Trial Title:
Phase Ib Study of AlpeliSib With PEmbroLizumab in Patients With mEtastatic Breast caNcer or melanomA (SELENA)
NCT ID:
NCT06545682
Condition:
Myelodysplastic Syndrome(MDS)
Acute Myelogenous Leukemia (AML)
Conditions: Official terms:
Preleukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Myelodysplastic Syndromes
Pembrolizumab
Study type:
Interventional
Study phase:
Phase 1/Phase 2
Overall status:
Not yet recruiting
Study design:
Allocation:
Non-Randomized
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Alpelisib + Pembrolizumab
Description:
Given by mouth (PO) Given by vein (IV)
Arm group label:
Dose Escalation
Arm group label:
Dose Expansion
Other name:
BYL 719
Summary:
To find a recommended dose of the combination of alpelisib and pembrolizumab that can be
given to patients with metastatic breast cancer or melanoma.
Detailed description:
Primary Objective:
To determine the safety and recommended phase 2 dose (RP2D) of nadunolimab in combination
with azacitidine in intermediate/high/very high risk MDS (International prognostic
scoring system revised/IPSS-R) who are untreated or had up to 2 prior treatments or in
combination with azacitidine and venetoclax in patients with relapsed/refractory AML
receiving treatment as first or second salvage.
Secondary Objectives:
- To assess the complete remission (CR)+ CR with incomplete count recovery (CRi) +
partial remission (PR)+ morphologic leukemia free state (MLFS) rate as per European
Leukemia Network 2017 AML response criteria within 6 cycles of treatment initiation
in patients with relapsed refractory AML
- To assess Overall Response Rate (ORR) defined as [CR + marrow complete remission
(mCR) + partial remission (PR) + CR with partial hematologic recovery (CRh) +
hematological improvement (HI)] as per International Working Group 2023 criteria for
MDS in patients with intermediate, high, very high risk MDS (IPSS-R) within 6 cycles
of treatment initiation.
- To determine the duration of response (DOR)
Exploratory Objectives:
To assess effects on exploratory biomarkers, including serum biomarkers, alterations in
hematopoietic subpopulations as measured by multicolor flow cytometry and multimodal
single cell analysis, and effects on the leukemic cells as assessed by gene panel
analysis and/or single cell DNA-analysis.
To evaluate exposure by measuring PK.
To evaluate immunogenicity by assessing antidrug antibodies (ADA).
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Patients must be 18 years or older.
2. Patients must be willing and able to provide informed consent.
3. In the dose escalation, patients must have histologically documented locally
advanced, unresectable, or metastatic melanoma or TNBC that has progressed on
treatments that are known to prolong survival or for which no standard treatment is
available or refused such therapy. Presence of active brain metastases is not
required. Patients with active metastases as defined below can be eligible in the
dose escalation.
4. In the dose expansion, patients must have histologically documented locally
advanced, unresectable, or metastatic melanoma or TNBC that has progressed on
treatments that are known to prolong survival or for which no standard treatment is
available or refused such therapy.
1. Melanoma patients without brain metastases who have progressed on an anti-PD-1
or anti-PD-L1-based regimen.
2. Melanoma patients with active and untreated brain metastases who have
progressed on an anti-PD-1 or anti-PD-L1-based regimen.
3. TNBC patients (defined as ER <1%, HER2 0, 1+, 2+, and fluorescence in situ
hybridization negative) with active untreated brain metastases. Prior treatment
with anti-PD-1/anti-PD-L1 is not required.
5. All patients must have had a brain magnetic resonance imaging (MRI) scan in the
previous 28 days to confirm eligibility for the following cohorts:
1. Dose escalation and dose expansion Cohort 1: Confirmed absence of untreated
brain metastases in patients with histologically confirmed advanced melanoma.
Prior surgery for brain metastases must have been completed at least 4 weeks
prior study treatment initiation, whole brain radiation therapy must have been
completed at least 3 weeks prior to study treatment initiation, and
stereotactic radiosurgery must have been completed within 7 days prior to study
treatment initiation.
2. Dose escalation and dose expansion Cohorts 2 and 3: At least one confirmed
measurable untreated brain lesion ≥ 0.5 cm and < 3.0 cm in the longest axis.
6. Has measurable disease based on the RECIST v1.1.
7. Has adequate organ function as defined in Table 2:
8. Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
(Appendix 4).
9. Has a life expectancy of at least 12 weeks.
10. Able to swallow and retain orally administered medication.
11. In the dose expansion, patients with EC disease must be willing to provide tissue
from a newly obtained, safely accessible core or excisional biopsy lesion at
pre-treatment and at least one time point while on study treatment. Correlative
biopsies will be optional in the dose escalation portion of the study. Newly
obtained biopsy is defined as a specimen obtained up to 6 weeks (42 days) prior to
initiation of study treatment on Day 1 without intervening systemic therapy.
12. Women of childbearing potential (WOCBP) should have a negative urine pregnancy test
within 72 hours prior to receiving the first dose of study treatment. If the urine
test is positive or cannot be confirmed as negative, a serum pregnancy test will be
required.
13. Alpelisib and pembrolizumab can cause fetal harm when administered to a pregnant
woman. Therefore, WOCBP must agree to use adequate contraception (hormonal or
barrier method of birth control; abstinence) from the time of screening through 4
months after the last dose of study treatment. Refer to Pregnancy Assessment Policy
MD Anderson Cancer Center (MDACC) Institutional Policy # CLN1114. This includes all
female patients between the onset of menses and 55 years unless the patient presents
with an applicable exclusionary factor such as one of the following:
1. Postmenopausal (no menses in ≥ 12 consecutive months)
2. History of hysterectomy or bilateral salpingo-oophorectomy
3. Ovarian failure (follicle-stimulating hormone and estradiol in menopausal range
and have received whole pelvic radiation therapy)
4. History of bilateral tubal ligation or another surgical sterilization procedure
14. Approved methods of birth control are as follows: hormonal contraception (i.e.,
birth control pills, injection, implant, transdermal patch, vaginal ring),
intrauterine device, tubal ligation or hysterectomy, patient/partner post vasectomy,
implantable or injectable contraceptives, and condoms plus spermicide. Not engaging
in sexual activity for the total duration of the study and the study treatment
washout period is an acceptable practice; however, periodic abstinence, the rhythm
method, and the withdrawal method are not acceptable methods of birth control.
Should a woman become pregnant or suspect she is pregnant while she or her partner
is participating in this study, she should inform her treating physician
immediately.
15. Male patients with partner(s) of childbearing potential must agree to use adequate
contraception from the time of screening through 4 months after the last dose of
study treatment.
Exclusion Criteria:
1. Has a history of or active autoimmune disease, as follows: history of inflammatory
bowel disease, history of symptomatic disease (e.g., rheumatoid arthritis, systemic
progressive sclerosis [scleroderma], systemic lupus erythematosus, autoimmune
vasculitis [e.g., Wegener's granulomatosis]), motor neuropathy considered of
autoimmune origin (e.g., Guillain-Barré syndrome and myasthenia gravis), or history
of autoimmune thyroiditis (patients may be eligible if their current thyroid
disorder is treated and stable with replacement or other medical therapy).
2. Has active infection or had a serious general medical condition(s) (such as vascular
accident) in the past 6 months.
3. Any unresolved > Grade 1 toxicity (per CTCAE v5.0) from previous anticancer therapy
or previously administered agent at the time of enrollment, except for alopecia and
Grade 2 anemia (if hemoglobin is > 9 g/dL). Note: If the patient received major
surgery, he/she must have recovered adequately from the toxicity and/or
complications from the intervention prior to starting study treatment.
4. Patients who received chemotherapy or radiotherapy within 2 weeks (6 weeks for
nitrosoureas or mitomycin C) prior to starting study treatment.
5. Presence of any clinically significant gastrointestinal abnormality or other
condition(s) (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea,
malabsorption syndrome, or small bowel resection) that may alter absorption such as
malabsorption syndrome or major resection of the stomach or substantial portion of
the small intestine based on investigator discretion.
6. Previous major surgery within 14 days prior to enrollment.
7. Evidence of severe or uncontrolled systemic disease (e.g., unstable or uncompensated
respiratory, hepatic, renal, or cardiac disease).
8. Established diagnosis of diabetes mellitus type I or uncontrolled type II (based on
fasting blood glucose and HbA1c [see inclusion criteria #4]).
9. History of acute pancreatitis within 1 year of screening or past medical history of
chronic pancreatitis.
10. History of severe cutaneous reaction, such as SJS, erythema multiforme (EM), TEN, or
drug reaction with eosinophilia and systemic symptoms (DRESS).
11. Based on average of triplicate 12-lead electrocardiogram (ECG), a mean resting QTc
interval using Fridericia formula > 450 msec for males and > 470 msec for females at
screening or a history of congenital long QT syndrome or QTc > 480 msec for patients
with a bundle branch block.
12. History or evidence of cardiovascular risk including any of the following:
1. History of myocardial infarction, acute coronary syndromes (including unstable
angina), coronary angioplasty, stenting, or bypass grafting within 6 months
prior to enrollment.
2. Class III or IV heart failure as defined by the New York Heart Association
functional classification system.
3. Known left ventricular ejection fraction < 50%.
4. Known cardiac metastases.
13. Poorly controlled hypertension (defined as systolic blood pressure ≥150 mmHg or
diastolic blood pressure >100 mmHg based on a mean of three measurements taken at
approximately 2-minute intervals).
Note: Initiation or adjustment of antihypertensive medication(s) is permitted if
done 30 or more days prior to enrollment.
14. For dose expansion Cohorts 2 and 3 with active brain metastases:
1. Patients must not have any of the following on the screening brain MRI:
- Any untreated brain lesions > 3.0 cm in size.
- Any brain lesion thought to require immediate local therapy, including
(but not limited to) a lesion in an anatomic site where increase in size
or possible treatment-related edema may pose risk to the patient (e.g.,
brainstem lesions). Patients who undergo local treatment for such lesions
may still be eligible for the study.
2. Ongoing use of systemic corticosteroids for control of symptoms of brain
metastases at a total daily dose of dexamethasone (or equivalent) > 4 mg.
- Poorly controlled (> 1/week) generalized or complex partial seizures, or
manifestation of neurologic progression due to brain metastases
notwithstanding CNS-directed therapy.
15. Has a history of (non-infectious) pneumonitis that required steroids or current
pneumonitis.
16. Has a history or current evidence of any condition, therapy, or laboratory
abnormality that might confound the results of the trial, interfere with the
patient's participation for the full duration of the trial, or is not in the best
interest of the patient to participate, in the opinion of the treating investigator.
17. Has known psychiatric or substance abuse disorder that in the opinion of the
treating physician or principal investigator (PI) would interfere with cooperation
with the requirements of the trial.
18. Known history of hepatitis B or C or positive test for human immunodeficiency virus.
19. Has received a live vaccine within 30 days of planned start of study treatment.
Note: Seasonal influenza vaccines for injection are generally inactivated flu
vaccines and are allowed; COVID-19 vaccines are allowed; however intranasal
influenza vaccines (e.g., Flu-Mist®) are live attenuated vaccines, and are not
allowed.
20. Current use of or anticipated requirement during the study of any prohibited
medication(s) (See Section 5.5.2).
21. History of allergic reactions attributed to compounds of similar chemical or
biologic composition to alpelisib and pembrolizumab.
22. Pregnant or nursing.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
MD Anderson Cancer Center
Address:
City:
Houston
Zip:
77030
Country:
United States
Contact:
Last name:
Ecaterina Dumbrava, MD
Phone:
713-792-3934
Email:
eeileana@mdanderson.org
Start date:
December 1, 2024
Completion date:
August 3, 2029
Lead sponsor:
Agency:
M.D. Anderson Cancer Center
Agency class:
Other
Source:
M.D. Anderson Cancer Center
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06545682
http://www.mdanderson.org
