Clinical trial NCT04438824: Palbociclib and INCMGA00012 in People With Advanced Liposarcoma
Official title: A Phase II Study of CDK4/6 Inhibition (Palbociclib) Combined With PD-1 Blockade (INCMGA00012) in Patients With Advanced Well-differentiated Dedifferentiated Liposarcoma
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Well-differentiated/Dedifferentiated Liposarcoma
Keywords: Palbociclib
INCMGA00012
20-062
Lead sponsor: Memorial Sloan Kettering Cancer Center
Sponsor class: OTHER
Collaborators: name: Incyte Corporation
First posted: 2020-06-19
Enrollment: 42
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: This is a phase II study of palbociclib plus INCMGA00012 in patients with advanced WD/DD liposarcoma.
Primary purpose: TREATMENT

Brief summary: The researchers are doing this study to find out whether combining the study drugs palbociclib and INCMGA00012 is an effective and safe treatment for advanced liposarcoma.

"Funding Source - FDA OOPD"


Eligibility criteria: Inclusion Criteria:

* A diagnosis of metastatic or unresectable WD/DD liposarcoma. DD liposarcoma must be present. Unresectable is defined as if the primary tumor a) cannot be safely removed surgically or b) would benefit from systemic therapy prior to a surgical approach
* Measurable disease by RECIST 1.1

  a. Target lesions must not be chosen from a previously irradiated field unless there has been radiographically and/or pathologically documented tumor progression in that lesion prior to enrollment
* Age ≥ 18 years
* ECOG performance status 0 or 1
* Adequate organ and marrow function as defined below (ULN indicates institutional upper limit of normal):

  1. Absolute neutrophil count ≥ 1.5 x 109/L
  2. Hemoglobin ≥ 8.0 g/dL
  3. WBC ≥ 3.0 x 109/L
  4. Platelets ≥ 100 x 109/L
  5. ≤ 1.5 X ULN OR Direct bilirubin ≤ ULN for subjects with total bilirubin levels \> 1.5 ULN. Except patients with Gilbert's disease (≤3x ULN)
  6. AST (SGOT) /ALT (SGPT) ≤ 3 x institutional ULN
  7. Creatinine Clearance \> 30 mL/min (calculated by Cockcroft-Gault method)
* Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control or abstinence) during the trial period through at least 120 days after the last dose of study treatment.
* Ability to understand and the willingness to sign a written informed consent document.
* Ability to swallow tablets or capsules
* Patients with brain metastasis that have been treated with definitive surgery or radiation, and have been clinically stable for 3 months are eligible

Exclusion Criteria:

* Patients who have not recovered from clinically significant adverse events of prior therapy to ≤ NCI CTCAE v5 Grade 1, except alopecia and stable neuropathy, which must have resolved to Grade ≤ 2 or baseline.
* Patients receiving any other investigational agents.
* Patients who have received prior treatment with a selective CDK4 inhibitor or an anti-PD-1/PD-L1 agent
* Uncontrolled intercurrent illness including, but not limited to, known ongoing or active infection, including uncontrolled HIV, active hepatitis B or C, symptomatic congestive heart failure, unstable angina pectoris, uncontrolled cardiac arrhythmias, psychiatric illness/social situations that would limit compliance with study requirements, clinically significant interstitial lung disease or active noninfectious pneumonitis, or active infection requiring systemic therapy

  1. Patients with a CD4+ count of \> 300 and an undetectable viral load who are currently on HAART are eligible for inclusion
  2. Patients with NYHA class III or IV congestive heart failure within 6 months of study treatment will be excluded
* Pregnant women and women who are breast-feeding.
* History or evidence of symptomatic autoimmune disease in past 2 years prior to enrollment.

  a. Replacement therapy (e.g., thyroxine for hypothyroidism, insulin for diabetes or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment for autoimmune disease
* Prolonged QTcF \> 450 ms for men and \> 470 ms for women at Screening.
* Patients who have received a live vaccine within 30 days of the start date of the planned study therapy. Note: Seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however intranasal influenza vaccines are live attenuated vaccines, and are not allowed
* Radiation therapy within 2 weeks prior to study Day 1
* Prior organ transplantation including allogenic stem-cell transplantation
* Known prior severe hypersensitivity to investigational product or any component in its formulations, including known severe hypersensitivity reactions to monoclonal antibodies (NCI CTCAE v 5 Grade ≥ 3)
* Patients who require concomitant use of medications that strongly induce or inhibit CYP3A (per section 15.0)

Primary outcomes:
measure: confirm the recommended phase two dose (RP2D
timeFrame: within 6 weeks of treatment
measure: best overall response rate (Phase II)
timeFrame: by 48 weeks
Secondary outcomes:
measure: Safety
timeFrame: 2 years
measure: overall response rate
timeFrame: 48 weeks
Other outcomes:
Locations:
city: Basking Ridge
country: United States
facility: Memorial Sloan Kettering at Basking Ridge (Limited Protocol Activities)
state: New Jersey
city: Middletown
country: United States
facility: Memorial Sloan Kettering Monmouth (Limited Protocol Activities)
state: New Jersey
city: Montvale
country: United States
facility: Memorial Sloan Kettering Bergen (Limited Protocol Activities)
state: New Jersey
city: Commack
country: United States
facility: Memorial Sloan Kettering Suffolk - Commack (Limited Protocol Activities)
state: New York
city: Harrison
country: United States
facility: Memorial Sloan Kettering Westchester (Limited Protocol Activities)
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Rockville Centre
country: United States
facility: Memorial Sloan Kettering Nassau (Limited protocol activities)
state: New York
Study officials:
affiliation: Memorial Sloan Kettering Cancer Center
name: Sandra D'Angelo, MD
role: PRINCIPAL_INVESTIGATOR
References: