Retifanlimab + Chemotherapy for Soft Tissue Sarcoma

Recruiting at 1 trial location

Overseen By Sandra D'Angelo, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Memorial Sloan Kettering Cancer Center

Must not be taking: Immunosuppressants, Antiretrovirals

Disqualifiers: Cardiovascular disease, Autoimmune disease, HIV, others

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

Compensation: Varies

Number of Visits: 3

Duration: 105 weeks

98 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether combining Retifanlimab, an experimental drug that aids the immune system in fighting cancer, with two common chemotherapy drugs, gemcitabine and docetaxel, can effectively treat soft tissue sarcoma. Soft tissue sarcoma is a type of cancer that can be advanced, spreading, and non-removable by surgery. The trial targets individuals with this cancer who have not received systemic therapy before. Participants will receive the combination treatment in varied doses to determine the safest and most effective use of these drugs together. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot participate if you are currently using immunosuppressive medication, except for certain types like low-dose steroids or specific premedications.

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

Research has shown that Retifanlimab treats certain cancers, such as Merkel cell carcinoma, and is generally well-tolerated. However, it remains under close monitoring, so new safety information may emerge.

For gemcitabine, studies in patients with soft tissue sarcoma have demonstrated that it can cause a drop in blood cell counts, known as myelosuppression. Severe side effects occurred in about 80% of patients when combined with other drugs.

Docetaxel has been an approved cancer treatment for some time. It is known to cause side effects like changes in blood cells and allergic reactions. Serious side effects have been reported but can be managed with medical care.

Overall, these treatments have been used in various situations with known side effects, but using them with Retifanlimab remains experimental. Discuss any concerns with the study team or your doctor. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard treatments for soft tissue sarcoma, which often involve surgery, radiation, and traditional chemotherapy, this combination of Retifanlimab with chemotherapy is unique because Retifanlimab is an immune checkpoint inhibitor. Researchers are particularly excited about Retifanlimab because it targets the PD-1 pathway, an approach that can help the immune system recognize and attack cancer cells more effectively. Additionally, the combination therapy aims to enhance the efficacy of chemotherapy, potentially offering better outcomes for patients who have progressed on previous treatments. This innovative approach could provide a new line of defense against advanced sarcomas, offering hope for improved survival rates and quality of life.

What evidence suggests that this trial's treatments could be effective for soft tissue sarcoma?

Studies have shown that using gemcitabine and docetaxel together can improve outcomes by about 20% in patients with metastatic soft tissue sarcoma. In this trial, participants will receive a combination of gemcitabine and docetaxel, with some treatment arms including Retifanlimab. Retifanlimab, a monoclonal antibody, targets a protein called PD-1, which helps cancer cells evade the immune system. In other cancers, such as advanced anal cancer, Retifanlimab delayed disease progression for an average of 9.3 months when combined with chemotherapy. Although Retifanlimab is still under investigation for soft tissue sarcoma in this trial, early research in other cancers suggests it might work well with gemcitabine and docetaxel. ^{6 7 8 9 10}

Who Is on the Research Team?

Evan Rosenbaum, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Are You a Good Fit for This Trial?

Adults over 18 with advanced soft tissue sarcoma that can't be surgically removed may join this trial. They should have no prior systemic therapy, controlled hepatitis if present, and good organ function. Pregnant or breastfeeding women, those planning to conceive soon, and individuals with uncontrolled HIV or severe allergies to monoclonal antibodies cannot participate.

Inclusion Criteria

I have not had any systemic therapy before.

I have chronic HBV or HCV but it's under control.

Negative serum pregnancy test in women of childbearing potential

Exclusion Criteria

I am currently on medication for an infection.

I haven't had symptoms of autoimmune disease in the last 2 years, except for conditions treated with replacement therapies like insulin.

I received initial cancer treatment over a year ago.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive gemcitabine and docetaxel for 6 cycles, with Retifanlimab added from cycle 2, continuing until unacceptable toxicity, disease progression, or completion of 35 cycles

105 weeks

Visits every 3 weeks +/- 3 days

Follow-up

Participants are monitored for safety and effectiveness after treatment

24 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Docetaxel
• Gemcitabine
• Retifanlimab

Trial Overview The trial tests Retifanlimab combined with chemotherapy drugs Gemcitabine and Docetaxel in patients with advanced soft tissue sarcoma. Researchers believe Retifanlimab might enhance the immune system's response when used alongside these chemotherapies.

How Is the Trial Designed?

Group I: Vascular Sarcoma Experimental Treatment 3 Interventions

After the RP2D is determined, 5 histology-specific cohorts (10 patients each), including UPS/MFS, LPS, LMS, vascular sarcoma, and other STS, will open for enrollment. Patients will be treated with the RP2D of gemcitabine/docetaxel (when administered in combination with Retifanlimab) for cycle 1, with Retifanlimab added on cycle 2 day 1 at a flat dose of 375 mg. Gemcitabine/docetaxel will continue for 5 additional cycles (total of 6 cycles), after which treatment with Retifanlimab will continue until unacceptable toxicity, disease progression, or the completion of 35 cycles (105 weeks) of Retifanlimab treatment. All visits are to be done +/-3 days of the scheduled timepoints.

Group II: Undifferentiated Pleomorphic Sarcoma/Myxofibrosarcoma Experimental Treatment 3 Interventions

(UPS/MFS) After the RP2D is determined, 5 histology-specific cohorts (10 patients each), including UPS/MFS, LPS, LMS, vascular sarcoma, and other STS, will open for enrollment. Patients will be treated with the RP2D of gemcitabine/docetaxel (when administered in combination with Retifanlimab) for cycle 1, with Retifanlimab added on cycle 2 day 1 at a flat dose of 375 mg. Gemcitabine/docetaxel will continue for 5 additional cycles (total of 6 cycles), after which treatment with Retifanlimab will continue until unacceptable toxicity, disease progression, or the completion of 35 cycles (105 weeks) of Retifanlimab treatment. All visits are to be done +/-3 days of the scheduled timepoints.

Group III: Phase I: Safety Run-In / Dose Level 0 Experimental Treatment 3 Interventions

A safety run-in (dose level 0 in Table 1, below) will be performed and enroll 6 patients with advanced high-grade sarcoma who are treatment naïve. Cycle one will consist of gemcitabine plus docetaxel at the institution's standard dose and schedule: 900 mg/m2 of gemcitabine on days 1 and 8, and 75 mg/m2 of docetaxel on day 8. Intravenous Retifanlimab at a flat dose of 210 mg will be administered every 3 weeks starting on C2D1 for a total of two cycles (cycles 2 and 3). All visits are to be done +/-3 days of the scheduled timepoints.

Group IV: Phase I: Dose De-escalation Level 1 Experimental Treatment 3 Interventions

If ≤ 1 patient out of 6 at dose level 0 has a dose-limiting toxicity during this safety run-in, then the dose de-escalation portion of the protocol will commence. Dose Level 1: Retifanlimab (Day 1) - 375 mg (flat dose) Gemcitabine (Days 1 and 8) - 900 mg/m2 Docetaxel (Day 8) - 75 mg/m2 All visits are to be done +/-3 days of the scheduled timepoints.

Group V: Phase I: Dose De-escalation Level -2 Experimental Treatment 3 Interventions

Dose Level -2: Retifanlimab (Day 1) - 375 mg (flat dose) Gemcitabine (Days 1 and 8) - 675 mg/m2 Docetaxel (Day 8) - 50 mg/m2 All visits are to be done +/-3 days of the scheduled timepoints.

Group VI: Phase I: Dose De-escalation Level -1 Experimental Treatment 3 Interventions

Dose Level -1: Retifanlimab (Day 1) - 375 mg (flat dose) Gemcitabine (Days 1 and 8) - 750 mg/m2 Docetaxel (Day 8) - 60 mg/m2 All visits are to be done +/-3 days of the scheduled timepoints.

Group VII: Other Soft tissue sarcoma/STS Experimental Treatment 3 Interventions

After the RP2D is determined, 5 histology-specific cohorts (10 patients each), including UPS/MFS, LPS, LMS, vascular sarcoma, and other STS, will open for enrollment. Patients will be treated with the RP2D of gemcitabine/docetaxel (when administered in combination with Retifanlimab) for cycle 1, with Retifanlimab added on cycle 2 day 1 at a flat dose of 375 mg. Gemcitabine/docetaxel will continue for 5 additional cycles (total of 6 cycles), after which treatment with Retifanlimab will continue until unacceptable toxicity, disease progression, or the completion of 35 cycles (105 weeks) of Retifanlimab treatment. All visits are to be done +/-3 days of the scheduled timepoints.

Group VIII: Liposarcoma/LPS Experimental Treatment 3 Interventions

After the RP2D is determined, 5 histology-specific cohorts (10 patients each), including UPS/MFS, LPS, LMS, vascular sarcoma, and other STS, will open for enrollment. Patients will be treated with the RP2D of gemcitabine/docetaxel (when administered in combination with Retifanlimab) for cycle 1, with Retifanlimab added on cycle 2 day 1 at a flat dose of 375 mg. Gemcitabine/docetaxel will continue for 5 additional cycles (total of 6 cycles), after which treatment with Retifanlimab will continue until unacceptable toxicity, disease progression, or the completion of 35 cycles (105 weeks) of Retifanlimab treatment. All visits are to be done +/-3 days of the scheduled timepoints.

Group IX: Leiomyosarcoma/LMS Experimental Treatment 3 Interventions

After the RP2D is determined, 5 histology-specific cohorts (10 patients each), including UPS/MFS, LPS, LMS, vascular sarcoma, and other STS, will open for enrollment. Patients will be treated with the RP2D of gemcitabine/docetaxel (when administered in combination with Retifanlimab) for cycle 1, with Retifanlimab added on cycle 2 day 1 at a flat dose of 375 mg. Gemcitabine/docetaxel will continue for 5 additional cycles (total of 6 cycles), after which treatment with Retifanlimab will continue until unacceptable toxicity, disease progression, or the completion of 35 cycles (105 weeks) of Retifanlimab treatment. All visits are to be done +/-3 days of the scheduled timepoints.

Group X: Advanced sarcoma who have progressed on prior treatment Experimental Treatment 1 Intervention

Participants will have advanced sarcoma who have progressed on prior treatment and have an immune-enriched/non-fibrotic TME

Docetaxel is already approved in United States, European Union, Canada, Japan for the following indications:

Approved in United States as Taxotere for:

• Breast Cancer
• Non-small Cell Lung Cancer
• Gastric Cancer
• Head and Neck Cancer
• Prostate Cancer

Approved in European Union as Taxotere for:

• Breast Cancer
• Non-small Cell Lung Cancer
• Gastric Cancer
• Head and Neck Cancer
• Prostate Cancer

Approved in Canada as Taxotere for:

• Breast Cancer
• Non-small Cell Lung Cancer
• Gastric Cancer
• Head and Neck Cancer
• Prostate Cancer

Approved in Japan as Taxotere for:

• Breast Cancer
• Non-small Cell Lung Cancer
• Gastric Cancer
• Head and Neck Cancer
• Prostate Cancer

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

The combination of gemcitabine and docetaxel has shown effectiveness in treating metastatic sarcomas, particularly in leiomyosarcoma and undifferentiated high-grade pleomorphic sarcoma, expanding treatment options for oncologists.

There is evidence suggesting that the combination may work synergistically, especially since docetaxel alone has a low response rate, indicating that using both drugs together could enhance treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gemcitabine and docetaxel in metastatic sarcoma: past, present, and future. Maki, RG.[2022]

In a study of 10 pediatric patients with relapsed or refractory sarcomas, the combination of gemcitabine and docetaxel showed significant antitumor activity, with 50% of patients achieving a complete or partial response.

The treatment was well-tolerated, with only mild toxicities reported, and allowed for a median duration of response of 10 months, indicating a good quality of life for the patients during therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of relapsed/refractory pediatric sarcomas with gemcitabine and docetaxel. Mora, J., Cruz, CO., Parareda, A., et al.[2022]

In a review of 21 patients with synovial sarcoma treated with gemcitabine/docetaxel chemotherapy, the treatment showed a low response rate of only 5% and a median progression-free survival of just 2 months, indicating limited efficacy.

Despite the expected toxicities associated with this chemotherapy combination, treatment was tolerated without discontinuation due to toxicity, but the authors recommend that this regimen should not be used outside of clinical trials for this patient group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Poor treatment outcomes with palliative gemcitabine and docetaxel chemotherapy in advanced and metastatic synovial sarcoma. Pender, A., Davis, EJ., Chauhan, D., et al.[2022]

Citations

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Phase II study with docetaxel (Taxotere) in advanced soft ... Background: Current regimens for treatment of distant metastases of soft tissues sarcomas result in response rates of about 25%. Therefore the search for ...

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Phase II study with Docetaxel (Taxotere®) in advanced soft ... Conclusion: Taxotere has activity in adult soft tissue sar- coma in second line, warranting studies on first line efficacy. Key words: docetaxel, soft tissue ...

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Taxotere (docetaxel) Label - accessdata.fda.gov Included in this table are safety data for a total of 176 patients with non-small cell lung carcinoma and a history of prior treatment with platinum-based ...

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