Trial Outcomes & Findings for Efficacy of INCMGA00012 in Penile Squamous Cell Carcinoma (ORPHEUS) (NCT NCT04231981)
NCT ID: NCT04231981
Last Updated: 2025-05-29
Results Overview
The primary efficacy endpoint for the study is the ORR. The ORR is defined as the number of patients with CR and PR divided by the number of patients in the analysis set. Tumor response will be defined as best response based on local investigator's assessment according to RECIST criteria v.1.1.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
18 participants
Primary outcome timeframe
From baseline until disease progression or treatment discontinuation, up to 10.3 months
Results posted on
2025-05-29
Participant Flow
Between April 2020 and August 2021, a total of 18 male patients with locally advanced unresectable or metastatic PSqCC stage 4 (i.e. T4 or N3 or M1)presenting radiologic PD and/or chemotherapy were enrolled at 9 sites. Due there's only one arm, all the patients received INCMGA00012 until disease progression, death or discontinuation from the study.
Male patients ≥ 18 years of age. ECOG Performance Status ≤ 1. Life expectancy ≥12 weeks. Histologically-proven PSqCC. Locally advanced unresectable/metastatic stage 4 PSqCC that is not amenable to resection with curative intent (T4 or N3 or M1). - Radiological evidence of locally advanced or metastatic disease. - Adequate organ function.
Participant milestones
| Measure |
Interventional Arm
Patients will receive INCMGA00012 500 mg by intravenous infusion on Day1 of each cycle.
Retifanlimab: INCMGA00012 500 mg will be administered on Day1 of each cycle (once every four weeks), for up to 2 years.
|
|---|---|
|
Overall Study
STARTED
|
18
|
|
Overall Study
COMPLETED
|
0
|
|
Overall Study
NOT COMPLETED
|
18
|
Reasons for withdrawal
| Measure |
Interventional Arm
Patients will receive INCMGA00012 500 mg by intravenous infusion on Day1 of each cycle.
Retifanlimab: INCMGA00012 500 mg will be administered on Day1 of each cycle (once every four weeks), for up to 2 years.
|
|---|---|
|
Overall Study
Adverse Event
|
1
|
|
Overall Study
Death
|
16
|
|
Overall Study
Lost to Follow-up
|
1
|
Baseline Characteristics
Efficacy of INCMGA00012 in Penile Squamous Cell Carcinoma (ORPHEUS)
Baseline characteristics by cohort
| Measure |
Interventional Arm
n=18 Participants
Patients will receive INCMGA00012 500 mg by intravenous infusion on Day1 of each cycle.
Retifanlimab: INCMGA00012 500 mg will be administered on Day1 of each cycle (once every four weeks), for up to 2 years.
|
|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=99 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
8 Participants
n=99 Participants
|
|
Age, Categorical
>=65 years
|
10 Participants
n=99 Participants
|
|
Age, Continuous
|
66.5 years
n=99 Participants
|
|
Sex: Female, Male
Female
|
0 Participants
n=99 Participants
|
|
Sex: Female, Male
Male
|
18 Participants
n=99 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
1 Participants
n=99 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
17 Participants
n=99 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=99 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=99 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=99 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=99 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=99 Participants
|
|
Race (NIH/OMB)
White
|
18 Participants
n=99 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=99 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=99 Participants
|
|
Region of Enrollment
Italy
|
5 participants
n=99 Participants
|
|
Region of Enrollment
Spain
|
13 participants
n=99 Participants
|
PRIMARY outcome
Timeframe: From baseline until disease progression or treatment discontinuation, up to 10.3 monthsThe primary efficacy endpoint for the study is the ORR. The ORR is defined as the number of patients with CR and PR divided by the number of patients in the analysis set. Tumor response will be defined as best response based on local investigator's assessment according to RECIST criteria v.1.1.
Outcome measures
| Measure |
Interventional Arm
n=18 Participants
Patients will receive INCMGA00012 500 mg by intravenous infusion on Day1 of each cycle.
Retifanlimab: INCMGA00012 500 mg will be administered on Day1 of each cycle (once every four weeks), for up to 2 years.
|
|---|---|
|
Objective Response Rate (ORR)
Yes
|
3 Participants
|
|
Objective Response Rate (ORR)
No
|
15 Participants
|
SECONDARY outcome
Timeframe: From baseline until disease progression or treatment discontinuation, up to 10.3 monthsCBR is defined as the number of patients with CR, partial response (PR) or stable disease (SD) (for at least 12 weeks) divided by the number of patients in the analysis set.
Outcome measures
| Measure |
Interventional Arm
n=18 Participants
Patients will receive INCMGA00012 500 mg by intravenous infusion on Day1 of each cycle.
Retifanlimab: INCMGA00012 500 mg will be administered on Day1 of each cycle (once every four weeks), for up to 2 years.
|
|---|---|
|
Efficacy Determined by Clinical Benefit Rate (CBR)
Yes
|
4 Participants
|
|
Efficacy Determined by Clinical Benefit Rate (CBR)
No
|
14 Participants
|
SECONDARY outcome
Timeframe: From baseline until disease progression or treatment discontinuation, up to 10.3 monthsPFS is defined as the time from the date of the first dose of study treatment until the first documented PD based on RECIST v1.1. or death due to any cause, whichever occurs first based on local investigator's assessment according to RECIST criteria v1.1.
Outcome measures
| Measure |
Interventional Arm
n=18 Participants
Patients will receive INCMGA00012 500 mg by intravenous infusion on Day1 of each cycle.
Retifanlimab: INCMGA00012 500 mg will be administered on Day1 of each cycle (once every four weeks), for up to 2 years.
|
|---|---|
|
Efficacy Determined by Progression-free Survival (PFS)
|
2 months
Interval 1.6 to 3.3
|
SECONDARY outcome
Timeframe: Baseline up to 6 months6-months PFS rate is defined as the proportion of patients who are alive and progression-free at 6 months from the date of first dose of study treatment based on iRECIST criteria.
Outcome measures
| Measure |
Interventional Arm
n=18 Participants
Patients will receive INCMGA00012 500 mg by intravenous infusion on Day1 of each cycle.
Retifanlimab: INCMGA00012 500 mg will be administered on Day1 of each cycle (once every four weeks), for up to 2 years.
|
|---|---|
|
Efficacy Determined by 6-months PFS
|
2 Participants
|
SECONDARY outcome
Timeframe: From baseline until disease progression or treatment discontinuation, up to 10.3 monthsDoR is defined as the time from first documented CR or PR until disease progression or death from any cause, based on local investigator's assessment according to RECIST criteria v1.1.
Outcome measures
| Measure |
Interventional Arm
n=18 Participants
Patients will receive INCMGA00012 500 mg by intravenous infusion on Day1 of each cycle.
Retifanlimab: INCMGA00012 500 mg will be administered on Day1 of each cycle (once every four weeks), for up to 2 years.
|
|---|---|
|
Efficacy Determined by Duration of Response (DoR)
|
3.3 months
Interval 1.8 to 8.5
|
SECONDARY outcome
Timeframe: From baseline until disease progression or treatment discontinuation, up to 10.3 monthsOS is defined as the time from the date of first dose of study treatment until death by any cause or the last date the patient was known to be alive.
Outcome measures
| Measure |
Interventional Arm
n=18 Participants
Patients will receive INCMGA00012 500 mg by intravenous infusion on Day1 of each cycle.
Retifanlimab: INCMGA00012 500 mg will be administered on Day1 of each cycle (once every four weeks), for up to 2 years.
|
|---|---|
|
Efficacy Determined by Overall Survival (OS)
|
17 Participants
|
SECONDARY outcome
Timeframe: From baseline until disease progression or treatment discontinuation, up to 10.3 monthsMaximum tumor shrinkage is defined as the percentage of tumor shrinkage from baseline (obtained from the sum of largest diameters of the target lesions), based on local investigator's assessment according to RECIST criteria v1.1.
Outcome measures
| Measure |
Interventional Arm
n=18 Participants
Patients will receive INCMGA00012 500 mg by intravenous infusion on Day1 of each cycle.
Retifanlimab: INCMGA00012 500 mg will be administered on Day1 of each cycle (once every four weeks), for up to 2 years.
|
|---|---|
|
Efficacy Determined by Maximum Tumor Shrinkage
|
15.9 percentage of change from baseline
Standard Deviation 49.1
|
SECONDARY outcome
Timeframe: From baseline until disease progression or treatment discontinuation, up to 10.3 monthsNumber of patients with treatment-related AEs (Grade 3 and 4 AEs and serious adverse events \[SAEs\]) by using the National Cancer Institute (NCI)-Common Terminology Criteria for Adverse Events (CTCAE) v.5.0.
Outcome measures
| Measure |
Interventional Arm
n=18 Participants
Patients will receive INCMGA00012 500 mg by intravenous infusion on Day1 of each cycle.
Retifanlimab: INCMGA00012 500 mg will be administered on Day1 of each cycle (once every four weeks), for up to 2 years.
|
|---|---|
|
Safety Adverse Events (AEs)
Related AEs
|
5 Participants
|
|
Safety Adverse Events (AEs)
Related SAEs
|
0 Participants
|
|
Safety Adverse Events (AEs)
Related Grade 3 or 4 AEs
|
1 Participants
|
|
Safety Adverse Events (AEs)
Safe patients from related AEs
|
12 Participants
|
Adverse Events
Interventional Arm
Serious events: 5 serious events
Other events: 5 other events
Deaths: 16 deaths
Serious adverse events
| Measure |
Interventional Arm
n=18 participants at risk
Patients will receive INCMGA00012 500 mg by intravenous infusion on Day1 of each cycle.
Retifanlimab: INCMGA00012 500 mg will be administered on Day1 of each cycle (once every four weeks), for up to 2 years.
|
|---|---|
|
Infections and infestations
Cellulitis
|
5.6%
1/18 • Number of events 1 • From baseline until disease progression or treatment discontinuation, plus 28 days of follow-up after discontinuation (up to approximately 11.3 months)
The investigator or investigator's team will report all protocol defined SAEs and ECIs to the Sponsor (MedSIR) no later than 24 hours of any site study team staff becoming aware of the event. The full details of the SAE and/or ECI should be collected and fully documented using theSAE form. Follow-up information will be sent along with the SAE form, if available on the day the event is reported or as soon as possible.
|
|
Infections and infestations
Groin infection
|
5.6%
1/18 • Number of events 1 • From baseline until disease progression or treatment discontinuation, plus 28 days of follow-up after discontinuation (up to approximately 11.3 months)
The investigator or investigator's team will report all protocol defined SAEs and ECIs to the Sponsor (MedSIR) no later than 24 hours of any site study team staff becoming aware of the event. The full details of the SAE and/or ECI should be collected and fully documented using theSAE form. Follow-up information will be sent along with the SAE form, if available on the day the event is reported or as soon as possible.
|
|
Infections and infestations
Postoperative wound infection
|
5.6%
1/18 • Number of events 1 • From baseline until disease progression or treatment discontinuation, plus 28 days of follow-up after discontinuation (up to approximately 11.3 months)
The investigator or investigator's team will report all protocol defined SAEs and ECIs to the Sponsor (MedSIR) no later than 24 hours of any site study team staff becoming aware of the event. The full details of the SAE and/or ECI should be collected and fully documented using theSAE form. Follow-up information will be sent along with the SAE form, if available on the day the event is reported or as soon as possible.
|
|
Infections and infestations
Superinfection
|
5.6%
1/18 • Number of events 1 • From baseline until disease progression or treatment discontinuation, plus 28 days of follow-up after discontinuation (up to approximately 11.3 months)
The investigator or investigator's team will report all protocol defined SAEs and ECIs to the Sponsor (MedSIR) no later than 24 hours of any site study team staff becoming aware of the event. The full details of the SAE and/or ECI should be collected and fully documented using theSAE form. Follow-up information will be sent along with the SAE form, if available on the day the event is reported or as soon as possible.
|
|
Infections and infestations
Wound infection
|
5.6%
1/18 • Number of events 1 • From baseline until disease progression or treatment discontinuation, plus 28 days of follow-up after discontinuation (up to approximately 11.3 months)
The investigator or investigator's team will report all protocol defined SAEs and ECIs to the Sponsor (MedSIR) no later than 24 hours of any site study team staff becoming aware of the event. The full details of the SAE and/or ECI should be collected and fully documented using theSAE form. Follow-up information will be sent along with the SAE form, if available on the day the event is reported or as soon as possible.
|
|
Injury, poisoning and procedural complications
Skin wound
|
5.6%
1/18 • Number of events 1 • From baseline until disease progression or treatment discontinuation, plus 28 days of follow-up after discontinuation (up to approximately 11.3 months)
The investigator or investigator's team will report all protocol defined SAEs and ECIs to the Sponsor (MedSIR) no later than 24 hours of any site study team staff becoming aware of the event. The full details of the SAE and/or ECI should be collected and fully documented using theSAE form. Follow-up information will be sent along with the SAE form, if available on the day the event is reported or as soon as possible.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumour ulceration
|
5.6%
1/18 • Number of events 1 • From baseline until disease progression or treatment discontinuation, plus 28 days of follow-up after discontinuation (up to approximately 11.3 months)
The investigator or investigator's team will report all protocol defined SAEs and ECIs to the Sponsor (MedSIR) no later than 24 hours of any site study team staff becoming aware of the event. The full details of the SAE and/or ECI should be collected and fully documented using theSAE form. Follow-up information will be sent along with the SAE form, if available on the day the event is reported or as soon as possible.
|
|
Gastrointestinal disorders
Pancreatitis
|
5.6%
1/18 • Number of events 1 • From baseline until disease progression or treatment discontinuation, plus 28 days of follow-up after discontinuation (up to approximately 11.3 months)
The investigator or investigator's team will report all protocol defined SAEs and ECIs to the Sponsor (MedSIR) no later than 24 hours of any site study team staff becoming aware of the event. The full details of the SAE and/or ECI should be collected and fully documented using theSAE form. Follow-up information will be sent along with the SAE form, if available on the day the event is reported or as soon as possible.
|
|
Investigations
Alanine aminotransferase increased
|
5.6%
1/18 • Number of events 1 • From baseline until disease progression or treatment discontinuation, plus 28 days of follow-up after discontinuation (up to approximately 11.3 months)
The investigator or investigator's team will report all protocol defined SAEs and ECIs to the Sponsor (MedSIR) no later than 24 hours of any site study team staff becoming aware of the event. The full details of the SAE and/or ECI should be collected and fully documented using theSAE form. Follow-up information will be sent along with the SAE form, if available on the day the event is reported or as soon as possible.
|
|
Investigations
Aspartate aminotransferase increased
|
5.6%
1/18 • Number of events 1 • From baseline until disease progression or treatment discontinuation, plus 28 days of follow-up after discontinuation (up to approximately 11.3 months)
The investigator or investigator's team will report all protocol defined SAEs and ECIs to the Sponsor (MedSIR) no later than 24 hours of any site study team staff becoming aware of the event. The full details of the SAE and/or ECI should be collected and fully documented using theSAE form. Follow-up information will be sent along with the SAE form, if available on the day the event is reported or as soon as possible.
|
Other adverse events
| Measure |
Interventional Arm
n=18 participants at risk
Patients will receive INCMGA00012 500 mg by intravenous infusion on Day1 of each cycle.
Retifanlimab: INCMGA00012 500 mg will be administered on Day1 of each cycle (once every four weeks), for up to 2 years.
|
|---|---|
|
Investigations
Transaminases increased
|
5.6%
1/18 • Number of events 2 • From baseline until disease progression or treatment discontinuation, plus 28 days of follow-up after discontinuation (up to approximately 11.3 months)
The investigator or investigator's team will report all protocol defined SAEs and ECIs to the Sponsor (MedSIR) no later than 24 hours of any site study team staff becoming aware of the event. The full details of the SAE and/or ECI should be collected and fully documented using theSAE form. Follow-up information will be sent along with the SAE form, if available on the day the event is reported or as soon as possible.
|
|
General disorders
Fatigue
|
22.2%
4/18 • Number of events 8 • From baseline until disease progression or treatment discontinuation, plus 28 days of follow-up after discontinuation (up to approximately 11.3 months)
The investigator or investigator's team will report all protocol defined SAEs and ECIs to the Sponsor (MedSIR) no later than 24 hours of any site study team staff becoming aware of the event. The full details of the SAE and/or ECI should be collected and fully documented using theSAE form. Follow-up information will be sent along with the SAE form, if available on the day the event is reported or as soon as possible.
|
|
General disorders
Xerosis
|
5.6%
1/18 • Number of events 1 • From baseline until disease progression or treatment discontinuation, plus 28 days of follow-up after discontinuation (up to approximately 11.3 months)
The investigator or investigator's team will report all protocol defined SAEs and ECIs to the Sponsor (MedSIR) no later than 24 hours of any site study team staff becoming aware of the event. The full details of the SAE and/or ECI should be collected and fully documented using theSAE form. Follow-up information will be sent along with the SAE form, if available on the day the event is reported or as soon as possible.
|
|
Skin and subcutaneous tissue disorders
Rash
|
5.6%
1/18 • Number of events 1 • From baseline until disease progression or treatment discontinuation, plus 28 days of follow-up after discontinuation (up to approximately 11.3 months)
The investigator or investigator's team will report all protocol defined SAEs and ECIs to the Sponsor (MedSIR) no later than 24 hours of any site study team staff becoming aware of the event. The full details of the SAE and/or ECI should be collected and fully documented using theSAE form. Follow-up information will be sent along with the SAE form, if available on the day the event is reported or as soon as possible.
|
|
Skin and subcutaneous tissue disorders
Dry skin
|
5.6%
1/18 • Number of events 1 • From baseline until disease progression or treatment discontinuation, plus 28 days of follow-up after discontinuation (up to approximately 11.3 months)
The investigator or investigator's team will report all protocol defined SAEs and ECIs to the Sponsor (MedSIR) no later than 24 hours of any site study team staff becoming aware of the event. The full details of the SAE and/or ECI should be collected and fully documented using theSAE form. Follow-up information will be sent along with the SAE form, if available on the day the event is reported or as soon as possible.
|
|
Skin and subcutaneous tissue disorders
Skin oedema
|
5.6%
1/18 • Number of events 1 • From baseline until disease progression or treatment discontinuation, plus 28 days of follow-up after discontinuation (up to approximately 11.3 months)
The investigator or investigator's team will report all protocol defined SAEs and ECIs to the Sponsor (MedSIR) no later than 24 hours of any site study team staff becoming aware of the event. The full details of the SAE and/or ECI should be collected and fully documented using theSAE form. Follow-up information will be sent along with the SAE form, if available on the day the event is reported or as soon as possible.
|
|
Renal and urinary disorders
Dysuria
|
5.6%
1/18 • Number of events 1 • From baseline until disease progression or treatment discontinuation, plus 28 days of follow-up after discontinuation (up to approximately 11.3 months)
The investigator or investigator's team will report all protocol defined SAEs and ECIs to the Sponsor (MedSIR) no later than 24 hours of any site study team staff becoming aware of the event. The full details of the SAE and/or ECI should be collected and fully documented using theSAE form. Follow-up information will be sent along with the SAE form, if available on the day the event is reported or as soon as possible.
|
|
Musculoskeletal and connective tissue disorders
Arthritis
|
5.6%
1/18 • Number of events 1 • From baseline until disease progression or treatment discontinuation, plus 28 days of follow-up after discontinuation (up to approximately 11.3 months)
The investigator or investigator's team will report all protocol defined SAEs and ECIs to the Sponsor (MedSIR) no later than 24 hours of any site study team staff becoming aware of the event. The full details of the SAE and/or ECI should be collected and fully documented using theSAE form. Follow-up information will be sent along with the SAE form, if available on the day the event is reported or as soon as possible.
|
|
Metabolism and nutrition disorders
Decreased appetite
|
5.6%
1/18 • Number of events 2 • From baseline until disease progression or treatment discontinuation, plus 28 days of follow-up after discontinuation (up to approximately 11.3 months)
The investigator or investigator's team will report all protocol defined SAEs and ECIs to the Sponsor (MedSIR) no later than 24 hours of any site study team staff becoming aware of the event. The full details of the SAE and/or ECI should be collected and fully documented using theSAE form. Follow-up information will be sent along with the SAE form, if available on the day the event is reported or as soon as possible.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place