| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| In participants with PD-L1–positive and systemic therapy–naive R/M SCCHN. |
|
| E.1.1.1 | Medical condition in easily understood language |
| In participants with biomarker positive and untreated advanced head and neck cancer |
|
| 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 | PT |
| E.1.2 | Classification code | 10071540 |
| E.1.2 | Term | Head and neck cancer metastatic |
| E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
| 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 efficacy of the combinations of retifanlimab + INCAGN02385 (TG2) and retifanlimab + INCAGN02385 + INCAGN02390 (TG3) compared with retifanlimab alone (TG1) in the overall study population. |
|
| E.2.2 | Secondary objectives of the trial |
To assess disease response per RECIST v1.1 in TG2 and TG3 compared with TG1.
To determine the OS of TG2 and TG3 compared with TG1.
To determine the safety of TG2 and TG3 compared with TG1. |
|
| 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.Age 18 years or older (or as applicable per local country requirements), inclusive at the time of signing the ICF.
3.Histologically or cytologically confirmed R/M SCCHN that is not amenable to therapy with curative intent (surgery and/or radiation therapy with or without chemotherapy). Participants who refuse potentially curative salvage surgery for recurrent disease are ineligible.
a.Eligible primary tumor locations are oropharynx, oral cavity, hypopharynx, and larynx.
b.Participants with primary tumors of the nasopharynx, sinonasal cavity, or salivary gland are excluded.
c.Participants must not have received prior systemic therapy for R/M SCCHN.
4.PD-L1 positive tumor status defined by CPS ≥ 1% per central laboratory determination.
5.For participants with primary oropharyngeal tumors, documentation of HPV p16 status (positive or negative) based on local institutional standard is required. HPV p16 status is not required for other eligible SCCHN primary tumor sites.
6.Participant must have at least 1 measurable tumor lesion per RECIST v1.1.
7.Availability of archival tissue for biomarker analysis from a core or excisional biopsy or willingness to undergo a fresh biopsy.
8.ECOG performance status of 0 or 1.
9.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 from screening through 180 days after the last dose of study treatment and must refrain from donating sperm during this period.
b.Female participants who are WOCBP must have a negative serum pregnancy test at screening and a negative urine pregnancy test before the first dose on Day 1 and must agree to take appropriate precautions to avoid pregnancy from screening through 180 days after the last dose of study treatment and must refrain from donating oocytes during this period.
c.Female participants not considered to be of childbearing potential |
|
| E.4 | Principal exclusion criteria |
1.Progressive or recurrent disease within 6 months of the last dose of systemic treatment for locally advanced SCCHN.
2.Prior PD-(L)1, LAG-3, or TIM-3 directed therapy, or any other checkpoint inhibitor therapy, for SCCHN (in any disease setting) or any other malignancy.
3.Treatment with anticancer therapies or participation in another interventional clinical study within 21 days before the first administration of study treatment
4.Presence of tumors that invade major blood vessels, as shown unequivocally by imaging, and with active bleeding.
5.Less than 3-month life expectancy (based on investigator judgement).
6.Participant has not recovered to ≤ Grade 1 or baseline from residual toxicities of prior therapy (with exceptions for anemia not requiring transfusion support, fatigue, or any grade of alopecia).
7.Participant has not recovered adequately from toxicities and/or complications from surgical intervention before starting study treatment.
8.Palliative radiation therapy administered within 1 week before the first dose of study treatment or radiation therapy in the thoracic region that is > 30 Gy within 6 months before the first dose of study treatment.
9.Known active CNS metastases and/or carcinomatous meningitis. Participants will be excluded if it has been < 4 weeks since radiation therapy was delivered to the CNS.
10.Participants with laboratory values at screening as defined
11.Has known active HBV or HCV, defined as follows (testing must be performed to determine eligibility):
a.Active HBV is defined as a known positive HBsAg result and positive total anti-HBc results.
b.Active HCV is defined as a positive HCV antibody result and quantitative HCV-RNA results greater than the lower limits of detection of the assay.
12.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 antiretroviral therapy that is not a potential risk for a drug-drug interaction with the assigned study drug.
13. Any known additional malignancy that is progressing or requires active treatment, or history of other malignancy within 3 years of the first dose of study treatment 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.
14.Has active autoimmune disease requiring systemic immunosuppression with corticosteroids (> 10 mg/day of prednisone or equivalent) or immunosuppressive drugs within 2 years before the first dose of study treatment.
15.Is on chronic systemic steroids (> 10 mg/day of prednisone or equivalent).
16.Active infections requiring systemic antibiotics or antifungal or antiviral treatment (within 14 days before first dose of study treatment).
17.Evidence of interstitial lung disease or history of interstitial lung disease, or active, noninfectious pneumonitis.
18.History of organ transplant, including allogeneic stem cell transplantation.
19.Receiving probiotics as of the first dose of study treatment.
20.History or presence of an abnormal ECG that, in the investigator's opinion, is clinically meaningful. Screening QTc interval > 460 milliseconds is excluded
21.Has had a significant cardiac event within 6 months before the first dose of study treatment
22.Has received a live vaccine within 30 days of planned start of study treatment.
23.Known hypersensitivity to another monoclonal antibody that cannot be controlled with standard measures
24.Known allergy or hypersensitivity to any component of either retifanlimab, INCAGN02385, or INCAGN02390 study drug formulation (including excipients and additives).
25.Women who are pregnant or breastfeeding.
26.Any condition that would, in the investigator's judgment, interfere with full participation in the study, including administration of study treatment and attending required study visits; pose a significant risk to the participant; or interfere with interpretation of study data.
|
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| PFS, defined as the interval between the date of randomization and the earliest date of disease progression, based on investigator assessment per RECIST v1.1, or death due to any cause. |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| Safety and endpoint assessments will be performed throughout the trial |
|
| E.5.2 | Secondary end point(s) |
•Objective response, defined as having a CR or PR, determined based on investigator assessment per RECIST v1.1.
•DOR, defined as the time from earliest date of disease response (CR or PR) until earliest date of disease progression, based on investigator assessment per RECIST v1.1, or death from any cause if occurring sooner than progression.
•Disease control, defined as having CR, PR, or SD (≥ 6 months) as best response, based on investigator assessment per RECIST v1.1.
OS, defined as the interval between the date of randomization until death due to any cause.
•AEs, assessed in body systems with symptoms, through physical examinations, 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.
|
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
| Safety and endpoint assessments will be performed throughout the trial |
|
| 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 | Yes |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | No |
| E.6.7 | Pharmacodynamic | No |
| 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 | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| 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 | Yes |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 3 |
| 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 | No |
| 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 |
| Australia |
| Korea, Republic of |
| United States |
| Netherlands |
| Spain |
| Germany |
| Italy |
| Belgium |
| Georgia |
| Portugal |
|
| 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
|
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 1 |
| E.8.9.1 | In the Member State concerned months | 2 |
| E.8.9.1 | In the Member State concerned days | 1 |
| E.8.9.2 | In all countries concerned by the trial years | 1 |
| E.8.9.2 | In all countries concerned by the trial months | 2 |
| E.8.9.2 | In all countries concerned by the trial days | 1 |
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