Phase Ib Study of AlpeliSib With PEmbroLizumab in Patients With mEtastatic Breast caNcer or melanomA (SELENA)

NCT06545682 | Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: 2024-0173NCI-2024-06339
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Melanoma (Skin Cancer); Breast Cancer; Brain Metastasases

Outcome Measures

Primary Outcomes (1)

• Adverse Events

  Incidence of Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 5.0

  Through study completion; an average of 1 year.

Study Arms (2)

Dose Escalation

EXPERIMENTAL

Study treatment will be administered on an outpatient basis.

Drug: Alpelisib + Pembrolizumab

Dose Expansion

EXPERIMENTAL

Study treatment will be administered on an outpatient basis.

Drug: Alpelisib + Pembrolizumab

Interventions

Alpelisib + Pembrolizumab DRUG

Given by mouth (PO) Given by vein (IV)

Also known as: BYL 719

Dose Escalation; Dose Expansion

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must be 18 years or older.
• Patients must be willing and able to provide informed consent.
• 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.
• 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.
• Melanoma patients without brain metastases who have progressed on an anti-PD-1 or anti-PD-L1-based regimen.
• Melanoma patients with active and untreated brain metastases who have progressed on an anti-PD-1 or anti-PD-L1-based regimen.
• 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.
• All patients must have had a brain magnetic resonance imaging (MRI) scan in the previous 28 days to confirm eligibility for the following cohorts:
• 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.
• 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.
• Has measurable disease based on the RECIST v1.1.
• Has adequate organ function as defined in Table 2:
• Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 (Appendix 4).
• Has a life expectancy of at least 12 weeks.
• Able to swallow and retain orally administered medication.

You may not qualify if:

• 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).
• Has active infection or had a serious general medical condition(s) (such as vascular accident) in the past 6 months.
• 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.
• Patients who received chemotherapy or radiotherapy within 2 weeks (6 weeks for nitrosoureas or mitomycin C) prior to starting study treatment.
• 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.
• Previous major surgery within 14 days prior to enrollment.
• Evidence of severe or uncontrolled systemic disease (e.g., unstable or uncompensated respiratory, hepatic, renal, or cardiac disease).
• History of acute pancreatitis within 1 year of screening or past medical history of chronic pancreatitis.
• History of severe cutaneous reaction, such as SJS, erythema multiforme (EM), TEN, or drug reaction with eosinophilia and systemic symptoms (DRESS).
• 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.
• History or evidence of cardiovascular risk including any of the following:
• History of myocardial infarction, acute coronary syndromes (including unstable angina), coronary angioplasty, stenting, or bypass grafting within 6 months prior to enrollment.
• Class III or IV heart failure as defined by the New York Heart Association functional classification system.
• Known left ventricular ejection fraction \< 50%.
• Known cardiac metastases.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead

Study Sites (1)

MD Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

Related Links

• MD Anderson Cancer Center Website

MeSH Terms

Conditions

Melanoma; Breast Neoplasms

Interventions

Alpelisib; pembrolizumab

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases; Breast Diseases

Study Officials

• Ecaterina Dumbrava, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Ecaterina Dumbrava, MD

CONTACT

(713) 792-3934; eeileana@mdanderson.org

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 6, 2024
• First Posted: August 9, 2024
• Study Start: October 15, 2024
• Primary Completion (Estimated): August 3, 2027
• Study Completion (Estimated): August 3, 2029
• Last Updated: April 16, 2026

Record last verified: 2026-04

Locations

US (1)