Clinical Trials /

Pembrolizumab and Monoclonal Antibody Therapy in Advanced Cancer

NCT02318901

Description:

There will be two phase II cohorts for pembro plus trastuzumab: one cohort will be for patients with unresectable HER2 overexpressing gastric or GEJ cancers, the other cohort will be for patients with HER2 overexpressing metastatic breast cancer (MBC). The pembro plus ado-trastuzumab emtansine phase II arm will be for patients with HER2 overexpressing MBC. There will be two phase II cohorts for pembro plus cetuximab: one cohort will be for patients with HNSCC, the other cohort will be for patients with K-ras, B-raf, N-ras wildtype metastatic CRC.

Related Conditions:
  • Adenocarcinoma of the Gastroesophageal Junction
  • Breast Carcinoma
  • Colorectal Carcinoma
  • Gastric Carcinoma
  • Head and Neck Squamous Cell Carcinoma
  • Malignant Solid Tumor
Recruiting Status:

Terminated

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Pembrolizumab and Monoclonal Antibody Therapy in Advanced Cancer
  • Official Title: A Phase Ib/II Study of Pembrolizumab and Monoclonal Antibody Therapy in Patients With Advanced Cancer (PembroMab

Clinical Trial IDs

  • ORG STUDY ID: PembroMab
  • NCT ID: NCT02318901

Conditions

  • Advanced Cancer
  • Breast Cancer
  • Gastric Cancer
  • Esophageal Cancer
  • Colorectal Cancer

Interventions

DrugSynonymsArms
PembrolizumabKEYTRUDAArm 1
TrastuzumabHerceptinArm 1
ado-trastuzumab emtansineKadcylaArm 2
CetuximabErbituxArm 3

Purpose

There will be two phase II cohorts for pembro plus trastuzumab: one cohort will be for patients with unresectable HER2 overexpressing gastric or GEJ cancers, the other cohort will be for patients with HER2 overexpressing metastatic breast cancer (MBC). The pembro plus ado-trastuzumab emtansine phase II arm will be for patients with HER2 overexpressing MBC. There will be two phase II cohorts for pembro plus cetuximab: one cohort will be for patients with HNSCC, the other cohort will be for patients with K-ras, B-raf, N-ras wildtype metastatic CRC.

Detailed Description

      Pembrolizumab 2mg/kg administered intravenously over 30 minutes every 3 weeks. Pembrolizumab
      will be infused prior to the start of the assigned monoclonal antibody (Mab) arm. .

      Dosing for the Mab arms will begin as follows:

      Arm 1: Cycle length is 21 days. Intravenous (i.v.) trastuzumab 6 mg/kg on day 1 every 21
      days.

      Arm 2: Cycle length is 21 days. i.v. ado-trastuzumab emtansine 3.6 mg/kg on day 1 every 21
      days.

      Arm 3: Cycle length is 21 days. i.v. cetuximab 400 mg/m2 on cycle 1 day 1, then i.v.
      cetuximab 250 mg/m2 on day 8. Each subsequent cycle will be i.v. cetuximab 250 mg/m2 on days
      1 and 8 every 21 days.
    

Trial Arms

NameTypeDescriptionInterventions
Arm 1ExperimentalPembrolizumab 2mg/kg administered intravenously over 30 minutes every 3 weeks. Intravenous (i.v.) trastuzumab 6 mg/kg on day 1 every 21 days.
  • Pembrolizumab
  • Trastuzumab
Arm 2ExperimentalPembrolizumab 2mg/kg administered intravenously over 30 minutes every 3 weeks. i.v. ado-trastuzumab emtansine 3.6 mg/kg on day 1 every 21 days.
  • Pembrolizumab
  • ado-trastuzumab emtansine
Arm 3ExperimentalPembrolizumab 2mg/kg administered intravenously over 30 minutes every 3 weeks. i.v. cetuximab 400 mg/m2 on cycle 1 day 1, then i.v. cetuximab 250 mg/m2 on day 8. Each subsequent cycle will be i.v. cetuximab 250 mg/m2 on days 1 and 8 every 21 days.
  • Pembrolizumab
  • Cetuximab

Eligibility Criteria

        Inclusion Criteria:

          1. Patient has definitive histologically or cytologically confirmed unresectable or
             metastatic solid tumor.

          2. Patient has one or more tumor measurable as defined by RECIST 1.1 by CT scan (or
             PET/CT, if patient is allergic to CT contrast media).

          3. Patients can be enrolled only on one of the treatment arms on this trial.

          4. The investigator will select the appropriate treatment arm for the patient with the
             following requirements: (a) Patients cannot have had prior progression or intolerance
             to a specific Mab and then enrolled on an arm with that same Mab plus pembro, (b) The
             Mab on the arm selected must be considered standard of care or listed in the NCCN
             guidelines (www.nccn.org) for that cancer type. For Arm 1, patients with HER2
             overexpressing MBC eligible for maintenance trastuzumab are allowed after taxane plus
             trastuzumab plus pertuzumab combination therapy.

          5. Have recovered from acute toxicities of prior treatment:

               1. > 3 weeks must have elapsed since receiving any investigational agent.

               2. > 2 weeks must have elapsed since receiving any radiotherapy, or ≥ 3 weeks or 5
                  half-lives whichever is shorter for treatment with cytotoxic or biologic agents (
                  ≥ 6 weeks for mitomycin or nitrosoureas). Chronic treatment with
                  non-investigational gonadotropin-releasing hormone analogs or other hormonal or
                  supportive care is permitted.

          6. Patient has adequate biological parameters as demonstrated by the following blood
             counts at time of screening:

          7. Absolute neutrophil count (ANC) > 1500 mm3, platelet count ≥ 100×109 L, hemoglobin ≥ 9
             g/dL.

          8. Serum creatinine ≤2.0, total bilirubin ≤ 2 mg/dL, AST/ALT ≤ 5 times the upper limit of
             normal (ULN) range

          9. Thyroid stimulating hormone (TSH) within institutional normal limits. If TSH is above
             the upper limit of normal range, then a free T4 within institutional normal limits is
             acceptable.

         10. Persistent prior systemic therapy non-hematologic AE grade ≥ 2 (except alopecia or
             correctable electrolyte abnormality with supplementation)

         11. Patient has a Karnofsky performance status (KPS) ≥ 70.

         12. Women of child-bearing potential (i.e., women who are pre-menopausal or not surgically
             sterile) must be willing to use an acceptable contraceptive method (abstinence, oral
             contraceptive or double barrier method) for the duration of the study and for 30 days
             following the last dose of study drug, and must have a negative urine or serum
             pregnancy test within 2 weeks prior to beginning treatment on this trial.

        Inclusion criteria for Phase II only:

          1. Patients must have unresectable HER2 overexpressing gastric or GEJ cancers to be
             enrolled on Cohort 1 of the pembro plus trastuzumab phase II portion.

          2. Patients must have HER2 overexpressing MBC to be enrolled on Cohort 2 of the pembro
             plus trastuzumab phase II portion.

          3. Patients must have HER2 overexpressing MBC to be enrolled on pembro plus
             ado-trastuzumab emtansine phase II portion.

          4. Patients must have HNSCC to be enrolled on Cohort 1 of the pembro plus cetuximab phase
             II portion.

          5. Patients must have K-ras, B-raf, N-ras wildtype CRC to be enrolled on Cohort 2 of the
             pembro plus cetuximab phase II portion.

        Exclusion Criteria:

          1. Active clinically serious infection > CTCAE (version 4.03) Grade 2.

          2. Serious non-healing wound, ulcer, or bone fracture.

          3. Patient has known brain metastases, unless previously treated and well-controlled for
             at least 1 month (defined as clinically stable, no edema, no steroids and stable in 2
             scans at least 4 weeks apart).

          4. Inability to complete informed consent process and adhere to the protocol treatment
             plan and follow-up requirements.

          5. Patient has known active infection with HIV, hepatitis B, or hepatitis C (patients are
             NOT required to be tested for the presence of such viruses prior to therapy on this
             protocol).

          6. Requiring daily corticosteroid dose ≥ 10 mg prednisone or equivalent per day.

          7. Patient has undergone major surgery, other than diagnostic surgery (e.g., surgery done
             to obtain a biopsy for diagnosis without removal of an organ), within 4 weeks prior to
             Day 1 of treatment in this study.

          8. Patient has a history of allergy or hypersensitivity to any of the study drugs or any
             of their excipients, or the patient exhibits any of the events outlined in the
             Contraindication or Special Warnings and Precautions sections of the product or
             comparator SmPC or Prescribing Information.

          9. Patient has serious medical risk factors involving any of the major organ systems, or
             serious psychiatric disorders, which could compromise the patient's safety or the
             study data integrity.

         10. Patient will be receiving any other anti-cancer therapy during participation in this
             trial.

         11. Prior treatment with pembro. Receipt of other PD-1 inhibitors or PD-L1 inhibitors is
             allowed.

         12. Active or prior documented autoimmune disease requiring systemic treatment within the
             past 2 years.

        Exclusion Criteria for phase II portion only:

        1. Patients with a history of more than one primary cancer, with the exception of: a)
        curatively resected nonmelanomatous skin cancer; b) curatively treated cervical carcinoma
        in-situ; or c) other primary solid tumor treated with curative intent and no known active
        disease present and no treatment administered during the 2 years prior to enrollment.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Determine the recommended phase 2 dose (RP2D) of monoclonal antibody therapy (Mab) in combination with pembrolizumab (pembro) in subjects with advanced cancer
Time Frame:3 weeks
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Frequency of grade 3 or higher treatment-related adverse events by CTCAE 4.03
Time Frame:up to 12 months
Safety Issue:
Description:
Measure:Response rate by irRC and response evaluation criteria in solid tumors (RECIST) 1.1 criteria
Time Frame:12 weeks
Safety Issue:
Description:
Measure:To determine the overall survival (OS) and progression-free survival (PFS)
Time Frame:up to 12 months
Safety Issue:
Description:
Measure:To characterize changes in circulating tumor DNA in patients enrolled on this study
Time Frame:up to 12 months
Safety Issue:
Description:
Measure:Textural changes identified on imaging that is done per routine practice
Time Frame:12 weeks
Safety Issue:
Description:

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Active, not recruiting
Lead Sponsor:Western Regional Medical Center

Last Updated

November 24, 2017