Don't get left behind! The modernized ClinicalTrials.gov is coming. Check it out now.
Say goodbye to ClinicalTrials.gov!
The new site is coming soon - go to the modernized ClinicalTrials.gov
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

A Study of Ladiratuzumab Vedotin in Advanced 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.
 
ClinicalTrials.gov Identifier: NCT04032704
Recruitment Status : Recruiting
First Posted : July 25, 2019
Last Update Posted : June 2, 2023
Sponsor:
Collaborator:
Merck Sharp & Dohme LLC
Information provided by (Responsible Party):
Seagen Inc.

Study Description
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
Brief Summary:
This trial will study ladiratuzumab vedotin (LV) alone and with pembrolizumab to find out if it works to treat different types of solid tumors. It will also find out what side effects may occur. A side effect is anything the drug does besides treating cancer.

Condition or disease Intervention/treatment Phase
Small Cell Lung Cancer Non-small Cell Lung Cancer, Squamous Non-small Cell Lung Cancer, Non-squamous Head and Neck Squamous Cell Carcinoma Esophageal Squamous Cell Carcinoma Gastric Adenocarcinoma Gastroesophageal Junction Adenocarcinoma Prostate Cancer Melanoma Drug: ladiratuzumab vedotin Drug: pembrolizumab Phase 2

Detailed Description:

This trial is designed to assess the antitumor activity, safety, and tolerability of LV alone and with pembrolizumab, for the treatment of solid tumors. Participants with the following advanced solid tumors will be enrolled:

Cohort 1: small cell lung cancer (SCLC) Cohort 2: non-small cell lung cancer-squamous (NSCLC-squamous) Cohort 3: non-small cell lung cancer-nonsquamous (NSCLC-nonsquamous) Cohort 4: head and neck squamous cell carcinoma (HNSCC) Cohort 5: esophageal squamous cell carcinoma (esophageal-squamous) Cohort 6: gastric and gastroesophageal junction (GEJ) adenocarcinoma Cohort 7: castration-resistant prostate cancer (CRPC) Cohort 8: melanoma

Participants will continue to receive study treatment until disease progression, unacceptable toxicity, investigator decision, consent withdrawal, study termination by the sponsor, pregnancy, or death, whichever comes first.

Study Design
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 414 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Open-Label Phase 2 Study of Ladiratuzumab Vedotin (LV) for Unresectable Locally Advanced or Metastatic Solid Tumors
Actual Study Start Date : October 9, 2019
Estimated Primary Completion Date : May 31, 2024
Estimated Study Completion Date : July 31, 2025

Resource links provided by the National Library of Medicine


Arms and Interventions
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Arm Intervention/treatment
Experimental: Part A: Non-randomized LV monotherapy
Monotherapy dosing schedule 1.
 Drug: ladiratuzumab vedotin
Intravenous (into the vein; IV) infusion
Other Name: SGN-LIV1A
Experimental: Part B: Non-randomized LV monotherapy
Monotherapy dosing schedule 2.
 Drug: ladiratuzumab vedotin
Intravenous (into the vein; IV) infusion
Other Name: SGN-LIV1A
Experimental: Part C - Arm 1: Randomized LV monotherapy
Monotherapy dosing schedule 3.
 Drug: ladiratuzumab vedotin
Intravenous (into the vein; IV) infusion
Other Name: SGN-LIV1A
Experimental: Part C - Arm 2: Randomized LV combination therapy
Combination dosing schedule 1.
 Drug: ladiratuzumab vedotin
Intravenous (into the vein; IV) infusion
Other Name: SGN-LIV1A

Drug: pembrolizumab
200mg given by IV on Day 1 of each 21-day cycle
Other Name: Keytruda
Experimental: Part C - Arm 3: Randomized LV combination therapy
Combination dosing schedule 2.
 Drug: ladiratuzumab vedotin
Intravenous (into the vein; IV) infusion
Other Name: SGN-LIV1A

Drug: pembrolizumab
200mg given by IV on Day 1 of each 21-day cycle
Other Name: Keytruda


Outcome Measures
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Primary Outcome Measures :
  1. Confirmed objective response rate (ORR) as determined by investigator according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) [ Time Frame: Up to approximately 1 year ]
    Confirmed ORR is defined as the proportion of participants who achieve a confirmed complete response (CR) or partial response (PR) according to RECIST v1.1 as assessed by the investigator.

  2. Prostate-specific antigen (PSA) response rate as determined by investigator according to Prostate Cancer Clinical Trials Working Group 3 (PCWG3) criteria (Cohort 7 only) [ Time Frame: Up to approximately 1 year ]
    Confirmed PSA response rate is defined as the proportion of participants with a reduction from baseline PSA level of at least 50%, measured twice ≥3 weeks apart.


Secondary Outcome Measures :
  1. Number of participants with adverse events (AEs) [ Time Frame: Up to approximately 1 year ]
    An AE is any untoward medical occurrence in a clinical investigational participant administered a medicinal product and which does not necessarily have a causal relationship with this treatment.

  2. Disease control rate (DCR) as determined by investigator according to RECIST v1.1 [ Time Frame: Up to approximately 1 year ]
    DCR is defined as the proportion of participants who achieve a confirmed CR or PR according to RECIST v1.1 as assessed by the investigator, or meet the stable disease (SD) criteria at least once after start of study treatment at a minimum interval of 5 weeks or 7 weeks for prostate cancer subjects.

  3. Duration of response (DOR) as determined by investigator according to RECIST v1.1 [ Time Frame: Up to approximately 1 year ]
    DOR is defined as the time from the first documentation of objective response (CR or PR that is subsequently confirmed) to the first documentation of progressive disease (PD) or death due to any cause, whichever comes first.

  4. PSA-DOR as determined by investigator assessment (Cohort 7 only) [ Time Frame: Up to approximately 1 year ]
    PSA-DOR is defined as the time from the first documentation of PSA response to the first documentation of PSA progression or death, whichever comes first

  5. Progression-free survival (PFS) as determined by investigator according to RECIST v1.1 [ Time Frame: Up to approximately 1 year ]
    PFS is defined as the time from the start of study treatment to the first documentation of PD by RECIST v1.1 or clinical PD or by PSA progression (prostate cancer cohort) or death due to any cause, whichever comes first.

  6. PSA-PFS as determined by investigator assessment (Cohort 7 only) [ Time Frame: Up to approximately 1 year ]
    PSA-PFS is defined as the time from the start of study treatment to first occurrence of PSA progression or death, whichever comes first

  7. Overall survival (OS) [ Time Frame: Up to approximately 1 year ]
    OS is defined as the time from the start of study treatment to date of death due to any cause.

  8. Maximum observed concentration (Cmax) [ Time Frame: Up to approximately 1 year ]
    Pharmacokinetic (PK) endpoint of LV

  9. Area under the concentration-time curve (AUC) [ Time Frame: Up to approximately 1 year ]
    PK endpoint of LV

  10. Incidence of antitherapeutic antibodies (ATAs) to LV [ Time Frame: Up to approximately 1 year ]

Eligibility Criteria
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

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.


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

Inclusion Criteria

  • All Cohorts

    • Measurable disease according to RECIST v1.1 as assessed by the investigator
    • Eastern Cooperative Oncology Group (ECOG) Performance Score of 0 or 1

  • Cohort 1: SCLC (Parts A and B)

    • Must have extensive stage disease
    • Must have disease progression during or following prior platinum-based systemic chemotherapy for extensive stage disease;
    • No more than 1 prior line of cytotoxic chemotherapy for extensive disease stage
    • May have received prior anti-PD(L)1 therapy

  • Cohort 2: NSCLC-squamous (Parts A and B)

    • Must have unresectable locally advanced or metastatic disease

    • Must have disease progression during or following systemic therapy

      • Participants must have progressed during or after a platinum-based combination therapy administered for the treatment of metastatic disease, OR
      • Participants must have progressed within 6 months of last dose of platinum-based adjuvant, neoadjuvant, or definitive chemotherapy, or concomitant chemoradiation regimen for early stage or locally advanced stage disease.
    • Participants with known epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), reactive oxygen species (ROS), BRAF, or other actionable mutations are not eligible
    • No more than 1 prior line of cytotoxic chemotherapy for their advanced disease
    • Must have received prior anti-PD(L)1 therapy, unless contraindicated

  • Cohort 3: NSCLC-nonsquamous (Parts A and B)

    • Must have unresectable locally advanced or metastatic disease

    • Must have disease progression during or following systemic therapy

      • Participants must have progressed during or after a platinum-based combination therapy administered for the treatment of metastatic disease, OR
      • Participants must have progressed within 6 months of last dose of platinum-based adjuvant, neoadjuvant, or definitive chemotherapy, or concomitant chemoradiation regimen for early stage or locally advanced state disease.
    • Participants with known EGFR, ALK, ROS, BRAF, tropomyosin receptor kinase (TRK), or other actionable mutations are not eligible
    • Must have had prior platinum-based chemotherapy
    • No more than 1 prior line of cytotoxic chemotherapy for their advanced disease
    • Must have received prior anti-PD(L)1 therapy, unless contraindicated

  • Cohort 4: HNSCC (Parts A and B)

    • Must have unresectable locally recurrent or metastatic disease

      • Must have disease progression during or following prior line of systemic therapy
      • Disease progression after treatment with a platinum-containing regimen for recurrent/metastatic disease; OR
      • Recurrence/progression within 6 months of last dose of platinum therapy given as part of a multimodal therapy in the curative setting
    • No more than 1 line of cytotoxic chemotherapy for their advanced disease
    • May have received prior anti-PD(L)1 therapy, unless contraindicated

  • Cohort 5: esophageal-squamous (Parts A and B)

    • Must have unresectable locally advanced or metastatic disease
    • Must have disease progression during or following systemic therapy
    • Must have had prior platinum-based chemotherapy
    • No more than 1 line of cytotoxic chemotherapy for their advanced disease

  • Cohort 6: gastric and GEJ adenocarcinoma (Parts A and B)

    • Must have unresectable locally advanced or metastatic disease
    • Must have received prior platinum-based therapy
    • Must have disease progression during or following systemic therapy
    • Participants with known human epidermal growth factor receptor 2 (HER2) overexpression must have received prior HER2-targeted therapy
    • No more than 1 line of prior cytotoxic chemotherapy for their advanced disease
    • Participants may have received prior anti-PD(L)1 therapy, unless contraindicated

  • Cohort 7: CRPC (Part B only)

    • Must have histologically or cytologically confirmed adenocarcinoma of the prostate

      • Participants with components of small cell of neuroendocrine histology are excluded
    • Must have metastatic castration-resistant disease
    • Must have been ≥28 days between cessation of androgen receptor-targeted therapy and start of study treatment
    • Must have received no more than 1 prior line of androgen receptor-targeted therapy for metastatic castration-sensitive prostate cancer or CRPC

    • No prior cytotoxic chemotherapy in the metastatic CRPC setting

      • For participants who received cytotoxic chemotherapy in CSPC, at least 6 months must have elapsed between last dose of chemotherapy and start of study treatment
      • No more than 1 prior line of cytotoxic chemotherapy for CSPC

    • Participants with measurable disease are eligible if the following criteria are met:

      • A minimum starting PSA level ≥1.0 ng/mL
      • Participants with measurable soft tissue disease must have evidence of measurable soft tissue disease according to PCWG3 criteria.
    • Participants with known breast cancer gene (BRCA) mutations are excluded
    • No prior radioisotope therapy or radiotherapy to ≥30% of bone marrow

  • Cohort 8: Melanoma (Parts B and C)

    • Must have histologically or cytologically confirmed cutaneous malignant melanoma

      • Participants with mucosal, acral, or uveal melanoma are excluded
    • Must have locally advanced unresectable or metastatic stage disease
    • Must have progressive disease following anti-PD(L)1 therapy
    • Must have received BRAF +/- MEK inhibitor therapy if BRAF mutated (Part C)

Exclusion Criteria

  • Active concurrent malignancy or a previous malignancy within the past 3 years
  • Any anticancer therapy within 3 weeks of starting study treatment. Participants who are/were on adjuvant hormonal therapy for the treatment of malignancies with negligible risk of metastases are eligible.
  • Known active central nervous system lesions
  • Any ongoing clinically significant toxicity associated with prior treatment (Grade 2 or higher)
  • Ongoing sensory or motor neuropathy of Grade ≥2
  • Has received prior radiotherapy within 2 weeks of start of study treatment
  • History of interstitial lung disease.
Contacts and Locations
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

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 ClinicalTrials.gov identifier (NCT number): NCT04032704


Contacts
Layout table for location contacts
Contact: Seagen Trial Information Support 866-333-7436 clinicaltrials@seagen.com

Locations
Show Show 66 study locations
Sponsors and Collaborators
Seagen Inc.
Merck Sharp & Dohme LLC
Investigators
Layout table for investigator information
Study Director: Brandon Croft, PharmD Seagen Inc.
More Information
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
Layout table for additonal information
Responsible Party: Seagen Inc.
ClinicalTrials.gov Identifier: NCT04032704    
Other Study ID Numbers: SGNLVA-005
First Posted: July 25, 2019    Key Record Dates
Last Update Posted: June 2, 2023
Last Verified: May 2023

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Seagen Inc.:
SCLC
NSCLC-squamous
NSCLC-nonsquamous
 HNSCC
GEJ adenocarcinoma
Seattle Genetics
Additional relevant MeSH terms:
Layout table for MeSH terms
Carcinoma
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Carcinoma, Squamous Cell
Adenocarcinoma
Small Cell Lung Carcinoma
Squamous Cell Carcinoma of Head and Neck
Esophageal Squamous Cell Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Lung Diseases
 Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Neoplasms, Squamous Cell
Head and Neck Neoplasms
Esophageal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Digestive System Diseases
Esophageal Diseases
Gastrointestinal Diseases
Pembrolizumab
SGN-LIV1A
Antineoplastic Agents, Immunological
Antineoplastic Agents