Palbociclib + INCMGA00012 for Liposarcoma

Not currently recruiting at 6 trial locations

Overseen By William Tap, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Memorial Sloan Kettering Cancer Center

Must not be taking: CDK4 inhibitors, Anti-PD-1/PD-L1

Disqualifiers: Uncontrolled illness, Autoimmune disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 48 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether combining two drugs, palbociclib and INCMGA00012 (also known as Retifanlimab, an immunotherapy), can effectively and safely treat advanced liposarcoma, a cancer affecting fat cells. Researchers aim to determine if this drug pairing can manage the disease when surgery isn't an option. This trial may suit those with advanced liposarcoma that cannot be surgically removed and who have remained stable after recent brain metastasis treatments. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot take medications that strongly affect CYP3A enzymes. It's best to discuss your current medications with the trial team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that palbociclib has been tested in patients with advanced liposarcoma and demonstrated some ability to fight tumors, suggesting it might help treat this type of cancer. However, specific safety information for using palbociclib with INCMGA00012 (retifanlimab) remains limited.

Palbociclib is generally used in other cancer treatments, indicating it is somewhat well-tolerated. However, combining drugs can sometimes cause different side effects than when each is used alone. As this trial is in an early stage, researchers are still learning about the safety of this combination for patients with liposarcoma. Participants in the trial will be closely monitored for any side effects. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of Palbociclib and INCMGA00012 for treating liposarcoma because it introduces a novel approach compared to existing options like chemotherapy and surgery. Palbociclib is known for its ability to inhibit cancer cell growth by targeting specific proteins that regulate the cell cycle, while INCMGA00012 is an immunotherapy that enhances the body's immune response against cancer cells. This dual-action approach, combining cell cycle inhibition with immune system activation, offers a promising new mechanism that could potentially improve treatment outcomes for patients with liposarcoma.

What evidence suggests that the combination of palbociclib and INCMGA00012 could be an effective treatment for liposarcoma?

Research has shown that using palbociclib and INCMGA00012 together, as studied in this trial, may help treat advanced liposarcoma. In previous studies, about 14% of patients experienced significant tumor shrinkage. Another 21% showed signs of improvement, although not confirmed. The disease control rate, which measures how well the disease is managed during treatment, was 50%. This indicates that half of the patients had either stable disease or tumor shrinkage. These results suggest that this combination might effectively slow the growth of liposarcoma. ^{1 2 3 4 6}

Who Is on the Research Team?

Sandra D'Angelo, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults with advanced liposarcoma that can't be removed by surgery or needs systemic therapy before an operation. Participants must have measurable disease, agree to use contraception, and have stable brain metastasis if present. They should not have had prior CDK4 inhibitor or anti-PD-1/PD-L1 treatment, uncontrolled illnesses, symptomatic heart failure, severe autoimmune disease in the past 2 years, certain infections like HIV or hepatitis B/C unless controlled.

Inclusion Criteria

I can swallow pills.

AST (SGOT) /ALT (SGPT) ≤ 3 x institutional ULN

Creatinine Clearance > 50 mL/min (calculated by Cockcroft-Gault method)

Exclusion Criteria

I am on replacement therapy for a condition like hypothyroidism, diabetes, or adrenal insufficiency.

I have not had severe heart failure in the last 6 months.

You are currently taking any other experimental drugs or treatments.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive palbociclib and INCMGA00012 in 28-day cycles. Palbociclib is taken daily for 21 days followed by 7 days off, and INCMGA00012 is administered every 28 days.

48 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Long-term Safety Follow-up

Safety will be assessed using CTCAE v 5.0 to define the adverse event profile of the treatment combination.

2 years

What Are the Treatments Tested in This Trial?

Interventions

• INCMGA00012
• Palbociclib

Trial Overview The study is testing the combination of palbociclib and INCMGA00012 as a treatment for advanced liposarcoma. It aims to determine whether this drug duo is effective and safe for patients who meet specific health criteria.

How Is the Trial Designed?

Group I: Palbociclib and INCMGA00012 Experimental Treatment 2 Interventions

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.

INCMGA00012 is already approved in United States, European Union for the following indications:

Approved in United States as Zynyz for:

• Metastatic or recurrent locally advanced Merkel cell carcinoma

Approved in European Union as Zynyz for:

• Metastatic or recurrent locally advanced Merkel cell carcinoma

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

Incyte Corporation

Industry Sponsor

Trials

408

Recruited

66,800+

Steven Stein

Incyte Corporation

Chief Medical Officer since 2015

MD from University of Witwatersrand

Hervé Hoppenot

Incyte Corporation

Chief Executive Officer since 2014

MBA from ESSEC Business School

Published Research Related to This Trial

In a study of 61 patients with well-differentiated and dedifferentiated liposarcoma treated with palbociclib, the median progression-free survival was only 9.2 months for WDLPS and 2.6 months for DDLPS, indicating limited efficacy of the treatment.

Surgical outcomes showed that while some patients underwent successful resections after palbociclib treatment, there was no overall survival benefit, and the treatment did not significantly prolong tumor control.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-world use of palbociclib monotherapy in retroperitoneal liposarcomas at a large volume sarcoma center. Nassif, EF., Cope, B., Traweek, R., et al.[2023]

The study of RG7112, an MDM2 antagonist, in 20 patients with MDM2-amplified liposarcoma showed significant activation of the P53 pathway, with P53 and P21 levels increasing by 4.86 and 3.48 times, respectively, after 8 days of treatment.

While RG7112 demonstrated the ability to inhibit tumor cell proliferation, resulting in one partial response and 14 cases of stable disease, it also caused adverse effects in all patients, with common issues including nausea and thrombocytopenia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of the MDM2 antagonist RG7112 on the P53 pathway in patients with MDM2-amplified, well-differentiated or dedifferentiated liposarcoma: an exploratory proof-of-mechanism study. Ray-Coquard, I., Blay, JY., Italiano, A., et al.[2022]

A genomic analysis of 56 liposarcoma samples revealed that while there were few gene mutations, over half of the samples exhibited gene amplifications, particularly of MDM2, CDK4, and receptor tyrosine kinases (RTKs).

In laboratory tests, combining CDK4 and IGF1R inhibitors effectively suppressed the growth of a well-differentiated liposarcoma cell line with IGF1R amplification, suggesting that this combination therapy could be a promising treatment for patients with these tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Frequent amplification of receptor tyrosine kinase genes in welldifferentiated/ dedifferentiated liposarcoma. Asano, N., Yoshida, A., Mitani, S., et al.[2018]

Citations

1. cancertherapyadvisor.com cancertherapyadvisor.com/reports/palbociclib-retifanlimab-liposarcoma/

Palbociclib Plus Retifanlimab Produces Deep, Durable ... The combination produced confirmed responses in 14% of patients and unconfirmed responses in 21%, and many of these responses were “deep and ...

2. annalsofoncology.org annalsofoncology.org/article/S0923-7534(24)03331-3/fulltext

1720MO A phase II study of palbociclib combined with the ... The DCR was 50% (95% CI 32.6 - 67.4%). Median PFS and OS were 2.2 (1.8 – not reached [NR]) and 24.8 months (24.8 – NR), respectively. Median DoR has not yet ...

3. withpower.com withpower.com/trial/phase-3-liposarcoma-5-2020-33652

Palbociclib + INCMGA00012 for Liposarcoma In a study of 61 patients with well-differentiated and dedifferentiated liposarcoma treated with palbociclib, the median progression-free survival was only 9.2 ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10253599/

Treatment of De-Differentiated Liposarcoma in the Era ... The median progression-free survival (PFS) was 17.9 weeks, and the estimated 12-week progression-free survival (PFS) was 66%. One patient (3%) ...

5. mycancergenome.org mycancergenome.org/content/clinical_trials/NCT04438824/

Clinical Trial: NCT04438824 The researchers are doing this study to find out whether combining the study drugs palbociclib and INCMGA00012 is an effective and safe ...

6. tandfonline.com tandfonline.com/doi/full/10.1080/1120009X.2025.2557678?src=

Palbociclib in liposarcoma: real-world multicenter data from ... Outcomes included progression-free survival (PFS), overall survival (OS), response, and safety. Results. Median age was 51 years; 38.1% had WDLPS and 61.9% ...