Trial Title:
Avelumab and M1774 in ARID1A-mutated Endometrial Cancer (Prior IO)
NCT ID:
NCT06518564
Condition:
Endometrial Cancer
ARID1A Gene Mutation
Recurrent Endometrial Carcinoma
Conditions: Official terms:
Endometrial Neoplasms
Recurrence
Avelumab
Imidazole
Conditions: Keywords:
Endometrial Cancer
ARID1A Mutated Recurrent Endometrial Cancer
Recurrent Endometrial Cancer
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Not yet recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Avelumab
Description:
Human IgG1 antibody, 20mL single-use vials, via intravenous (into the vein) infusion per
protocol.
Arm group label:
Avelumab and M1774
Other name:
MSB0010718C
Intervention type:
Drug
Intervention name:
M1774
Description:
Ataxia Telangiectasia and Rad3-related protein (ATR) inhibitor, 30 and 50 mg capsules,
taken orally per protocol.
Arm group label:
Avelumab and M1774
Other name:
MSC2584415A
Other name:
Tuvusertib
Other name:
VXc-400
Other name:
VRT-1363004
Other name:
2-Amino-6-fluoro-pyrazolo[1,5-a] pyrimidine-3-carboxylic acid [5-fluoro-4-(3-methyl-3H-imidazol-4-yl)-pyridin-3-yl]-amide
Summary:
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)
Detailed description:
This is a non-randomized, open-label, two-stage, phase 2 trial of avelumab in combination
with ATR inhibitor (ATRi) M1774 in participants with ARID1A-mutated endometrial cancers
who have received prior immunotherapy.
The U.S. Food and Drug Administration (FDA) has not approved avelumab for ARID1A-mutated
recurrent endometrial cancer but it has been approved for other uses. The FDA has not
approved M1774 as a treatment for any disease.
The research study procedures including screening for eligibility, in-clinic treatment
visits, blood tests, urine tests, Computerized Tomography (CT) scans or Magnetic
Resonance Imaging (MRI) scans, and electrocardiograms (ECGs).
Participants will receive study treatment for up to 2 years and will be followed for up
to 3 years until the study is complete.
It is expected that about 25 people will take part in this research study.
EMD Serono is supporting this research study by providing the study drugs avelumab and
M1774.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- 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.
--Prior hormonal therapy is allowed (no washout period is required after hormonal
therapy).
- Participants must have received prior immunotherapy targeting the PD-1/PD-L1 pathway
either in the adjuvant, first-line or recurrent setting.
- Age ≥18 years. Because no dosing or adverse event data are currently available on
the use of the combination of avelumab and M1774 in participants <18 years of age,
children are excluded from this study.
- ECOG performance status 0, 1, or 2 (reference Appendix A for ECOG performance status
criteria).
- Availability of a formalin fixed paraffin embedded (FFPE) block of cancer tissue OR
15 unstained 5-micron slides from the original surgery or biopsy or from a biopsy of
recurrent disease.
- Participants must meet the following organ and marrow function as defined below:
- Absolute neutrophil count ≥ 1,500/mcL
- Hemoglobin ≥ 9.0 g/dL (with no erythropoietin or red blood cell transfusion
within the last 14 days)
- Platelets ≥ 100,000/mcL
- Total bilirubin ≤ 1.5 institutional upper limit of normal (ULN) in the case of
documented Gilbert's syndrome, total bilirubin ≤3 x ULN is allowed
- AST(SGOT)/ALT(SGPT) ≤ 2.5 × institutional ULN
- Creatinine clearance ≥ 60 mL/min as estimated by the Cockcroft-Gault formula or
institutional standard method OR
- Glomerular filtration rate (GFR) ≥ 60 mL/min by measured 24-hour urine
collection
- The effects of avelumab and M1774 on the developing human fetus are unknown. For
this reason and because these agents are known to be teratogenic, women of
child-bearing potential must have a negative serum pregnancy test at screening.
Women of child- bearing potential must agree to use adequate contraception (hormonal
or barrier method of birth control; abstinence) prior to study entry, for the
duration of study participation, and for at least 30 days after last avelumab
treatment administration and at least 6 months after last M1774 treatment
administration. Should a woman become pregnant or suspect she is pregnant while she
is participating in this study, she should inform her treating physician
immediately.
--Women of child-bearing potential are defined as those who are not surgically
sterile (i.e., bilateral tubal ligation or salpingectomy, bilateral oophorectomy, or
total hysterectomy) or post-menopausal (defined as ≥ 12 months with no menses
without an alternative medical cause)
- Ability to understand and the willingness to sign a written informed consent
document.
Exclusion Criteria:
- Participants who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for
nitrosoureas or mitomycin C) prior to entering the study.
- 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.
- Known prior severe hypersensitivity to avelumab or M1774 or any component in its
formulations, including known severe hypersensitivity reactions to monoclonal
antibodies (≥ Grade 3), any history of anaphylaxis, or uncontrolled asthma (that is,
3 or more features of partially controlled asthma)
- Active and/or uncontrolled infection. The following exceptions apply:
- Participants with HIV infection are eligible if they are on effective
antiretroviral therapy with undetectable viral load within 6 months, provided
there is no expected drug-drug interaction
- Participants with evidence of chronic HBV infection are eligible if the HBV
viral load is undetectable on suppressive therapy (if indicated), and if they
have ALT, AST, and total bilirubin levels < ULN, and provided there is no
expected drug- drug interaction
- Participants with a history of HCV infection are eligible if they have been treated
and cured. For participants with HCV infection who are currently on treatment, they
are eligible if they have an undetectable HCV viral load, and if they have ALT, AST,
and total bilirubin levels < ULN.
- Participants requiring hormone replacement with corticosteroids are eligible if the
steroids are administered only for the purpose of hormonal replacement and at doses
≤ 10 mg or 10 mg equivalent prednisone per day.
- Current or prior use of immunosuppressive medication within 7 days prior to
enrollment with the following exceptions to this exclusion criterion:
- Intranasal, inhaled, topical steroids, or local steroid injections (e.g.,
intra-articular injection);
- Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of
prednisone or equivalent;
- Steroids as premedication for hypersensitivity reactions (e.g., CT scan
premedication).
- Active autoimmune disease that might deteriorate when receiving an immunostimulatory
agent. Patients with diabetes type I, vitiligo, psoriasis, hypo- or hyperthyroid
disease not requiring immunosuppressive treatment are eligible.
- History of prior organ transplantation including allogeneic stem-cell
transplantation.
- Severe gastrointestinal conditions such as clinical or radiological evidence of
bowel obstruction within 4 weeks prior to study entry, uncontrolled diarrhea in the
last 4 weeks prior to enrollment, or history of inflammatory bowel disease.
- Participants with psychiatric conditions (including active or recent [within the
past year] suicidal ideation of behavior)/social situations that, in the judgment of
the investigator, would make the participant inappropriate for study entry.
- Participants with uncontrolled or poorly controlled arterial hypertension,
symptomatic congestive heart failure (≥ New York Heart Association Classification
Class III), uncontrolled cardiac arrhythmia, unstable angina pectoris, myocardial
infarction or a coronary revascularization procedure, cerebral vascular incident,
transient ischemic attack, or any other significant vascular disease within 180 days
of study intervention start.
- Known alcohol or drug abuse.
- Individuals with a history of a different malignancy are ineligible except for the
following circumstances: Individuals with a history of other malignancies are
eligible if they have been disease-free for at least 5 years or if they are deemed
by the investigator to be at low risk for recurrence of that malignancy. Individuals
with the following cancers are eligible if diagnosed and treated within the past 5
years: breast cancer in situ, cervical cancer in situ, and basal cell or squamous
cell carcinoma of the skin.
- All other severe acute or chronic medical conditions (for example, immune colitis,
inflammatory bowel disease, uncontrolled asthma, immune pneumonitis, or pulmonary
fibrosis) or laboratory abnormalities that may increase the risk associated with
study participation or study treatment administration in the opinion of the
investigator and would make the participant inappropriate for entry into the study.
- Vaccination within 4 weeks of treatment initiation and while on trial is prohibited
except for administration of inactivated vaccines.
- Patients may not use natural herbal products or other "folk remedies" while
participating in this study. Herbal medications include, but are not limited to St.
John's Wort, Kava, ephedra (ma huang), gingko biloba, dehydroepiandrosterone (DHEA),
yohimbe, saw palmetto, and ginseng.
- Participants receiving any medications or substances that are strong inhibitors or
inducers of CYP3A4 or CYP1A2 enzymes, proton pump inhibitors, or other prohibited
concomitant medications within 7 days prior to treatment initiation are ineligible.
Examples are provided in Appendix B. Because the lists of these agents are
constantly changing, it is important to regularly consult a frequently-updated
medical reference. As part of the enrollment/informed consent procedures, the
participant will be counseled on the risk of interactions with other agents, and
what to do if new medications need to be prescribed or if the participant is
considering a new over-the-counter medicine or herbal product.
- Pregnant women are excluded from this study because avelumab and M1774 are agents
with the potential for teratogenic or abortifacient effects. Because there is an
unknown but potential risk for adverse events in nursing infants secondary to
treatment of the mother with these agents, breastfeeding should be discontinued if
the mother is treated with either agent. Women should not breastfeed during the
study and for at least 1 month after last treatment administration.
- Calculated QTc average (using the Fridericia correction calculation) of > 470 msec
that does not resolve with correction of electrolyte abnormalities.
Gender:
Female
Gender based:
Yes
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Dana-Farber Cancer Institute
Address:
City:
Boston
Zip:
02115
Country:
United States
Contact:
Last name:
Panagiotis A Konstantinopoulos, MD, PhD
Phone:
617-632-5269
Email:
Panagiotis_Konstantinopoulos@dfci.harvard.edu
Contact backup:
Last name:
Panagiotis A Konstantinopoulos, MD, PhD
Facility:
Name:
Brigham and Women's Hospital
Address:
City:
Boston
Zip:
02215
Country:
United States
Contact:
Last name:
Panagiotis Konstantinopoulos, MD, PhD
Phone:
617-632-5269
Email:
Panagiotis_Konstantinopoulos@dfci.harvard.edu
Contact backup:
Last name:
Panagiotis Konstantinopoulos, MD, PhD
Start date:
January 2025
Completion date:
August 31, 2029
Lead sponsor:
Agency:
Panagiotis Konstantinopoulos, MD, PhD
Agency class:
Other
Collaborator:
Agency:
EMD Serono
Agency class:
Industry
Collaborator:
Agency:
The Applebaum Foundation
Agency class:
Other
Source:
Dana-Farber Cancer Institute
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06518564
