Retifanlimab (Anti-PD-1 Antibody) With Gemcitabine and Docetaxel in Patients With Advanced Soft Tissue Sarcoma

NCT04577014 | Recruiting Phase 1 FDA Drug

• 1 other identifier: 20-316
• Study Type: interventional
• Target: 98
• Locations: 1 country
• Sites: 1

Brief Summary

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).

Conditions

Sarcoma,Soft Tissue; Soft Tissue Sarcoma Adult; Soft Tissue Sarcoma; Sarcoma

Keywords

soft tissue sarcoma; locally advanced soft tissue sarcoma; unresectable soft tissue sarcoma; metastasized soft tissue sarcoma; sarcoma; Retifanlimab; 20-316; Memorial Sloan Kettering Cancer Center

Outcome Measures

Primary Outcomes (1)

• Phase II: proportion of patients that are progression-free at 24 weeks by RECIST v1.1

  The primary objective of the phase II portion of this study is to determine the proportion of patients that are progression-free at 24 weeks by RECIST v1.1. Progressive disease is declared when there is an increase in sum of target disease ≥ 20%, stable disease when the change is \> -30% and ≤ 20%, partial response when there is a decrease in sum of target disease ≥ 30%, and complete response when all lesions have disappeared or all lesions have disappeared and all nodal disease is \< 10 mm each.

  24 weeks

Study Arms (10)

Phase I: Safety Run-In / Dose Level 0

EXPERIMENTAL

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.

Drug: Retifanlimab; Drug: Gemcitabine; Drug: Docetaxel

Phase I: Dose De-escalation Level 1

EXPERIMENTAL

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.

Drug: Retifanlimab; Drug: Gemcitabine; Drug: Docetaxel

Phase I: Dose De-escalation Level -1

EXPERIMENTAL

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.

Drug: Retifanlimab; Drug: Gemcitabine; Drug: Docetaxel

Phase I: Dose De-escalation Level -2

EXPERIMENTAL

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.

Drug: Retifanlimab; Drug: Gemcitabine; Drug: Docetaxel

Undifferentiated Pleomorphic Sarcoma/Myxofibrosarcoma

EXPERIMENTAL

(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.

Drug: Retifanlimab; Drug: Gemcitabine; Drug: Docetaxel

Liposarcoma/LPS

EXPERIMENTAL

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.

Drug: Retifanlimab; Drug: Gemcitabine; Drug: Docetaxel

Leiomyosarcoma/LMS

EXPERIMENTAL

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.

Drug: Retifanlimab; Drug: Gemcitabine; Drug: Docetaxel

Vascular Sarcoma

EXPERIMENTAL

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.

Drug: Retifanlimab; Drug: Gemcitabine; Drug: Docetaxel

Other Soft tissue sarcoma/STS

EXPERIMENTAL

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.

Drug: Retifanlimab; Drug: Gemcitabine; Drug: Docetaxel

Advanced sarcoma who have progressed on prior treatment

EXPERIMENTAL

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

Drug: Retifanlimab

Interventions

Retifanlimab DRUG

Phase I: Dose Level 1 - 375 mg (flat dose) Dose Level 0 - 210 mg (flat dose) Dose Level -1 - 375 mg (flat dose) Dose Level -2 - 375 mg (flat dose) Phase II: 375 mg (flat dose)

Also known as: INCMGA00012

Advanced sarcoma who have progressed on prior treatment; Leiomyosarcoma/LMS; Liposarcoma/LPS; Other Soft tissue sarcoma/STS; Phase I: Dose De-escalation Level -1; Phase I: Dose De-escalation Level -2; Phase I: Dose De-escalation Level 1; Phase I: Safety Run-In / Dose Level 0; Undifferentiated Pleomorphic Sarcoma/Myxofibrosarcoma; Vascular Sarcoma

Gemcitabine DRUG

Phase I: Dose Level 1 - 900 mg/m2 Dose Level 0 - 900 mg/m2 Dose Level -1 - 750 mg/m2 Dose Level -2 - 675 mg/m2 The dose level with ≤ 1 DLT seen per patients will be declared the RP2D. Phase II: Participants 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 375mg. Gemcitabine/docetaxel will continue for 5 additional cycles (total of 6 cycles),

Leiomyosarcoma/LMS; Liposarcoma/LPS; Other Soft tissue sarcoma/STS; Phase I: Dose De-escalation Level -1; Phase I: Dose De-escalation Level -2; Phase I: Dose De-escalation Level 1; Phase I: Safety Run-In / Dose Level 0; Undifferentiated Pleomorphic Sarcoma/Myxofibrosarcoma; Vascular Sarcoma

Docetaxel DRUG

Phase I: Dose Level 1 - 75 mg/m2 Dose Level 0 - 75 mg/m2 Dose Level -1 - 60 mg/m2 Dose Level -2 - 50 mg/m2 The dose level with ≤ 1 DLT seen per patients will be declared the RP2D. Phase II: Participants 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 375mg. Gemcitabine/docetaxel will continue for 5 additional cycles (total of 6 cycles),

Leiomyosarcoma/LMS; Liposarcoma/LPS; Other Soft tissue sarcoma/STS; Phase I: Dose De-escalation Level -1; Phase I: Dose De-escalation Level -2; Phase I: Dose De-escalation Level 1; Phase I: Safety Run-In / Dose Level 0; Undifferentiated Pleomorphic Sarcoma/Myxofibrosarcoma; Vascular Sarcoma

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of metastatic or locally advanced and unresectable high-grade soft tissue sarcoma. Unresectable is defined as:
• primary tumor cannot be safely removed surgically, or
• primary tumor would benefit from systemic therapy prior to a surgical approach
• Be willing and able to provide written informed consent
• Must consent to mandatory tumor biopsy (if deemed safe and feasible) for research studies at screening, if archival tissue is not available, and at C1D15, C3D15.
• Age ≥ 18 years
• ECOG performance status ≤ 1
• Presence of measurable disease per RECIST v1.1
• Target lesions must not be chosen from a previously irradiated field unless there has been radiographically and/or pathologically documented tumor progression in that lesion prior to enrollment.

You may not qualify if:

• Negative serum pregnancy test in women of childbearing potential
• Patients with chronic HBV (HBsAg-positive with undetectable or low HBV DNA and normal ALT, or HBsAg-negative with anti-HBc-positive serology) and HCV (completed curative antiviral treatment with HCV viral load below the limit of quantification) may be eligible
• Patients with HBV should be treated with suppressive antiviral therapy prior to enrollment
• Patients with HCV must have completed curative therapy and have negative HCV viral load
• Adequate organ function, as defined in Table 2:
• Hematological Absolute neutrophil count (ANC): ≥ 1,500 /mcL Platelets: ≥ 75,000 / mcL Hemoglobin: ≥ 9g/dL or ≥ 5.6 mmol/L
• Renal Serum creatinine: ≤ 1.5 X upper limit of normal (ULN) OR Measured or calculated creatinine clearance: ≥ 60 mL/min for patient with creatinine levels \> 1.5 X institutional ULN (GFR can also be used in place of creatinine orCrCl)
• Hepatic Serum total bilirubin: ≤ 1.5 X ULN OR Direct bilirubin ≤ ULN for patients with total bilirubin levels \> 1.5 ULN except patients with Gilbert's disease (≤ 3x ULN) AST (SGOT) and ALT (SGPT): ≤ 2.5 X ULN OR ≤ 5 X ULN for patients with liver metastases
• Received any systemic therapy in the advanced or metastatic setting
• Adjuvant or neoadjuvant therapies received ≥ 1 year prior to enrollment are permitted
• Unstable or deteriorating cardiovascular disease within the previous 6 months, including:
• Unstable angina or myocardial infarction
• CVA/stroke
• New York Heart Association \[NYHA\] Class III or IV congestive heart failure
• Uncontrolled clinically significant arrhythmias

Sponsors & Collaborators

• Memorial Sloan Kettering Cancer Center: lead
• Incyte Corporation: collaborator

Study Sites (1)

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

RECRUITING

Related Links

• Memorial Sloan Kettering Cancer Center

MeSH Terms

Conditions

Sarcoma

Interventions

Gemcitabine; Docetaxel

Condition Hierarchy (Ancestors)

Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes

Study Officials

• Sandra D'Angelo, MD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Sandra D'Angelo, MD

CONTACT

646-888-4159; zzPDL_MED_Sarcoma_Clinical_Trials@mskcc.org

William Tap, MD

CONTACT

646-888-4163; zzPDL_MED_Sarcoma_Clinical_Trials@mskcc.org

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 30, 2020
• First Posted: October 6, 2020
• Study Start: September 29, 2020
• Primary Completion (Estimated): September 29, 2026
• Study Completion (Estimated): September 29, 2026
• Last Updated: April 14, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share

Locations

US (1)