Head and Neck Cancer
Conditions
Keywords
squamous cell carcinoma of the head and neck (SCCHN), INCAGN02385, INCAGN02390, Retifanlimab, IgG1κ monoclonal antibody, LAG-3, TIM-3, PD-1, PD-L1
Brief summary
The purpose of this study is to evaluate the safety and efficacy of the combination of retifanlimab plus INCAGN02385 and retifanlimab plus INCAGN02385 and INCAGN02390 compared with retifanlimab alone as first-line treatment in PD-L1-positive and systemic therapy-naive recurrent/metastatic (R/M) squamous cell carcinoma of the head and neck (SCCHN).
Interventions
DRUGRetifanlimab
Retifanlimab 500mg will be administered intravenously every 4 weeks.
DRUGINCAGN02385
INCAGN02385 350mg will be administered intravenously every 2 weeks.
DRUGINCAGN02390
INCAGN02390 400 mg will be administered intravenously every 2 weeks.
DRUGPlacebo
Placebo will be administered intravenously.
Sponsors
Incyte Biosciences International Sàrl
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Intervention model description
Patients will be randomized to 1 of 3 treatment groups.
Eligibility
Sex/Gender
ALL
Age
18 Years to 99 Years
Healthy volunteers
No
Inclusion criteria
* Histologically or cytologically confirmed R/M SCCHN that is not amenable to therapy with curative intent. Participants who refuse potentially curative salvage surgery for recurrent disease are ineligible. * Eligible primary tumor locations are oropharynx, oral cavity, hypopharynx, and larynx. * Participants must not have received prior systemic therapy for R/M SCCHN. * PD-L1 positive tumor status defined by CPS ≥ 1% per central laboratory determination. * For participants with primary oropharyngeal tumors, documentation of HPV p16 status based on local institutional standard is required. HPV p16 status is not required for other eligible SCCHN primary tumor sites. * Participant must have at least 1 measurable tumor lesion per RECIST v1.1. * Availability of archival tissue for biomarker analysis from a core or excisional biopsy or willingness to undergo a fresh biopsy. * ECOG performance status of 0 or 1. * Willingness to avoid pregnancy or fathering children.
Exclusion criteria
* Progressive or recurrent disease within 6 months of the last dose of systemic treatment for locally advanced SCCHN. Prior PD-(L)1, LAG-3, or TIM-3 directed therapy, or any other checkpoint inhibitor therapy, for SCCHN or any other malignancy. * Treatment with anticancer therapies or participation in another interventional clinical study within 21 days before the first administration of study treatment. * Presence of tumors that invade major blood vessels, as shown unequivocally by imaging, and with active bleeding. * Participants with primary tumors of the nasopharynx, sinonasal cavity, or salivary and are excluded. * Less than 3-month life expectancy. * Participant has not recovered to ≤ Grade 1 or baseline from residual toxicities of prior therapy. * Participant has not recovered adequately from toxicities and/or complications from surgical intervention before starting study treatment. * 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. * 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progeression-free Survival (PFS) | up to 738 days | PFS was defined as the time from the date of randomization to the date of the first documented progression, as determined by investigator assessment per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1), or death due to any cause, whichever occurred first. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response | up to approximately 44 months | Objective response was defined as having a complete response (CR) or partial response (PR), determined based on investigator assessment per RECIST v1.1, recorded post-baseline before and including the first progressive disease, and before new anticancer therapy. CR: disappearance of all target and non-target lesions and no appearance of any new lesions. Any pathological lymph nodes (whether target or non-target) must have a reduction in the short axis to \<10 millimeters (mm). PR: complete disappearance or at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference the baseline sum diameters, no new lesions, and no progression of non-target lesions. |
| Duration of Response (DOR) | up to approximately 44 months | DOR was defined as the time from earliest date of disease response (CR or PR) until the 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 | up to approximately 44 months | Disease control was defined as having CR, PR, or stable disease (SD) as best response on or after Day 180, based on investigator assessment per RECIST v1.1. CR: disappearance of all target and non-target lesions and no appearance of any new lesions. Any pathological lymph nodes (whether target or non-target) must have a reduction in the short axis to \<10 mm. PR: complete disappearance or at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference the baseline sum diameters, no new lesions, and no progression of non-target lesions. PD: progression of a target or non-target lesion or presence of a new lesion. SD: no change in target lesions to qualify for CR, PR, or PD. |
| Overall Survival | up to approximately 44 months | Overall survival was defined as the time from the date of randomization to the date of death due to any cause. |
| Number of Participants With Treatment-emergent Adverse Events (TEAEs) | up to approximately 44 months | Adverse events (AEs) were defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not it was considered drug related. An AE could therefore be any unfavorable or unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of study treatment. A TEAE was defined as any AE either reported for the first time or the worsening of a pre-existing event after the first dose of study drug and within 90 days of the last administration of study drug. |
| Number of Participants With TEAEs Leading to Treatment Interruption, Dose Delay, and Withdrawal of Study Treatment | up to approximately 44 months | AEs were defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not it was considered drug related. An AE could therefore be any unfavorable or unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of study treatment. A TEAE was defined as any AE either reported for the first time or the worsening of a pre-existing event after the first dose of study drug and within 90 days of the last administration of study drug. |
Countries
Belgium, Canada, France, Georgia, Germany, Greece, Italy, Netherlands, Poland, Portugal, South Korea, Spain, Taiwan, United States
Participant flow
Pre-assignment details
This study was conducted at 49 sites in Canada, Spain, France, Georgia, Greece, Italy, South Korea, Portugal, Taiwan, and the United States. Data collected through 28 January 2025 have been reported.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 64.19 years STANDARD_DEVIATION 9.459 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 57 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 9 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 17 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 3 Participants |
| Race (NIH/OMB) White | 114 Participants |
| Sex: Female, Male Female | 29 Participants |
| Sex: Female, Male Male | 46 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 22 / 58 | 23 / 60 | 28 / 57 |
| other Total, other adverse events | 52 / 58 | 51 / 60 | 51 / 57 |
| serious Total, serious adverse events | 24 / 58 | 20 / 60 | 27 / 57 |
Outcome results
None listed