A Phase II Study of CDK4/6 Inhibition (Palbociclib) Combined With PD-1 Blockade (INCMGA00012) in Patients With Advanced Well-differentiated Dedifferentiated Liposarcoma
Overview
- Phase
- Phase 2
- Status
- Active, not recruiting
- Enrollment
- 42
- Locations
- 7
- Primary Endpoint
- best overall response rate (Phase II)
Overview
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"
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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):
- •Absolute neutrophil count ≥ 1.5 x 109/L
- •Hemoglobin ≥ 8.0 g/dL
- •WBC ≥ 3.0 x 109/L
- •Platelets ≥ 100 x 109/L
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
- •Patients with a CD4+ count of \> 300 and an undetectable viral load who are currently on HAART are eligible for inclusion
- •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.
Arms & Interventions
Palbociclib and INCMGA00012
Initial design (safety lead-in and expansion): One treatment cycle will consist of 28 days. Patients in both study phases will start palbociclib on Day 1 and INCMGA00012 on day 15 (+/- 7 days) of each cycle at the following dose schedule: INCMGA00012: 500 mg IV (flat dose) q28 days Palbociclib: 125 mg PO daily for 21 days, followed by 7 days off, q28 days Palbociclib will be taken on Day 1 of each cycle for 21 consecutive days followed by 7 days off (days 22-28 of each Cycle). INCMGA00012 will be administered on Day 15 of (+/- 7 days) each cycle and repeat every 28 days.(No longer using this)
Amended design (Expansion only): One treatment cycle will consist of 28 days. Patients in both study phases will start palbociclib and INCMGA00012 on day 1 of each cycle: 500 mg IV (flat dose) of INCMGA00012 will be administered q28 days concurrently with palbociclib 125 mg PO daily for 21 days, followed by 7 days off, q28 days.
Intervention: INCMGA00012 (Drug)
Palbociclib and INCMGA00012
Initial design (safety lead-in and expansion): One treatment cycle will consist of 28 days. Patients in both study phases will start palbociclib on Day 1 and INCMGA00012 on day 15 (+/- 7 days) of each cycle at the following dose schedule: INCMGA00012: 500 mg IV (flat dose) q28 days Palbociclib: 125 mg PO daily for 21 days, followed by 7 days off, q28 days Palbociclib will be taken on Day 1 of each cycle for 21 consecutive days followed by 7 days off (days 22-28 of each Cycle). INCMGA00012 will be administered on Day 15 of (+/- 7 days) each cycle and repeat every 28 days.(No longer using this)
Amended design (Expansion only): One treatment cycle will consist of 28 days. Patients in both study phases will start palbociclib and INCMGA00012 on day 1 of each cycle: 500 mg IV (flat dose) of INCMGA00012 will be administered q28 days concurrently with palbociclib 125 mg PO daily for 21 days, followed by 7 days off, q28 days.
Intervention: Palbociclib (Drug)
Outcomes
Primary Outcomes
best overall response rate (Phase II)
Time Frame: by 48 weeks
defined by RECIST 1.1
confirm the recommended phase two dose (RP2D
Time Frame: within 6 weeks of treatment
DLTs will be assess within the first 6 weeks of the treatment combination . DLT definitions are described in section 15.4, and will be defined using NCI CTCAE v 5.0. If ≤ 1 patient out of 6 has a dose-limiting toxicity, the dosing used in the safety lead-in phase will be declared the recommended phase 2 dose. If ≥ 2 of 6 patients in the safety lead-in experience a DLT, study treatment will be halted and no further patients will be enrolled. If the study is resumed with an alternative dosing schema, a new safety lead-in phase will be completed with the new dosing regimen
Secondary Outcomes
- Safety(2 years)
- overall response rate(48 weeks)