E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Metastatic Merkel cell carcinoma |
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E.1.1.1 | Medical condition in easily understood language |
Metastatic Merkel cell carcinoma |
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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 | 21.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10064025 |
E.1.2 | Term | Merkel cell carcinoma |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To determine the efficacy of INCMGA00012 in terms of the ORR in chemotherapy-naive participants with metastatic Merkel Cell carcinoma (MCC). |
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E.2.2 | Secondary objectives of the trial |
-To determine the DOR, DCR, PFS, and OS in the chemotherapy-naive population with metastatic MCC treated with INCMGA00012. -To evaluate the safety of INCMGA00012 in participants with advanced/metastatic MCC. -To determine the PK of INCMGA00012 administered to participants with metastatic MCC. |
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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. Signed informed consent. 2. Men and women, aged 18 or older (or as applicable per local country requirements). 3. Diagnosis of MCC with distant metastatic disease or recurrent, advanced locoregional disease not amenable to surgery or radiation. 4. ECOG performance status of 0 to 1. 5. Measurable disease according to RECIST v1.1.Tumor lesions that are located in a previously irradiated area or in an area subjected to other locoregional therapy should only be selected as target lesions if progression has been demonstrated in such lesions. 6. Availability of tumor tissue (fresh or archival) for central pathology review. 7. Willingness to avoid pregnancy or fathering children based on the criteria below. a. Men must agree to take appropriate precautions to avoid fathering children (with at least 99% certainty) from screening through 6 months after the last dose of study treatment and must refrain from donating sperm during this period. Permitted methods that are at least 99% effective in preventing pregnancy should be communicated to the participants and their understanding confirmed. b. Women of childbearing potential must have a negative serum pregnancy test at screening and before the first dose on Day 1 and must agree to take appropriate precautions to avoid pregnancy (with at least 99% certainty) from screening through safety follow-up. Permitted methods that are at least 99% effective in preventing pregnancy should be communicated to the participants and their understanding confirmed. c. Women of nonchildbearing potential (ie, surgically sterile with a hysterectomy and/or bilateral oophorectomy OR ≥ 12 months of amenorrhea and at least 50 years of age) are eligible. |
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E.4 | Principal exclusion criteria |
Participants are excluded from the study if any of the following criteria apply: 1. Prior systemic therapy for MCC, including chemotherapy and prior PD-1– or PD-L1–directed therapy. 2. Treatment with anticancer drugs or participation in another interventional clinical study within 21 days before the first administration of study drug. 3. Participant has not recovered to ≤ Grade 1 or baseline from toxic effects of prior therapy (with the exceptions for anemia not requiring transfusion support and any grade of alopecia) and/or complications from prior surgical intervention within 7 days before starting study treatment. 4. Radiation therapy administered within 2 weeks of first dose of study treatment or radiation therapy to the thoracic region that is > 30 Gy within 6 months of the first dose of study treatment. 5. Known CNS metastases and/or carcinomatous meningitis 6. Any 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. 7. Participants with laboratory values at screening as defined in protocol. 8. Evidence of interstitial lung disease or active, noninfectious pneumonitis. 9. 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, uncontrolled ≥ 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. 10. Active autoimmune disease requiring systemic immunosuppression in excess of physiologic maintenance doses of corticosteroids. 11. Chronic or current active infectious disease requiring systemic antibiotics, antifungal, or antiviral treatment. 12. Known active hepatitis A, B, or C or active infections requiring systemic antibiotics. 13. Has received a live vaccine within 9028 days of planned start of study therapy. Note: Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, chicken pox/zoster, yellow fever, rabies, Bacillus Calmette–Guérin, 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. 14. Current use of prohibited medication as described in Section 6.6.2. 15. Known hypersensitivity to another monoclonal antibody, which cannot be controlled with standard measures (eg, antihistamines and corticosteroids). 16. Participant lacks the ability or is unlikely, in the opinion of the investigator, to comply with the Protocol requirements. 17. Participant who is pregnant or breastfeeding 18. Any condition that would, in the investigator's judgment, interfere with full participation in the study, including administration of study drug/treatment and attending required study visits; pose a significant risk to the participant; or interfere with interpretation of study data. 19. History of organ transplant, including allogeneic stem cell transplantation. 20. Known allergy or hypersensitivity to any component of the study drug formulation. 21. 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. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint of the study is ORR in the chemotherapy-naive population, defined as the proportion of participants with an objective response (CR or PR), according to RECIST v1.1 as determined by an Independent Review Committee (ICR). The primary analysis of ORR will be based on the chemotherapy-naive subset of the full analysis set |
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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) |
The ORR, DOR, DCR, PFS, OS in the full study population, comprised of chemotherapy-naive and chemotherapy-refractory participants, will be evaluated as secondary endpoints. |
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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 | 8 |
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 |
Switzerland |
Canada |
United Kingdom |
United States |
Czechia |
France |
Germany |
Hungary |
Italy |
Poland |
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 | 4 |
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 | 4 |
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 |