Rucaparib + Nivolumab for Leiomyosarcoma

Recruiting at 7 trial locations

Overseen By Sujana Movva, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Memorial Sloan Kettering Cancer Center

Must not be taking: Steroids, PARP inhibitors

Disqualifiers: CNS metastases, Autoimmune disease, HIV, 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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: 1

Duration: Up to 104 weeks (26 cycles)

20 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, if you are on chemotherapy or investigational therapies, you must have completed them at least 3 weeks before starting the study drugs. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the drug combination Rucaparib + Nivolumab for treating leiomyosarcoma?

There is no direct evidence supporting the effectiveness of Rucaparib + Nivolumab for leiomyosarcoma. However, targeting DNA damage repair pathways, which Rucaparib does, is considered promising for advanced leiomyosarcoma. Additionally, while PD-1 inhibitors like Nivolumab have shown limited success alone, combining them with other treatments is being explored for potential benefits. ^{1 2 3 4 5}

How is the drug combination of Rucaparib and Nivolumab unique for treating leiomyosarcoma?

The combination of Rucaparib and Nivolumab is unique for treating leiomyosarcoma because it targets DNA damage repair pathways and enhances the immune response, which are novel approaches compared to traditional chemotherapy options like anthracycline or gemcitabine-based regimens. This combination aims to increase the effectiveness of treatment by addressing the tumor's genetic and immune environment. ^{1 3 4 5 6}

What is the purpose of this trial?

The purpose of this study is to find out whether combining the study drugs rucaparib and nivolumab may be an effective treatment for advanced and/or metastatic LMS, and whether the study treatment works as well as the standard chemotherapy for this type of cancer.

Research Team

Sujana Movva, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Eligibility Criteria

Adults (18+) with advanced or metastatic Leiomyosarcoma who have had 1-3 prior systemic therapies can join this trial. They must not have used PARP inhibitors or PD-1/PD-L1 antibodies before, and should be recovered from previous treatments' side effects. Participants need functioning major organs, measurable disease, and no active infections or significant heart issues. Women of childbearing potential must test negative for pregnancy and agree to contraception.

Inclusion Criteria

My liver function tests are within the required range.

My LMS cannot be removed by surgery and has spread.

I finished any cancer treatments at least 3 weeks ago, and my side effects are mild.

Exclusion Criteria

I do not have any other cancer that needs treatment or could affect this trial.

Subjects expecting to have a child within the projected duration of the trial, starting with the pre-screening or screening visit through 6 months after the last dose of study treatment(s) for women or 7 months for men.

I have a weakened immune system due to conditions like HIV, Hepatitis B/C, or autoimmune diseases.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive rucaparib and nivolumab. Rucaparib is taken orally twice daily, and nivolumab is administered intravenously on day 1 of each 28-day cycle.

Up to 104 weeks (26 cycles)

1 visit every 4 weeks for nivolumab administration

Follow-up

Participants are monitored for safety and effectiveness after treatment, with re-staging scans every 8 weeks.

24 weeks

Treatment Details

Interventions

• Nivolumab
• Rucaparib

Trial Overview The study is testing the combination of Rucaparib (a drug that targets cancer cells) and Nivolumab (an immunotherapy) in patients with Leiomyosarcoma to see if it's more effective than standard chemotherapy. Patients will receive both drugs as part of their treatment regimen.

Participant Groups

Group I: Rucaparib in combination with Nivolumab Experimental Treatment 2 Interventions

One treatment cycle will consist of 28 days. Patients will receive rucaparib at 600 mg, orally, twice daily, continuously for 28 days. They will receive 480mg of nivolumab intravenously on day 1 of every four-week cycle. This is the recommended phase II dose of the combination therapy. Re-staging scans will be performed every 8 weeks. Treatment will be repeated until the patient develops progressive disease or unacceptable toxicity or for a maximum duration of 26 cycles as long as patients are receiving benefit from treatment, have not had disease progression, met any criteria for study withdrawal and are tolerating therapy.

Nivolumab is already approved in United States, European Union, Canada, Switzerland for the following indications:

Approved in United States as Opdivo for:

• Advanced or metastatic gastric cancer
• Gastroesophageal junction cancer
• Esophageal adenocarcinoma
• Melanoma
• Non-small cell lung cancer
• Renal cell carcinoma
• Hodgkin lymphoma
• Head and neck squamous cell carcinoma
• Urothelial carcinoma
• Colorectal cancer
• Hepatocellular carcinoma
• Esophageal squamous cell carcinoma

Approved in European Union as Opdivo for:

• Melanoma
• Non-small cell lung cancer
• Renal cell carcinoma
• Hodgkin lymphoma
• Head and neck squamous cell carcinoma
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Gastroesophageal junction cancer
• Esophageal adenocarcinoma

Approved in Canada as Opdivo for:

• Melanoma
• Non-small cell lung cancer
• Renal cell carcinoma
• Hodgkin lymphoma
• Head and neck squamous cell carcinoma
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Gastroesophageal junction cancer
• Esophageal adenocarcinoma

Approved in Switzerland as Opdivo for:

• Melanoma
• Non-small cell lung cancer
• Renal cell carcinoma
• Hodgkin lymphoma
• Head and neck squamous cell carcinoma
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Gastroesophageal junction cancer
• Esophageal adenocarcinoma

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

Clovis Oncology, Inc.

Industry Sponsor

Trials

65

Recruited

11,100+

Patrick J. Mahaffy

Clovis Oncology, Inc.

Chief Executive Officer since 2009

BA from Haverford College, MBA from Columbia University

Lindsey Rolfe

Clovis Oncology, Inc.

Chief Medical Officer since 2015

Specialist accreditation in pharmaceutical medicine

Bristol-Myers Squibb

Industry Sponsor

Trials

2,731

Recruited

4,127,000+

Headquarters

New York City, USA

Known For

Oncology & Cardiovascular

Top Products

Eliquis, Opdivo, Revlimid, Orencia

Christopher Boerner

Bristol-Myers Squibb

Chief Executive Officer since 2023

PhD in Business Administration from the Haas School of Business, University of California, Berkeley; BA in Economics and History from Washington University in St. Louis

Deepak L. Bhatt

Bristol-Myers Squibb

Chief Medical Officer since 2024

MD from Yale University; MSc in Clinical Epidemiology from the University of Pennsylvania

Findings from Research

In a study of 41 patients with advanced metastatic leiomyosarcoma, combining PD-1 inhibitors with pegylated liposomal doxorubicin (PLD) and dacarbazine (DTIC) resulted in a higher overall response rate (30% vs. 4.8%) compared to chemotherapy alone, indicating some potential for improved initial response.

However, there were no significant differences in progression-free survival (PFS) or overall survival (OS) between the two treatment groups, suggesting that while the combination may enhance response rates, it does not translate into longer survival benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of PD-1 inhibitors combined with pegylated liposomal doxorubicin and dacarbazine compared with liposomal doxorubicin and dacarbazine in advanced leiomyosarcoma patients: a retrospective, single-institutional cohort study. Tan, Z., Wang, X., Liu, J., et al.[2022]

Management of leiomyosarcoma (LMS) is highly individualized, depending on factors like tumor location, whether the disease is localized or metastatic, and the resectability of the tumor.

For patients with recurrent or metastatic LMS, systemic chemotherapy is typically the first-line treatment, with options including anthracycline or gemcitabine regimens, and emerging therapies may be guided by tumor genomics for more personalized treatment approaches.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Leiomyosarcoma: Does Location of Primary Help to Determine the Best Systemic Therapy Options? Novotny, JP., George, S.[2022]

References

1. China pubmed.ncbi.nlm.nih.gov

Efficacy of PD-1 inhibitors combined with pegylated liposomal doxorubicin and dacarbazine compared with liposomal doxorubicin and dacarbazine in advanced leiomyosarcoma patients: a retrospective, single-institutional cohort study. [2022]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Unmet Medical Needs and Future Perspectives for Leiomyosarcoma Patients-A Position Paper from the National LeioMyoSarcoma Foundation (NLMSF) and Sarcoma Patients EuroNet (SPAEN). [2021]

3. United States pubmed.ncbi.nlm.nih.gov

Leiomyosarcoma: Does Location of Primary Help to Determine the Best Systemic Therapy Options? [2022]

4. United States pubmed.ncbi.nlm.nih.gov

Immunotherapy with single agent nivolumab for advanced leiomyosarcoma of the uterus: Results of a phase 2 study. [2021]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Therapeutic advances in leiomyosarcoma. [2023]

6. United States pubmed.ncbi.nlm.nih.gov

Safety, Immunologic, and Clinical Activity of Durvalumab in Combination with Olaparib or Cediranib in Advanced Leiomyosarcoma: Results of the DAPPER Clinical Trial. [2023]