Clinical Trials /

Brentuximab Vedotin With Pembrolizumab in Metastatic Solid Tumors

NCT04609566

Description:

This trial will find out whether brentuximab vedotin and pembrolizumab work together to treat different types of cancer. There will be several different types of cancer studied in the trial. The cancer must have spread to other parts of the body (metastatic) and must have gotten worse (progressed) after being treated with a PD-1 inhibitor treatment. The study will also find out what side effects occur. A side effect is anything the treatment does besides treat cancer. This is a multi-cohort study.

Related Conditions:
  • Cutaneous Melanoma
  • Non-Small Cell Lung Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Brentuximab Vedotin With Pembrolizumab in Metastatic Solid Tumors
  • Official Title: A Phase 2 Study of Brentuximab Vedotin in Combination With Pembrolizumab in Subjects With Metastatic Solid Malignancies After Progression on Prior PD-1 Inhibitor Treatment

Clinical Trial IDs

  • ORG STUDY ID: SGN35-033
  • SECONDARY ID: KEYNOTE B81
  • NCT ID: NCT04609566

Conditions

  • Melanoma
  • Non-small Cell Lung Cancer

Interventions

DrugSynonymsArms
brentuximab vedotinADCETRISCombination Therapy
pembrolizumabKEYTRUDACombination Therapy

Purpose

This trial will find out whether brentuximab vedotin and pembrolizumab work together to treat different types of cancer. There will be several different types of cancer studied in the trial. The cancer must have spread to other parts of the body (metastatic) and must have gotten worse (progressed) after being treated with a PD-1 inhibitor treatment. The study will also find out what side effects occur. A side effect is anything the treatment does besides treat cancer. This is a multi-cohort study.

Trial Arms

NameTypeDescriptionInterventions
Combination TherapyExperimentalbrentuximab vedotin + pembrolizumab
  • brentuximab vedotin
  • pembrolizumab

Eligibility Criteria

        Inclusion Criteria

          -  Must have relapsed or refractory metastatic squamous or nonsquamous non-small cell
             lung cancer (NSCLC; EGFR, ALK, ROS1, and BRAF negative) or metastatic cutaneous
             melanoma (including participants without targetable gene mutations and
             BRAF-V600E/V600K participants who have failed targeted therapy)

          -  Participants must be currently on PD-1 checkpoint inhibitor therapy (nivolumab or
             pembrolizumab) or have been on a PD-1 checkpoint inhibitor containing therapy as the
             last previous line of therapy within 90 days prior to enrollment; PD-1 checkpoint
             inhibitor therapy should be the immediate prior line of treatment.

          -  Participants must have progressed on treatment with an anti-PD1 monoclonal antibody
             (mAb) administered either as monotherapy, or in combination with other checkpoint
             inhibitors or other therapies. PD-1 treatment progression is defined by meeting all of
             the following criteria.

               -  Participants with refractory disease must have progressed without a prior
                  objective response during or after prior PD-1 inhibitor therapy within 3 months
                  OR

               -  Participants with relapsed diseased must have progressed after having developed a
                  prior objective response of CR/PR for at least 3 months or SD for at least 6
                  months AND

               -  Have received at least 2 doses of an approved anti-PD-1 mAb.

               -  Have demonstrated disease progression (PD) after PD-1 as defined by RECIST v1.1.
                  The initial evidence of PD is to be confirmed by a second assessment no less than
                  four weeks from the date of the first documented PD, in the absence of rapid
                  clinical progression.

                    -  Progressive disease has been documented within 12 weeks from the last dose
                       of anti-PD-1 mAb.

                    -  Progressive disease is determined according to iRECIST.

                    -  This determination is made by the investigator. Once PD is confirmed, the
                       initial date of PD documentation will be considered the date of disease .

          -  Tumor tissue sample obtained within 3 months prior to enrollment is required, and no
             systemic anticancer therapy given after the sample was obtained.

          -  An Eastern Cooperative Oncology Group (ECOG) Performance Status score of equal or less
             than 1

        Exclusion Criteria

          -  Has known active CNS metastases and/or carcinomatous meningitis.

          -  Prior immunosuppressive chemotherapy, therapeutic radiation, or any immunotherapy
             within 4 weeks of first study drug dose.

          -  History of another malignancy within 3 years before the first dose of study drug or
             any evidence of residual disease from a previously diagnosed malignancy.

          -  History of progressive multifocal leukoencephalopathy (PML).

          -  Any uncontrolled Grade 3 or higher (per the National Cancer Institute's Common
             Terminology Criteria for Adverse Events, NCI CTCAE Version 5.0) viral, bacterial, or
             fungal infection within 2 weeks prior to the first dose of study drug. Routine
             antimicrobial prophylaxis is permitted.

          -  Participants who are breastfeeding.

          -  Known to be positive for hepatitis B by surface antigen expression. Known to be
             positive for hepatitis C infection. Participants who have been treated for hepatitis C
             infection are permitted if they have documented sustained virologic response of 12
             weeks.

          -  Previous treatment with brentuximab vedotin

          -  Grade 3 or higher pulmonary disease unrelated to underlying malignancy

          -  Documented history of a cerebral vascular event, unstable angina, myocardial
             infarction, or cardiac symptoms consistent with New York Heart Association Class
             III-IV within 6 months prior to their first dose of brentuximab vedotin

          -  Congestive heart failure, Class III or IV, by the New York Heart Association criteria

          -  Grade 2 or higher peripheral sensory or motor neuropathy at baseline

          -  Idiopathic interstitial pneumonia or diffusing capacity of the lung for carbon
             monoxide (DLCO; adjusted for hemoglobin) <50% predicted.

          -  Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy
             (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of
             immunosuppressive therapy within 7 days prior the first dose of study drug.

          -  Has an active autoimmune disease that has required systemic treatment in past 2 years.
             Replacement therapy is not considered a form of systemic treatment and is allowed.

          -  HIV-infected participants with a history of Kaposi sarcoma and/or Multicentric
             Castleman Disease.

          -  Has received prior radiotherapy within 2 weeks of start of study treatment.
             Participants must have recovered from all radiation-related toxicities, not require
             corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted
             for palliative radiation (≤2 weeks of radiotherapy) to non-CNS disease.

          -  Has a history of (non-infectious) pneumonitis that required steroids or has current
             pneumonitis.

          -  For NSCLC participants: Has received radiation therapy to the lung that is >30 Gy
             within 6 months of the first dose of trial treatment

          -  Has had an allogenic tissue/solid organ transplant.

          -  Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti PD L2 agent or with
             an agent directed to another stimulatory or co-inhibitory T-cell receptor and was
             discontinued from that treatment due to a Grade 3 or higher irAE.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Confirmed objective response rate (ORR) based on investigator assessment using RECIST 1.1 criteria
Time Frame:Up to approximately 2 years
Safety Issue:
Description:Confirmed ORR per RECIST 1.1 is defined as the proportion of participants whose best overall response is a confirmed complete response (CR) or partial response (PR) per RECIST 1.1.

Secondary Outcome Measures

Measure:Duration of response (DOR) based on investigator assessment using RECIST 1.1 criteria
Time Frame:Up to approximately 3 years
Safety Issue:
Description:DOR per RECIST 1.1 is defined as the time from start of the first documentation of confirmed objective tumor response (CR or PR) per RECIST 1.1 to the first documentation of PD (per RECIST v1.1) or to death due to any cause, whichever comes first.
Measure:Progression-free survival (PFS) based on investigator assessment using RECIST 1.1 criteria
Time Frame:Up to approximately 3 years
Safety Issue:
Description:PFS is defined as the time from start of study treatment to first documentation of objective tumor progression (PD per RECIST 1.1)
Measure:ORR per iRECIST by investigator assessment
Time Frame:Up to approximately 2 years
Safety Issue:
Description:ORR per RECIST 1.1 is defined as the proportion of participants whose best overall response is confirmed CR or PR based on iRECIST guidelines
Measure:DOR per iRECIST by investigator assessment
Time Frame:Up to approximately 3 years
Safety Issue:
Description:DOR per iRECIST is defined as the time from first documentation of confirmed objective response (CR or PR) based on iRECIST guidelines by investigator assessment to the first documentation of confirmed objective tumor progression per iRECIST by investigator assessment, or to death due to any casuse, whichever comes first.
Measure:Incidence of adverse events (AEs)
Time Frame:Up to approximately 2 years
Safety Issue:
Description:National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0. Analyses of AEs will be summarized with descriptive statistics.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Seagen Inc.

Trial Keywords

  • Seattle Genetics

Last Updated

November 10, 2020