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

Trial Summary

What is the purpose of this trial?

This study is being done to find out whether the study drug Retifanlimab, a monoclonal antibody against the PD-1 protein, combined with gemcitabine and docetaxel, is a safe and effective treatment for your disease. Gemcitabine and docetaxel are chemotherapy drugs that are commonly used to treat soft tissue sarcoma. Retifanlimab is an experimental drug that boosts the immune system's ability to fight cancer cells. The study researchers think that Retifanlimab may help gemcitabine and docetaxel work better against soft tissue sarcoma that is either locally advanced or has spread beyond its original location (metastasized), and it cannot be removed with surgery (unresectable).

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.

What data supports the effectiveness of the drug combination Retifanlimab + Chemotherapy for Soft Tissue Sarcoma?

Research shows that the combination of gemcitabine and docetaxel, which are part of the chemotherapy regimen, is effective for treating advanced soft tissue sarcoma. This combination has shown activity in patients with metastatic sarcomas, suggesting it could be beneficial in this context. ^{1 2 3 4 5}

Is the combination of Retifanlimab, Gemcitabine, and Docetaxel safe for humans?

The combination of Gemcitabine and Docetaxel has been used in patients with soft tissue sarcoma, and while it shows some activity, it can cause expected chemotherapy-related side effects. These side effects were not severe enough to stop treatment in the studies reviewed. ^{2 4 5 6 7}

What makes the drug combination of Retifanlimab, Docetaxel, and Gemcitabine unique for treating soft tissue sarcoma?

The combination of Retifanlimab with Docetaxel and Gemcitabine is unique because Retifanlimab is an immune checkpoint inhibitor that may enhance the body's immune response against cancer cells, potentially offering a novel mechanism of action compared to traditional chemotherapy alone, which primarily targets cancer cells directly. ^{1 2 4 5 8}

Research Team

Evan Rosenbaum, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Gemcitabine Plus Anlotinib Is Effective and Safe Compared to Gemcitabine Plus Docetaxel in Advanced Soft Tissue Sarcoma. [2022]

2. England pubmed.ncbi.nlm.nih.gov

Phase IB study of the combination of docetaxel, gemcitabine, and bevacizumab in patients with advanced or recurrent soft tissue sarcoma: the Axtell regimen. [2023]

3. Korea (South) pubmed.ncbi.nlm.nih.gov

Gemcitabine and Docetaxel Combination for Advanced Soft Tissue Sarcoma: A Nationwide Retrospective Study. [2022]

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

Randomized phase II study of gemcitabine and docetaxel compared with gemcitabine alone in patients with metastatic soft tissue sarcomas: results of sarcoma alliance for research through collaboration study 002 [corrected]. [2022]

5. England pubmed.ncbi.nlm.nih.gov

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

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

Treatment of relapsed/refractory pediatric sarcomas with gemcitabine and docetaxel. [2022]

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

Poor treatment outcomes with palliative gemcitabine and docetaxel chemotherapy in advanced and metastatic synovial sarcoma. [2022]

8. Egypt pubmed.ncbi.nlm.nih.gov

Phase II Trial of Gemcitabine and Docetaxel with Bevacizumab in Soft Tissue Sarcoma. [2020]