Avelumab and M1774 in ARID1A-mutated Endometrial Cancer
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexFemale
Age18+
SponsorPanagiotis Konstantinopoulos, MD, PhD
About this trial
The purpose of this research study is to see if the combination of study drugs avelumab and M1774 is effective and safe for participants with endometrial cancer.
The names of the study drugs involved in this study are:
* Avelumab (a type of human IgG1 antibody) * M1774 (a type of ATR inhibitor)
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Participants must have endometrial cancer that is ARID1A-mutated [loss of function (LOF) mutations] determined by any CLIA-certified next-generation sequencing assay. ARID1A LOF mutation status must be confirmed by the principal investigator prior to participant enrollment.
Participants must have measurable disease per RECIST 1.1, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions). Each lesion must be >= 10 mm when measured by CT, MRI or caliper measurement by clinical exam; or >= 20 mm when measured by chest x-ray. Lymph nodes must be > 15 mm in short axis when measured by CT or MRI.
Prior Therapy: There is no upper limit of prior therapies, but patients must have had one prior chemotherapeutic regimen for management of endometrial carcinoma. Initial treatment may include chemotherapy, chemotherapy and radiation therapy, and/or consolidation/maintenance therapy. Furthermore, patients who have only received chemotherapy with immunotherapy in the adjuvant setting will be eligible for the study.
Participants must have received prior immunotherapy targeting the PD-1/PD-L1 pathway either in the adjuvant, first-line or recurrent setting. Up to 50% of participants (i.e. a maximum of 12 participants) who do not meet this requirement may enroll in the study.
Disqualifiers
Participants who have had chemotherapy, immunotherapy, other investigational therapy, or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study. There is no required washout period for hormonal therapy.
Participants whose adverse events due to prior anti-cancer therapy have not recovered to ≤ Grade 1, unless toxicity does not constitute a safety risk and/or is stable on supportive therapy in the opinion of the investigator (e.g., alopecia, sensory neuropathy ≤ Grade 2, etc.)
Participants who are receiving any other investigational agents.
Participants with clinically controlled brain metastases, which is defined as individuals with central nervous system metastases that have been treated for, are asymptomatic, and have discontinued corticosteroids for > 14 days or are on a stable or decreasing steroid dose (for the treatment of brain metastases) may be enrolled. Participants with meningeal carcinomatosis are excluded.
Trial design
Design model
Single group
Treatments tested in this trial
Avelumab
DrugHuman IgG1 antibody, 20mL single-use vials, via intravenous (into the vein) infusion per protocol.
M1774
DrugAtaxia Telangiectasia and Rad3-related protein (ATR) inhibitor, 30 and 50 mg capsules, taken orally per protocol.
Treatment groups
25 Participants
are divided into 1 treatment groupGroup A: Avelumab and M1774Experimental treatment 2 interventions
Trial outcomes
Primary outcomes
1
Progression Free Survival at 6 months (PFS6)
PFS6 is the percent probability estimate at 6 months based on the Kaplan-Meier method. PFS is defined as the duration of time from study entry to documented disease progression (PD) or death. Participants alive without PD were censored at the earliest of the date of the last disease evaluation or start of new anticancer therapy. Per RECIST 1.1 for target lesions: PD is at least a 20% increase in the sum of longest diameter (LD) of target lesions, taking as reference the smallest sum on study with at least 5 mm absolute increase. For non-target lesions, progression-free means no new lesions or unequivocal progression on existing non-target lesions or not evaluated.
Time frame
The observation period related to this endpoint is up to 6 months.2
Objective Response Rate (ORR)
ORR was defined as the percentage of participants achieving complete response (CR) or partial response (PR) on treatment based on RECIST 1.1 criteria. Per RECIST 1.1 for target lesions: CR is complete disappearance of all target lesions and PR is at least a 30% decrease in the sum of longest diameter (LD) of target lesions, taking as reference baseline sum LD. PR or better overall response assumes at a minimum incomplete response/stable disease (SD) for the evaluation of non-target lesions and absence of new lesions.
Time frame
The observation period related to this endpoint is up to 2 years.Secondary outcomes
1
Median Progression Free Survival (PFS)
PFS based on Kaplan-Meier methodology was defined as the duration of time from study entry to documented disease progression (PD) requiring removal from the study or death. Participants alive without PD were censored at the earliest of the date of the last disease evaluation or start of new anticancer therapy. Per RECIST 1.1 for target lesions: PD is at least a 20% increase in sum LD, taking as reference the smallest sum on study with at least 5 mm absolute increase. For non-target lesions, progression-free means no new lesions or unequivocal progression on existing non-target lesions or not evaluated.
Time frame
The observation period related to this endpoint is up to 2 years.2
Median Overall Survival (OS)
Overall survival based on the Kaplan-Meier method is defined as the time from registration to death. Participants alive are censored at the last date of contact (including lost-to-follow-up) or at the date of withdrawal of consent, if relevant.
Time frame
The observation period related to this endpoint is up to 5 years.3
Immune-Related Overall Response Rate(irORR)
irORR was defined as the percentage of participants achieving immune-related complete response (irCR) or immune-related partial response (irPR) on treatment based on irRECIST criteria.
Time frame
The observation period related to this endpoint is up to 2 years.4
Median Immune-related Progression-free Survival (irPFS)
Immune-related progression-free survival (irPFS) rate is defined as time from treatment assignment to death or to immune-related progression of disease (irPD). Per ir RECIST, irPD was defined as Sum of the diameters (longest for non-nodal lesions, shortest for nodal lesions) of target and new measurable lesions increases \>= 20% (compared to nadir), confirmed by a repeat, consecutive observation at least 4 weeks from the date first documented, at the investigator's discretion.
Time frame
The observation period related to this endpoint is up to 2 years.Sponsors and contacts
Click on the lead sponsor to view all of their trials.
Panagiotis Konstantinopoulos, MD, PhD
Lead sponsor
Dana-Farber Cancer Institute
Sponsor institution
EMD Serono
Collaborator
The Applebaum Foundation
Collaborator
Source ClinicalTrials.gov