E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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 |
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E.1.1.1 | Medical condition in easily understood language |
Adults with advanced NSCLC, UC, melanoma, or RCC |
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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 | 20.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10080083 |
E.1.2 | Term | Advanced lung cancer |
E.1.2 | System Organ Class | 100000004864 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10027481 |
E.1.2 | Term | Metastatic melanoma |
E.1.2 | System Organ Class | 100000004864 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10064467 |
E.1.2 | Term | Urothelial carcinoma |
E.1.2 | System Organ Class | 100000004864 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10038395 |
E.1.2 | Term | Renal carcinoma |
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 assess the efficacy of INCMGA00012 in terms of the ORR in tumor types of interest. |
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E.2.2 | Secondary objectives of the trial |
To determine the DOR , DCR, PFS, OS, safety, and PK of INCMGA00012
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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 (determined by the investigator) 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. |
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E.4 | Principal 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).
a. Adjuvant therapy that was completed ≥ 12 months before study entry may be acceptable but should be discussed with the medical monitor before enrolling the participant on study.
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.
c. 14 days for palliative radiation therapy.
Note: Participants must have recovered from all radiation-related toxicities, not require corticosteroids for this purpose, and not have had radiation pneumonitis.
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. Known additional malignancy that is progressing or requires active treatment, or history of other malignancy within 3 years of study entry with the exception of cured basal cell or squamous cell carcinoma of the skin, superficial bladder cancer, prostate intraepithelial neoplasm,
carcinoma in situ of the cervix, or other noninvasive or indolent malignancy, or cancers from which the participant has been disease-free for > 1 year, after treatment with curative intent.
8. Activeautoimmune disease requiring systemic immunosuppression in excess of physiologic maintenance doses of corticosteroids (> 10 mg of prednisone or equivalent).
a. Physiologic corticosteroid replacement therapy at doses > 10 mg/day of prednisone or equivalent for adrenal or pituitary insufficiency and in the absence of active autoimmune disease is permitted.
b. Participants with asthma that requires intermittent use of
bronchodilators, inhaled steroids, or local steroid injections may participate.
c. Participants using topical, ocular, intra-articular, or intranasal steroids (with minimal systemic absorption) may participate.
d. Brief courses of corticosteroids for prophylaxis (eg, contrast dye allergy) or study treatment–related standard premedication are permitted.
9. Evidence of interstitial lung disease or active noninfectious pneumonitis.
10. Known active CNS metastases and/or carcinomatous meningitis.
11. Known active HBA, 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).
15. 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.
c. Acute myocardial infarction ≤ 6 months before study participation.
d. Other clinically significant heart disease.
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 vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (eg, FluMist®) are live-attenuated vaccines and are not allowed.
18. Current use of prohibited medication as described in protocol.
19. 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.
20. History of organ transplant, including allogeneic stem cell transplantation.
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E.5 End points |
E.5.1 | 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. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | 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.
DCR, defined as the proportion of participants with either an objective response
PFS, defined as the time from the start of therapy until disease progression, as determined by investigator or death due to any cause.
OS, defined as the time from the start of therapy until death due to any cause.
Safety, determined by the number of participants, frequency, duration, and severity of AEs, laboratory tests, vital signs, and ECGs.
The PK of INCMAG00012 including Cmax, tmax, Cmin, and AUCt, will be summarized. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | Yes |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
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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 | 3 |
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 |
United States |
Austria |
France |
Hungary |
Italy |
Poland |
Romania |
Spain |
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E.8.7 | Trial has a data monitoring committee | No |
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 | 3 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |