected Solid Tumors (POD1UM-203)

Phase 1

Conditions: Male or female, 18 years or older with histologically or cytologically confirmed diagnosis of :a. NSCLC with high PD-L1 expression (TPS = 50%) and no EGFR, ALK, or ROS activating genomic tumor aberrations.b. advanced or metastatic UC in participants who are not eligible for cisplatin therapy and whose tumors express PD-L1 with a CPS = 10.c. unresectable or metastatic melanoma.d. advanced or metastatic RCC with clear cell component and having received no prior systemic therapy
MedDRA version: 20.1Level: LLTClassification code 10080083Term: Advanced lung cancerSystem Organ Class: 100000004864
MedDRA version: 20.0Level: LLTClassification code 10027481Term: Metastatic melanomaSystem Organ Class: 100000004864
MedDRA version: 20.0Level: LLTClassification code 10064467Term: Urothelial carcinomaSystem Organ Class: 100000004864
MedDRA version: 21.0Level: LLTClassification code 10038395Term: Renal carcinomaSystem Organ Class: 100000004864
Therapeutic area: Diseases [C] - Cancer [C04]

Registration Number: EUCTR2018-002941-12-RO

Lead Sponsor: Incyte Corporation

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Authorised-recruitment may be ongoing or finished

Sex: All

Target Recruitment: 160

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. Men and women 18 years of age or older (or as applicable per local country requirements).
3. Confirmed diagnosis of one of the following:
a. Treatment-naïve metastatic NSCLC with high PD-L1 expression (TPS = 50%) and no EGFR, ALK, or ROS activating genomic tumor aberrations.
b. Locally-advanced or metastatic UC in participants who are not eligible for cisplatin therapy and whose tumors express PD-L1 with a CPS = 10.
c. Unresectable or metastatic melanoma.
d. Locally advanced or metastatic RCC with clear cell component (with or without sarcomatoid features) and having received no prior systemic therapy
4. Measurable disease per RECIST v1.1.
5. ECOG performance status 0 to 1.
6. Willingness to avoid pregnancy or fathering children as described in the protocol.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 60
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 100

Exclusion Criteria

Participants are excluded from the study if any of the following criteria apply:
1. Receipt of anticancer therapy or participation in another interventional clinical study within 21 days before the first administration of study drug.
2. Prior treatment with PD-1 or PD-L1 directed therapy (other immunotherapies may be acceptable with prior approval from the medical monitor).
3. Radiotherapy within 14 days of first dose of study treatment with the following caveats:
a. 28 days for pelvic radiotherapy.
b. 6 months for thoracic region radiotherapy that is > 30 Gy.
4. 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). Endocrinopathy, if well-managed, is not exclusionary and should be discussed with sponsor medical monitor.
5. Participant has not recovered adequately from toxicities and/or complications from surgical intervention before starting study drug.
6. Participants with laboratory values at screening as defined in Table 7 of the protocol.
7. Active malignancy requiring treatment of a type not included in the study population.
8. Active autoimmune disease requiring systemic immunosuppression in excess of physiologic maintenance doses of corticosteroids (> 10 mg of prednisone or equivalent).
9. Evidence of interstitial lung disease or active noninfectious pneumonitis.
10. Known active CNS metastases and/or carcinomatous meningitis.
Note: Participants with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least 28 days before the first dose of study drug and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases or CNS edema, and have not required steroids for at least 14 days before the first dose of study drug.
11. 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).
12. Active infections requiring systemic therapy.
13. Participants who are known to be HIV-positive, unless all of the following criteria are met:
a. CD4+ count = 300/µL, b. Undetectable viral load , c. Receiving highly active antiretroviral therapy.
14. Known hypersensitivity to another mAb that cannot be controlled with standard measures (eg, antihistamines and corticosteroids).
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.
16. Participant is pregnant or breastfeeding.
17. Has received a live vaccine within 28 days of the planned start of study drug.
Note: Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, chicken pox/zoster, yellow fever, rabies, BCG, and typhoid vaccine. Seasonal influenza vacc

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To assess the efficacy of INCMGA00012 in terms of the ORR in tumor types of interest.;Secondary Objective: To determine the DOR , DCR, PFS, OS, safety, and PK of INCMGA00012<br><br>;Primary end point(s): ORR, defined as the percentage of participants having a CR or PR, according to RECIST v1.1 as determined by the investigator.;Timepoint(s) of evaluation of this end point: Throughout the study

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): DOR, defined as the time from an initial objective response (CR or PR) according to RECIST v1.1 until first observation of documented disease progression as determined by investigator or death due to any cause.<br>DCR, defined as the proportion of participants with either an objective response<br>PFS, defined as the time from the start of therapy until disease progression, as determined by investigator or death due to any cause.<br>OS, defined as the time from the start of therapy until death due to any cause.<br>Safety, determined by the number of participants, frequency, duration, and severity of AEs, laboratory tests, vital signs, and ECGs.<br>The PK of INCMAG00012 including Cmax, tmax, Cmin, and AUCt, will be summarized.;Timepoint(s) of evaluation of this end point: Throughout the study

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