Cemiplimab + Palbociclib for Liposarcoma

Not currently recruiting at 204 trial locations

Overseen By Matthew Ingham, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Alliance for Clinical Trials in Oncology

Must not be taking: CDK4/6 inhibitors, Anti-PD-1/PD-L1

Disqualifiers: Active autoimmune, Uncontrolled illness, Pregnancy, 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: Up to 48 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new approach to treat advanced dedifferentiated liposarcoma, a cancer that can spread to nearby tissue or other body parts. Researchers compare the effects of two treatments: palbociclib alone versus a combination of palbociclib and cemiplimab. Palbociclib may stop cancer cells from growing, while cemiplimab, an antibody, could prevent cancer cells from spreading. People with advanced liposarcoma that cannot be surgically removed might be suitable for this trial. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications. However, you cannot use strong CYP3A inhibitors or inducers, and there is a required washout period (time without taking these medications) of 2 weeks for inhibitors and up to 5 weeks for inducers before re-registration.

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 liposarcoma and is generally well-tolerated. In studies involving 872 patients, common side effects included low white blood cell counts and tiredness. These side effects are expected and can often be managed.

Cemiplimab also maintains a good safety record. In patients with advanced skin cancer, common side effects included tiredness, muscle pain, rash, and diarrhea, with most being mild to moderate.

Overall, these findings suggest that both palbociclib and cemiplimab are generally well-tolerated. However, like any treatment, some risks remain. Prospective trial participants should discuss these risks with the trial team. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because they offer a novel approach to tackling liposarcoma. Unlike the standard chemotherapy options, such as doxorubicin, palbociclib is a CDK4/6 inhibitor that works by blocking proteins responsible for cell division, potentially slowing tumor growth. Cemiplimab, on the other hand, is an immune checkpoint inhibitor that helps the immune system recognize and attack cancer cells more effectively. This combination could provide a powerful one-two punch against liposarcoma, offering new hope for patients whose cancer has not responded well to traditional chemotherapy.

What evidence suggests that this trial's treatments could be effective for advanced dedifferentiated liposarcoma?

Research has shown that palbociclib, which participants in this trial may receive, effectively treats dedifferentiated liposarcoma, with patients experiencing an average of 9.2 months before the cancer worsens. In this trial, some participants will receive a combination of palbociclib and cemiplimab, a medicine that helps the immune system fight cancer. Early results suggest that adding cemiplimab to palbociclib could improve outcomes. Other studies have found that using cemiplimab with other treatments has improved survival rates. Together, these drugs might more effectively shrink or stop the growth of advanced liposarcoma than palbociclib alone. This combination is under study because it could provide a stronger attack against cancer cells. ^{5 6 7 8 9}

Are You a Good Fit for This Trial?

Adults with advanced dedifferentiated liposarcoma that's spread and can't be removed by surgery. They must have good organ function, no severe heart disease or active infections, and not be pregnant or nursing. People with certain autoimmune diseases or those needing high-dose steroids are excluded.

Inclusion Criteria

My hepatitis B viral load is undetectable with treatment.

I have at least one tumor that can be measured by specific criteria, and it has not been previously treated with radiation unless it has grown since then.

I can take care of myself and am up and about more than half of my waking hours.

Exclusion Criteria

I don't take more than 10 mg of prednisone or its equivalent daily.

I do not have any severe ongoing illnesses that would stop me from following the study's requirements.

I am not pregnant or breastfeeding and have a recent negative pregnancy test.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Safety Lead-In

A safety lead-in among 6 patients to confirm that the combination of palbociclib and cemiplimab is safe and tolerable

8 weeks

Treatment

Patients receive palbociclib alone or in combination with cemiplimab, with MRI or CT scans and blood sample collection throughout the trial

Up to 48 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 2 years

What Are the Treatments Tested in This Trial?

Interventions

• Cemiplimab
• Palbociclib

Trial Overview The trial is testing if adding Cemiplimab to Palbociclib improves treatment outcomes for advanced liposarcoma compared to Palbociclib alone. Participants will either receive the combination therapy or just Palbociclib, and their cancer's response will be monitored.

How Is the Trial Designed?

Group I: Arm II (palbociclib, cemiplimab) Experimental Treatment 6 Interventions

Patients receive palbociclib PO and cemiplimab IV on study. Patients undergo MRI or a CT scan throughout the trial. Patients may also undergo blood sample collection on study.

Group II: Arm I (palbociclib) Active Control 5 Interventions

Patients receive palbociclib PO on study. Patients will be allowed to cross over to Arm II following documentation of disease progression. Patients undergo MRI or CT scans throughout the trial. Patients may also undergo blood sample collection on study.

Cemiplimab is already approved in European Union, United States, Canada, Brazil for the following indications:

Approved in European Union as Libtayo for:

• Cutaneous squamous cell carcinoma (CSCC)
• Non-small cell lung cancer (NSCLC)

Approved in United States as Libtayo for:

• Cutaneous squamous cell carcinoma (CSCC)
• Basal cell carcinoma (BCC)
• Non-small cell lung cancer (NSCLC)

Approved in Canada as Libtayo for:

• Cutaneous squamous cell carcinoma (CSCC)
• Non-small cell lung cancer (NSCLC)

Approved in Brazil as Libtayo for:

• Cutaneous squamous cell carcinoma (CSCC)

Who Is Running the Clinical Trial?

Alliance for Clinical Trials in Oncology

Lead Sponsor

Trials

521

Recruited

224,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

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]

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]

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]

In the PALOMA-2 trial involving 666 postmenopausal women with ER+/HER2- advanced breast cancer, the combination of palbociclib and letrozole significantly improved progression-free survival compared to letrozole alone, with a hazard ratio of 0.58.

Neutropenia was the most common adverse event associated with palbociclib, occurring in 95.3% of patients, but it was mostly manageable through dose modifications and did not compromise treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Palbociclib with Letrozole in Postmenopausal Women with ER+/HER2- Advanced Breast Cancer: Hematologic Safety Analysis of the Randomized PALOMA-2 Trial. Diéras, V., Harbeck, N., Joy, AA., et al.[2020]

Erdafitinib, a pan-FGFR inhibitor, shows promise in treating dedifferentiated liposarcoma (DDLPS) by reducing cell viability and inducing apoptosis, particularly in tumors with high FGFR1 and/or FGFR4 expression, which correlates with poor prognosis.

Combining erdafitinib with the MDM2 antagonist RG7388 enhances its effectiveness, leading to improved tumor suppression in vitro and in vivo, and has shown disease stabilization in a patient with refractory DDLPS for 12 weeks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Novel Therapeutic Insights in Dedifferentiated Liposarcoma: A Role for FGFR and MDM2 Dual Targeting. Dadone-Montaudié, B., Laroche-Clary, A., Mongis, A., et al.[2020]

In a study involving 1723 women with HR+/HER2- advanced or metastatic breast cancer, palbociclib combined with aromatase inhibitors or fulvestrant showed low dose-reduction rates (18.9% and 12.3%, respectively), indicating good tolerability.

The treatment demonstrated favorable progression-free rates (PFR) at 12 months, with 88.1% for palbociclib + AI and 79.8% for palbociclib + fulvestrant, along with high survival rates (97.3% and 97.5%, respectively), suggesting its effectiveness in real-world clinical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-world treatment of patients with palbociclib for HR+/HER2-advanced/metastatic breast cancer: the Europe IRIS study. Mycock, K., Zhan, L., Hart, K., et al.[2022]

Palbociclib, when combined with fulvestrant, significantly improves progression-free survival in women with hormone receptor-positive, HER2-negative advanced breast cancer, showing a median PFS of 9.5 months compared to 4.6 months with placebo, based on a study of 521 women.

The safety profile of palbociclib includes common adverse reactions such as neutropenia and infections, which were observed in over 20% of patients, confirming its known side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval of Palbociclib in Combination with Fulvestrant for the Treatment of Hormone Receptor-Positive, HER2-Negative Metastatic Breast Cancer. Walker, AJ., Wedam, S., Amiri-Kordestani, L., et al.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05694871

NCT05694871 | Testing the Addition of Cemiplimab to ... The combination of these two drugs may be more effective in shrinking or stabilizing advanced dedifferentiated liposarcoma compared to palbociclib alone.

2. newsroom.regeneron.com newsroom.regeneron.com/news-releases/news-release-details/libtayor-cemiplimab-plus-chemotherapy-results-five-years

Libtayo® (cemiplimab) Plus Chemotherapy Results at Five ... The five-year probability of survival was 19.4% for the Libtayo combination versus 8.8% for chemotherapy. 8.2-month median progression-free ...

3. mdanderson.org mdanderson.org/patients-family/diagnosis-treatment/clinical-trials/clinical-trials-index/clinical-trials-detail.ID2023-1007.html

A randomized phase 2 trial with a safety lead-in to evaluate ... The combination of these two drugs may be more effective in shrinking or stabilizing advanced dedifferentiated liposarcoma compared to palbociclib alone.

4. withpower.com withpower.com/trial/phase-2-sarcoma-2023-bf5d0

Cemiplimab + Palbociclib for Liposarcoma Palbociclib has been used in patients with well-differentiated and dedifferentiated liposarcoma, showing a median progression-free survival of 9.2 months for ...

5. dana-farber.org dana-farber.org/clinical-trials/23-584

A RANDOMIZED PHASE 2 TRIAL WITH A SAFETY LEAD ... This phase II trial compares the effect of treatment with palbociclib alone to treatment with palbociclib plus cemiplimab for treating patients with ...

6. libtayohcp.com libtayohcp.com/cscc/safety

Safety profile - LIBTAYO® (cemiplimab-rwlc) LIBTAYO demonstrated a favorable safety profile in patients with advanced CSCC in clinical studies. 1 Adverse reactions in ≥10% of patients with mCSCC or ...

7. aetna.com aetna.com/cpb/medical/data/900_999/0942.html

Cemiplimab-rwlc (Libtayo) - Medical Clinical Policy Bulletins Results showed that 47.2 % of all patients treated with Libtayo had their tumors shrunk or disappeared. The majority of these patients had ongoing responses at ...

8. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2022/761097s014lbl.pdf

LIBTAYO® (cemiplimab-rwlc) injection, for intravenous use In this pooled safety population, the most common adverse reactions (≥15%) were musculoskeletal pain, fatigue, rash, and diarrhea. The most common Grade 3-4 ...

9. regeneron.com regeneron.com/downloads/libtayo_fpi.pdf

LIBTAYO® Full Prescribing Information In this pooled safety population, the most common adverse reactions. ("15%) were fatigue, musculoskeletal pain, rash, diarrhea, and anemia. The most common ...