Squamous Cell Carcinoma of Anal Canal
Conditions
Keywords
Squamous carcinoma of the anal canal, anti-PD-1 antibody, IgG4 monoclonal antibody, INCMGA00012
Brief summary
The purpose of this study is to assess the efficacy of INCMGA00012 in participants with locally advanced or metastatic squamous carcinoma of the anal canal (SCAC) who have progressed after platinum-based chemotherapy.
Interventions
DRUGRetifanlimab
Retifanlimab 500 milligrams (mg) intravenously every 4 weeks (Q4W).
Sponsors
Incyte Corporation
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Ability to comprehend and willingness to sign a written informed consent form. * Confirmed diagnosis of locally advanced or metastatic SCAC. * Must have received (or been intolerant to or ineligible for) at least 1 prior line of platinum-based chemotherapy and received no more than 2 prior systemic treatments. * Must have measurable disease by RECIST v1.1. * Eastern Cooperative Oncology Group performance status of 0 to 1. * If HIV-positive, then all of the following criteria must also be met: CD4+ count ≥ 300/μL, undetectable viral load, and receiving highly active antiretroviral therapy.
Exclusion criteria
* Receipt of anticancer therapy or participation in another interventional clinical study within 21 days before the first administration of study drug; 6 weeks for mitomycin C. * Radiotherapy within 14 days of first dose of study treatment with the following caveats: 28 days for pelvic radiotherapy, 6 months for thoracic region radiotherapy that is \> 30 Gy. * Prior treatment with programmed cell death protein 1 (PD-1) or programmed cell death ligand protein 1 (PD-L1)-directed therapy. * Active autoimmune disease requiring systemic immunosuppression. * Known central nervous system (CNS) metastases and/or carcinomatous meningitis. * Known active hepatitis infection. * Active infections requiring systemic therapy. * Is pregnant or breastfeeding or is expecting to conceive or father children within the projected duration of the study, from screening through 6 months after the last dose of study drug.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) | Cycle 1 Day 1, and every 4 weeks throughout the study, up to approximately 24 months | ORR was defined as the percentage of participants with a best overall response of complete response (CR) or partial response (PR), per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 (v1.1), as assessed by independent central radiographic (ICR) review, at any post-Baseline visit until new anti-cancer therapy or first Progressive Disease. 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Disease Control Rate (DCR) | Cycle 1 Day 1, and every 4 weeks throughout the study, up to approximately 24 months | DCR was defined as the percentage of participants with a confirmed overall response of CR, PR, or stable disease (SD), per RECIST v1.1, at any post-baseline visit until the first progressive disease (PD) or new anti-cancer 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 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. |
| Progression-free Survival (PFS) | up to 16.8 months | According to RECIST 1.1, PFS was defined as the length of time from the initial infusion of study drug until the earliest date of disease progression, as determined by ICR, or death due to any cause, if occurring sooner than progression. |
| Overall Survival | up to 28.2 months | Overall survival was defined as the time in months between the first dose date (Day 1) and the date of death due to any cause. |
| Number of Participants With Treatment-emergent Adverse Events (TEAEs) | up to 913 days | An adverse event (AE) was defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug-related. An AE could have been any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of the study drug. 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 retifanlimab and within 90 days of the last administration of retifanlimab. |
| Duration of Response (DOR) | up to 18.2 months | DOR was defined as the time from an initial objective response (CR or PR) per RECIST v1.1 until the first observation of documented disease progression (PD), as determined by ICR, or death due to any cause. 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. |
| Tmax of Retifanlimab | pre-infusion on Day 1 of Cycles 1, 2, 4, 6, and 7; 10 minutes and 4 hours post-infusion on Day 1 of Cycles 1 and 6 | tmax was defined as the time to the maximum concentration. |
| Cmin of Retifanlimab | pre-infusion on Day 1 of Cycles 1, 2, 4, 6, and 7; 10 minutes and 4 hours post-infusion on Day 1 of Cycles 1 and 6 | Cmin was defined as the minimum observed plasma concentration over the dose interval. |
| AUC0-t of Retifanlimab | pre-infusion on Day 1 of Cycles 1, 2, 4, 6, and 7; 10 minutes and 4 hours post-infusion on Day 1 of Cycles 1 and 6 | AUC0-t was defined as the area under the plasma concentration-time curve from time = 0 to the last measurable concentration at time = t. |
| Cmax of Retifanlimab | pre-infusion on Day 1 of Cycles 1, 2, 4, 6, and 7; 10 minutes and 4 hours post-infusion on Day 1 of Cycles 1 and 6 | Cmax was defined as the maximum observed plasma concentration. |
Countries
Belgium, Denmark, France, Germany, Italy, Norway, Spain, United Kingdom, United States
Participant flow
Recruitment details
This study was conducted at 40 study centers: 32 in France, 19 in the United Kingdom, 10 in Italy, 10 in Spain, 7 in Denmark, 6 in the United States, 4 in Norway, 4 in Belgium, and 2 in Germany.
Pre-assignment details
A total of 94 participants with locally advanced or metastatic squamous carcinoma of the anal canal were enrolled in the study and treated with retifanlimab.
Participants by arm
| Arm | Count |
|---|---|
| Retifanlimab 500 mg Participants received retifanlimab 500 milligrams (mg) intravenously every 4 weeks (Q4W). | 94 |
| Total | 94 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Death | 70 |
| Overall Study | Lost to Follow-up | 7 |
Baseline characteristics
| Characteristic | Retifanlimab 500 mg |
|---|---|
| Age, Continuous | 62.1 Years STANDARD_DEVIATION 11.44 |
| Race/Ethnicity, Customized Black/African-American | 1 Participants |
| Race/Ethnicity, Customized Captured as Other | 4 Participants |
| Race/Ethnicity, Customized Hispanic or Latino | 4 Participants |
| Race/Ethnicity, Customized Missing | 6 Participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 49 Participants |
| Race/Ethnicity, Customized Not Reported | 33 Participants |
| Race/Ethnicity, Customized Unknown | 4 Participants |
| Race/Ethnicity, Customized White/Caucasian | 72 Participants |
| Sex: Female, Male Female | 61 Participants |
| Sex: Female, Male Male | 33 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 60 / 94 |
| other Total, other adverse events | 79 / 94 |
| serious Total, serious adverse events | 50 / 94 |
Outcome results
Primary
Objective Response Rate (ORR)
ORR was defined as the percentage of participants with a best overall response of complete response (CR) or partial response (PR), per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 (v1.1), as assessed by independent central radiographic (ICR) review, at any post-Baseline visit until new anti-cancer therapy or first Progressive Disease. 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.
Time frame: Cycle 1 Day 1, and every 4 weeks throughout the study, up to approximately 24 months
Population: Full Analysis Set: all participants enrolled in the study who received at least 1 dose of study drug
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Retifanlimab 500 mg | Objective Response Rate (ORR) | 13.8 percentage of participants |
Secondary
AUC0-t of Retifanlimab
AUC0-t was defined as the area under the plasma concentration-time curve from time = 0 to the last measurable concentration at time = t.
Time frame: pre-infusion on Day 1 of Cycles 1, 2, 4, 6, and 7; 10 minutes and 4 hours post-infusion on Day 1 of Cycles 1 and 6
Population: PK Evaluable Population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Retifanlimab 500 mg | AUC0-t of Retifanlimab | 1950 day*mg/L | Standard Deviation 594 |
Secondary
Cmax of Retifanlimab
Cmax was defined as the maximum observed plasma concentration.
Time frame: pre-infusion on Day 1 of Cycles 1, 2, 4, 6, and 7; 10 minutes and 4 hours post-infusion on Day 1 of Cycles 1 and 6
Population: Pharmacokinetic (PK) Evaluable Population: all participants who received at least 1 dose of study drug and provided a Baseline and at least 1 postdose serum sample (1 PK measurement)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Retifanlimab 500 mg | Cmax of Retifanlimab | 151 milligrams per Liter (mg/L) | Standard Deviation 27.6 |
Secondary
Cmin of Retifanlimab
Cmin was defined as the minimum observed plasma concentration over the dose interval.
Time frame: pre-infusion on Day 1 of Cycles 1, 2, 4, 6, and 7; 10 minutes and 4 hours post-infusion on Day 1 of Cycles 1 and 6
Population: PK Evaluable Population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Retifanlimab 500 mg | Cmin of Retifanlimab | 22.4 mg/L | Standard Deviation 7.87 |
Secondary
Disease Control Rate (DCR)
DCR was defined as the percentage of participants with a confirmed overall response of CR, PR, or stable disease (SD), per RECIST v1.1, at any post-baseline visit until the first progressive disease (PD) or new anti-cancer 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 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.
Time frame: Cycle 1 Day 1, and every 4 weeks throughout the study, up to approximately 24 months
Population: Full Analysis Set. Confidence intervals were calculated based on the exact method for binomial distributions.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Retifanlimab 500 mg | Disease Control Rate (DCR) | 48.9 percentage of participants |
Secondary
Duration of Response (DOR)
DOR was defined as the time from an initial objective response (CR or PR) per RECIST v1.1 until the first observation of documented disease progression (PD), as determined by ICR, or death due to any cause. 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.
Time frame: up to 18.2 months
Population: Full Analysis Set. All participants with confirmed tumor responses (CR or PR) by ICR according to RECIST v1.1 were analyzed. The 95% confidence interval was calculated using the Brookmeyer and Crowley's method and Klein and Moeschberger's method with log-log transformation.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Retifanlimab 500 mg | Duration of Response (DOR) | 9.5 months |
Secondary
Number of Participants With Treatment-emergent Adverse Events (TEAEs)
An adverse event (AE) was defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug-related. An AE could have been any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of the study drug. 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 retifanlimab and within 90 days of the last administration of retifanlimab.
Time frame: up to 913 days
Population: Safety Evaluable Population: all enrolled participants who received at least 1 dose of study drug
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Retifanlimab 500 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | 90 Participants |
Secondary
Overall Survival
Overall survival was defined as the time in months between the first dose date (Day 1) and the date of death due to any cause.
Time frame: up to 28.2 months
Population: Full Analysis Set. Median survival time was estimated using the Kaplan-Meier method. The confidence interval for median survival time was calculated using the method of Brookmeyer and Crowley.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Retifanlimab 500 mg | Overall Survival | 13.4 months |
Secondary
Progression-free Survival (PFS)
According to RECIST 1.1, PFS was defined as the length of time from the initial infusion of study drug until the earliest date of disease progression, as determined by ICR, or death due to any cause, if occurring sooner than progression.
Time frame: up to 16.8 months
Population: Full Analysis Set. Median PFS time was estimated using the Kaplan-Meier method. The confidence interval for median PFS time was calculated using the method of Brookmeyer and Crowley.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Retifanlimab 500 mg | Progression-free Survival (PFS) | 2.3 months |
Secondary
Tmax of Retifanlimab
tmax was defined as the time to the maximum concentration.
Time frame: pre-infusion on Day 1 of Cycles 1, 2, 4, 6, and 7; 10 minutes and 4 hours post-infusion on Day 1 of Cycles 1 and 6
Population: PK Evaluable Population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Retifanlimab 500 mg | Tmax of Retifanlimab | 1.20 hours | Standard Deviation 0.305 |