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Brentuximab Vedotin With Pembrolizumab in Metastatic Solid Tumors

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT04609566
Recruitment Status : Recruiting
First Posted : October 30, 2020
Last Update Posted : April 13, 2021
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
Seagen Inc.

Brief Summary:

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.

Condition or disease Intervention/treatment Phase
Melanoma Non-small Cell Lung Cancer Drug: brentuximab vedotin Drug: pembrolizumab Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 60 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : January 26, 2021
Estimated Primary Completion Date : March 31, 2022
Estimated Study Completion Date : September 30, 2023

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: Combination Therapy
brentuximab vedotin + pembrolizumab
Drug: brentuximab vedotin
1.8 mg/kg given intravenously (IV; into the vein) every 3 weeks
Other Name: ADCETRIS

Drug: pembrolizumab
200 mg given intravenously every 3 weeks
Other Name: KEYTRUDA

Primary Outcome Measures :
  1. Confirmed objective response rate (ORR) based on investigator assessment using RECIST 1.1 criteria [ Time Frame: Up to approximately 2 years ]
    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 :
  1. Duration of response (DOR) based on investigator assessment using RECIST 1.1 criteria [ Time Frame: Up to approximately 3 years ]
    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.

  2. Progression-free survival (PFS) based on investigator assessment using RECIST 1.1 criteria [ Time Frame: Up to approximately 3 years ]
    PFS is defined as the time from start of study treatment to first documentation of objective tumor progression (PD per RECIST 1.1)

  3. ORR per iRECIST by investigator assessment [ Time Frame: Up to approximately 2 years ]
    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

  4. DOR per iRECIST by investigator assessment [ Time Frame: Up to approximately 3 years ]
    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.

  5. Incidence of adverse events (AEs) [ Time Frame: Up to approximately 2 years ]
    National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0. Analyses of AEs will be summarized with descriptive statistics.

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT04609566

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Contact: Seagen Trial Information Support 866-333-7436

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Sponsors and Collaborators
Seagen Inc.
Merck Sharp & Dohme Corp.
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Study Director: Scott Knowles, MD, PhD Seagen Inc.
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Responsible Party: Seagen Inc. Identifier: NCT04609566    
Other Study ID Numbers: SGN35-033
KEYNOTE B81 ( Other Identifier: Merck & Co )
First Posted: October 30, 2020    Key Record Dates
Last Update Posted: April 13, 2021
Last Verified: April 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Seagen Inc.:
Seattle Genetics
Additional relevant MeSH terms:
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Carcinoma, Non-Small-Cell Lung
Carcinoma, Bronchogenic
Bronchial Neoplasms
Lung Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Lung Diseases
Respiratory Tract Diseases
Antineoplastic Agents, Immunological
Antineoplastic Agents