To assess efficacy of INCMGA00012 in terms of the ORR in participants with locally advanced or metastatic SCAC who have progressed after platinum-based chemotherapy.
ID
Source
Brief title
Condition
- Anal and rectal conditions NEC
- Metastases
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Overall Response Rate, defined as the percentage of participants having a CR
(complete response) or PR (partial response), according to RECIST v1.1 as
determined by ICR (Independent Central Radiographic Review)
Secondary outcome
- DOR (duration of response), defined as the time from an initial objective
response (CR or PR) according to RECIST v1.1 until disease progression as
determined by ICR (Independent Central Radiographic Review) or death due to any
cause.
- DCR (disease control rate), defined as the number of participants maintaining
either an ORR or stable disease.
- PFS (progression free survival), defined as the time from the first dose of
study treatment until disease progression by ICR or death due to any cause.
- OS (Overal survival), defined as the time from the start of therapy until
death due to any cause.
- Safety, determined by the number of participants; the frequency, duration,
and severity of AEs; laboratory tests; vital signs; and ECGs.
- Population PK (Pharmacokinetics), including Cmax, Tmax, Cmin, and AUC0-t,
will be summarized.
Exploratory:
-Blood and/or tumor analytes, immune cell profile, viral profiles, and other
relevant markers will be evaluated with respect to safety and efficacy outcome
measures.
-Immunogenicity, defined as the occurrence of specific ADAs (Anti-drug
Antibodies) to INCMGA00012.
-Efficacy parameters will be evaluated according to iRECIST as assessed by the
investigator.
-Evaluations may include PRO (patient-reported outcome) assessments scheduled
to align with tumor response.
-HIV viral load and CD4+ counts will be monitored in participants who are known
to be HIV-positive.
Background summary
Squamous cell carcinoma of the anal canal (SCAC) accounts for almost 3% of
digestive system cancers and is increasing in frequency due to its association
with HPV and HIV infection. Although most patients have localized disease,
systemic metastases will develop in approximately 25% of patients, and 5-year
survival is poor in these individuals. Chemotherapy with platinum-based
regimens is an accepted standard of care; however, responses are not durable,
and progression-free and overall survival after these treatments is measured
only in months. There are no accepted salvage treatments for patients who
progress after first-line chemotherapy
Immunotherapy, like PD-1 inhibitor MGA00012 may be a promising new approach to
the treatment of metastatic SCAC. This is investigated in this study.
Study objective
To assess efficacy of INCMGA00012 in terms of the ORR in participants with
locally advanced or metastatic SCAC who have progressed after platinum-based
chemotherapy.
Study design
Open-label, single-group, multicenter, Phase 2 study
Intervention
All participants will receive INCMGA00012 at the recommended Phase 2 dose of
500 mg IV Q4W. Treatment will be administered by IV infusion over 60 minutes on
Day 1 of each 28-day cycle.
In order to properly determine the patient's response to the therapy, regularly
blood is taken, CT Scan or MRI is made, urine is collected and asked to
participants to complete quality of live questionnaires on a device.
HIV positive patients are asked if they want to participate in an optional
study. If a patient consents to participate, the amount of blood taken per
study visit differs, this is either 20 ml less or 60 ml more per study visit.
In total about 805 ml blood would be taken from these patients.
Study burden and risks
This therapy might give side effects, like fatigue and vomiting, nausea,
pyrexia (fever), anemia, dehydration. All possible reported AEs seen so far
have been described in the Investigator's Brochure and additional (SUSAR)
reports. In addition the tests to be done might result in some risks, like
drawing blood, taking ECG, MRI, CT scan, biopt.
The study medicine may prove beneficial in this disease or relieve symptoms,
but this is not certain. The information obtained thanks to this study may
contribute to a better knowledge of the use of this medicinal product or to the
development of a new medicinal product for the treatment of Squamous Carcinoma
of the Anal Canal in future patients.
Paasheuvelweg 25
Amsterdam 1105 BP
NL
Paasheuvelweg 25
Amsterdam 1105 BP
NL
Listed location countries
Age
Inclusion criteria
Male and female participants at least 18 years of age with locally advanced or
metastatic SCAC who have progressed after platinum-based chemotherapy.
According to Protocol version 4, dated 08-Jul-2019 an update of the criteria:
a Prior 2 lines of systemic therapy for metastatic disease are permitted.
b Participants who are ineligible for platinum must have received at least 1
prior line of systemic therapy.
c. Participants receiving platinum-based radiosensitizing chemotherapy are
eligible if relapse occurs within 6 months from completion of treatment.
Exclusion criteria
Toxicity of prior therapy that has not recovered to <= Grade 1 or baseline (with
the exception of any grade of alopecia and anemia not requiring transfusion
support).
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2018-002070-51-NL |
| ClinicalTrials.gov | NCT03597295 |
| CCMO | NL67586.068.18 |