Clinical Trials /

INCMGA00012 (Anti-PD-1 Antibody) With Gemcitabine and Docetaxel in Patients With Advanced Soft Tissue Sarcoma

NCT04577014

Description:

This study is being done to find out whether the study drug INCMGA00012, 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. INCMGA00012 is an experimental drug that boosts the immune system's ability to fight cancer cells. The study researchers think that INCMGA00012 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).

Related Conditions:
  • Leiomyosarcoma
  • Liposarcoma
  • Soft Tissue Sarcoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: INCMGA00012 With Gemcitabine and Docetaxel in People With Advanced Soft Tissue Sarcoma
  • Official Title: Phase I/II Study of Gemcitabine and Docetaxel Combined With Immune Checkpoint Blockade (INCMGA00012) in Patients With Advanced Soft Tissue Sarcoma

Clinical Trial IDs

  • ORG STUDY ID: 20-316
  • NCT ID: NCT04577014

Conditions

  • Soft Tissue Sarcoma
  • Sarcoma,Soft Tissue
  • Sarcoma
  • Soft Tissue Sarcoma Adult

Interventions

DrugSynonymsArms
INCMGA00012Leiomyosarcoma/LMS
GemcitabineLeiomyosarcoma/LMS
DocetaxelLeiomyosarcoma/LMS

Purpose

This study is being done to find out whether the study drug INCMGA00012, 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. INCMGA00012 is an experimental drug that boosts the immune system's ability to fight cancer cells. The study researchers think that INCMGA00012 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).

Trial Arms

NameTypeDescriptionInterventions
Phase I: Safety Run-In / Dose Level 0ExperimentalA 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 INCMGA00012 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).
  • INCMGA00012
  • Gemcitabine
  • Docetaxel
Phase I: Dose De-escalation Level 1ExperimentalIf ≤ 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: INCMGA00012 (Day 1) - 375 mg (flat dose) Gemcitabine (Days 1 and 8) - 900 mg/m2 Docetaxel (Day 8) - 75 mg/m2
  • INCMGA00012
  • Gemcitabine
  • Docetaxel
Phase I: Dose De-escalation Level -1ExperimentalDose Level -1: INCMGA00012 (Day 1) - 375 mg (flat dose) Gemcitabine (Days 1 and 8) - 750 mg/m2 Docetaxel (Day 8) - 60 mg/m2
  • INCMGA00012
  • Gemcitabine
  • Docetaxel
Phase I: Dose De-escalation Level -2ExperimentalDose Level -2: INCMGA00012 (Day 1) - 375 mg (flat dose) Gemcitabine (Days 1 and 8) - 675 mg/m2 Docetaxel (Day 8) - 50 mg/m2
  • INCMGA00012
  • Gemcitabine
  • Docetaxel
Undifferentiated Pleomorphic Sarcoma/MyxofibrosarcomaExperimental(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 INCMGA00012) for cycle 1, with INCMGA00012 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 INCMGA00012 will continue until unacceptable toxicity, disease progression, or the completion of 35 cycles (105 weeks) of INCMGA00012 treatment.
  • INCMGA00012
  • Gemcitabine
  • Docetaxel
Liposarcoma/LPSExperimentalAfter 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 INCMGA00012) for cycle 1, with INCMGA00012 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 INCMGA00012 will continue until unacceptable toxicity, disease progression, or the completion of 35 cycles (105 weeks) of INCMGA00012 treatment.
  • INCMGA00012
  • Gemcitabine
  • Docetaxel
Leiomyosarcoma/LMSExperimentalAfter 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 INCMGA00012) for cycle 1, with INCMGA00012 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 INCMGA00012 will continue until unacceptable toxicity, disease progression, or the completion of 35 cycles (105 weeks) of INCMGA00012 treatment.
  • INCMGA00012
  • Gemcitabine
  • Docetaxel
Vascular SarcomaExperimentalAfter 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 INCMGA00012) for cycle 1, with INCMGA00012 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 INCMGA00012 will continue until unacceptable toxicity, disease progression, or the completion of 35 cycles (105 weeks) of INCMGA00012 treatment.
  • INCMGA00012
  • Gemcitabine
  • Docetaxel
Other Soft tissue sarcoma/STSExperimentalAfter 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 INCMGA00012) for cycle 1, with INCMGA00012 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 INCMGA00012 will continue until unacceptable toxicity, disease progression, or the completion of 35 cycles (105 weeks) of INCMGA00012 treatment.
  • INCMGA00012
  • Gemcitabine
  • Docetaxel

Eligibility Criteria

        Inclusion Criteria:

          -  Diagnosis of metastatic or locally advanced and unresectable high-grade soft tissue
             sarcoma. Unresectable is defined as:

               1. primary tumor cannot be safely removed surgically, or

               2. 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.

          -  No prior systemic therapy (see exclusion criteria, below)

          -  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:

        Table 2: Laboratory Parameters Required for Study Inclusion

        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

        Exclusion Criteria:

          -  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

          -  Current use of immunosuppressive medication, EXCEPT for the following:

               -  Intranasal, inhaled, topical steroids, or local steroid injection (e.g.,
                  intra-articular injection)

               -  Systemic corticosteroids at physiologic doses ≤ 10 mg/day of prednisone or
                  equivalent

               -  Steroids as premedication for hypersensitivity reactions (e.g., CT scan
                  premedication)

          -  Evidence of clinically significant immunosuppression such as the following:

               -  Primary immunodeficiency state such as Severe Combined Immunodeficiency Disease

               -  Concurrent opportunistic infection

               -  Receiving systemic immunosuppressive therapy (> 2 weeks) including oral steroid
                  doses > 10 mg/day of prednisone or equivalent within 2 months prior to enrollment

          -  History or evidence of symptomatic autoimmune disease in past 2 years prior to
             enrollment.

               -  Replacement therapy (e.g., thyroxine for hypothyroidism, insulin for diabetes or
                  physiologic corticosteroid replacement therapy for adrenal or pituitary
                  insufficiency) is not considered a form of systemic treatment for autoimmune
                  disease

          -  Uncontrolled HIV infection, as defined by one or more of the following:

               -  Patients with CD4+ T-cell (CD4+) counts < 350 cells/uL

               -  Patients with a history of an opportunistic infection secondary to AIDS

               -  Patients on anti-microbials with drug-drug interactions with the study drugs on
                  this protocol, who cannot be switched to alternative anti-microbials

               -  Patients on antiretroviral therapy < 4 weeks

               -  Patients with HIV viral load > 400 copies/mL

          -  Active Hepatitis B or Hepatitis C

          -  Patients who have received a live vaccine within 30 days of the start date of the
             planned study therapy

          -  History of active TB (Bacillus Tuberculosis)

          -  Radiation therapy within 2 weeks prior to study day 1

          -  If patient received major surgery, they must have recovered adequately from the
             toxicity and/or complications from the intervention prior to starting therapy

          -  Women who are pregnant or breast feeding

          -  Patients expecting to conceive or father children within the projected duration of the
             trial, starting with the pre-screening or screening visit through 120 days after the
             last dose of study treatment(s)

          -  Prior organ transplantation including allogenic stem-cell transplantation

          -  Active infection requiring systemic therapy

          -  Known prior severe hypersensitivity to investigational product or any component in its
             formulations, including known severe hypersensitivity reactions to monoclonal
             antibodies (NCI CTCAE v5.0 Grade ≥ 3)

          -  Patients with prior history of interstitial lung disease and clinically significant
             pulmonary compromise, including those who have a requirement for supplemental oxygen
             use to maintain adequate oxygenation
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Phase II: proportion of patients that are progression-free at 24 weeks by RECIST v1.1
Time Frame:24 weeks
Safety Issue:
Description: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.

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Memorial Sloan Kettering Cancer Center

Trial Keywords

  • soft tissue sarcoma
  • locally advanced soft tissue sarcoma
  • unresectable soft tissue sarcoma
  • metastasized soft tissue sarcoma
  • sarcoma
  • INCMGA00012
  • 20-316
  • Memorial Sloan Kettering Cancer Center

Last Updated

September 30, 2020