CDK4/6 Inhibitor for Liposarcoma

No longer recruiting at 9 trial locations

Overseen By Dinah M Jaunakais, M.Ed.

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Shanghai Pharma Biotherapeutics USA Inc.

Must not be taking: CYP3A4 inhibitors, inducers

Disqualifiers: CDK4 negative, CNS metastases, 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: 19

Duration: 36 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the safety and effectiveness of a new drug, SPH4336, a CDK4/6 inhibitor, for treating certain types of liposarcoma, a kind of tumor. Researchers aim to assess the drug's effectiveness against tumors and its behavior in the body. It is open to participants with dedifferentiated or well-differentiated/dedifferentiated liposarcomas that have worsened after other treatments. Participants should have undergone no more than three previous treatments and show signs of recent cancer progression, such as new tumors. 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 requires that you do not take strong CYP3A4 inhibitors or inducers at the start of the study. If you are on such medications, you may need to stop them before participating.

Is there any evidence suggesting that SPH4336 is likely to be safe for humans?

Previous studies have shown SPH4336 to be generally safe for participants. Research indicates that people tolerated doses between 50 and 600 mg daily well, with most not experiencing serious side effects. The current trial uses a 400 mg dose, deemed suitable for further testing. Earlier studies identified no major safety issues with SPH4336, although it was less effective in treating liposarcoma than expected. Overall, based on these studies, SPH4336 appears safe for human use. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for liposarcoma, which often involve chemotherapy and radiation, SPH4336 acts by inhibiting CDK4/6, a key protein involved in cell division. Researchers are excited about SPH4336 because it targets the cancer cells more precisely, potentially leading to fewer side effects and better outcomes. Additionally, its oral administration as a daily tablet offers a more convenient option compared to traditional intravenous therapies.

What evidence suggests that SPH4336 might be an effective treatment for liposarcoma?

Research has shown that SPH4336, a drug that blocks certain proteins, holds potential for treating some cancers. In an earlier study, one patient's cancer shrank for about six months, and nearly 60% of patients experienced either disease stabilization or improvement. Although the drug has shown success with some cancers, its effectiveness for liposarcoma remains uncertain. This trial will specifically assess SPH4336's effectiveness for liposarcoma. Overall, SPH4336 is considered safe and promising, but further studies are needed to determine its efficacy specifically for liposarcoma. ^{1 2 3 6 7}

Who Is on the Research Team?

Kenneth W Locke, PhD

Principal Investigator

Shanghai Pharma Biotherapeutics USA Inc.

Are You a Good Fit for This Trial?

Adults over 18 with advanced liposarcomas, either dedifferentiated or well-differentiated/dedifferentiated, who have had no more than three prior treatments and show tumor progression. Participants must be in good physical condition (ECOG 0 or 1), not have major organ dysfunction, agree to use effective contraception, and provide tissue samples for research.

Inclusion Criteria

My sarcoma is confirmed and has spread or is advanced.

I am fully active or can carry out light work.

I have had 3 or fewer previous cancer treatments.

Exclusion Criteria

I have been treated with a CDK4/6 inhibitor before.

I currently have COVID-19.

Any other medical or psychiatric condition, or laboratory abnormality that would result in an unacceptable risk with study participation

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Safety Lead-in

Initial 10 subjects are evaluated for safety after completing at least 1 cycle

4 weeks

1 visit (in-person)

Treatment

Participants receive SPH4336 orally once daily in 28-day cycles

36 weeks

Visits every 6 weeks for tumor assessments

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 weeks

Visits every 12 weeks

What Are the Treatments Tested in This Trial?

Interventions

• SPH4336

Trial Overview The trial is testing SPH4336, a selective enzyme blocker designed to treat specific types of liposarcomas. It's an open-label study meaning everyone gets the drug; there's no placebo group. The focus is on safety, how the body processes the drug (pharmacokinetics), and its initial effectiveness against tumors.

How Is the Trial Designed?

Group I: SPH4336 Experimental Treatment 1 Intervention

400 mg (2 - 200 mg tablets) PO QD

Who Is Running the Clinical Trial?

Shanghai Pharma Biotherapeutics USA Inc.

Lead Sponsor

Trials

2

Recruited

40+

Published Research Related to This Trial

In a phase 2 clinical trial involving 60 patients with advanced well-differentiated or dedifferentiated liposarcomas (WD/DDLS), palbociclib at a new dose of 125 mg daily for 21 days every 28 days resulted in a progression-free survival (PFS) rate of 57.2% at 12 weeks, indicating its efficacy in this patient population.

The treatment was associated with manageable hematologic toxic effects, primarily neutropenia, suggesting that this dosing schedule may be safer compared to the previously tested regimen of 200 mg for 14 days.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Progression-Free Survival Among Patients With Well-Differentiated or Dedifferentiated Liposarcoma Treated With CDK4 Inhibitor Palbociclib: A Phase 2 Clinical Trial. Dickson, MA., Schwartz, GK., Keohan, ML., 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. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.e15107

First-in-human phase 1 study of SPH4336, a novel cyclin ... Of the 27 evaluable patients, 1 patient achieved partial response lasting 169 days, and disease control rate was 59.3% (95% CI: 38.8%-77.6%).

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40586764/

Phase I trial of SPH4336, a novel cyclin-dependent kinase ... SPH4336 demonstrated an acceptable safety profile and dose-dependent plasma exposure in patients with various advanced solid tumors.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT05580588

Open-Label Study of the CDK4/6 Inhibitor SPH4336 in ... Although no safety issues with SPH4336 were identified, efficacy in liposarcoma patient was less than anticipated. Open-Label Study of the CDK4/​6 Inhibitor ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12207880/

Phase I trial of SPH4336, a novel cyclin-dependent kinase ... Preliminary efficacy showed a confirmed partial response in a patient with breast cancer and an overall disease control rate of 59.3%. PFS ...

5. tipranks.com tipranks.com/news/company-announcements/shanghai-pharmaceuticals-new-study-on-sph4336-and-cadonilimab-a-potential-game-changer-in-cancer-treatment

Shanghai Pharmaceuticals' New Study on SPH4336 and ... ' The study aims to assess the effectiveness and safety of SPH4336, alone or combined with Cadonilimab, in treating advanced solid tumors, ...

6. academic.oup.com academic.oup.com/oncolo/article/30/6/oyaf077/8178499

Phase I trial of SPH4336, a novel cyclin-dependent kinase 4/6 ... This study demonstrates that SPH4336 is well tolerated and safe within the dose range from 50 to 600 mg QD.

7. delta.larvol.com delta.larvol.com/Products/?ProductId=341b4b4f-16a9-4bec-a737-9d32eace354a

SPH4336 / Shanghai Pharma Shanghai Pharmaceuticals' SPH4336 tablets were approved for clinical trials, and they will work together with osimertinib to fight against advanced KRAS mutant ...