Clinical Trials /

A Study of Ladiratuzumab Vedotin in Advanced Solid Tumors

NCT04032704

Description:

This trial will study ladiratuzumab vedotin (LV) 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.

Related Conditions:
  • Adenocarcinoma of the Gastroesophageal Junction
  • Cutaneous Melanoma
  • Esophageal Squamous Cell Carcinoma
  • Gastric Adenocarcinoma
  • Head and Neck Squamous Cell Carcinoma
  • Non-Squamous Non-Small Cell Lung Carcinoma
  • Prostate Adenocarcinoma
  • Small Cell Lung Carcinoma
  • Squamous Cell Lung Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: A Study of Ladiratuzumab Vedotin in Advanced Solid Tumors
  • Official Title: Open-Label Phase 2 Study of Ladiratuzumab Vedotin (LV) for Unresectable Locally Advanced or Metastatic Solid Tumors

Clinical Trial IDs

  • ORG STUDY ID: SGNLVA-005
  • NCT ID: NCT04032704

Conditions

  • 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

Interventions

DrugSynonymsArms
ladiratuzumab vedotinSGN-LIV1ALadiratuzumab Vedotin

Purpose

This trial will study ladiratuzumab vedotin (LV) 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.

Detailed Description

      This trial is designed to assess the antitumor activity, safety, and tolerability of LV 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.
    

Trial Arms

NameTypeDescriptionInterventions
Ladiratuzumab VedotinExperimentalSGN-LIV1A monotherapy
  • ladiratuzumab vedotin

Eligibility 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

               -  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

               -  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

               -  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

               -  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

               -  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

               -  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

               -  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

               -  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 and non-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 non-measurable disease must have documented rising PSA
                       levels or appearance of new lesion according to PCWG3

               -  Participants with known breast cancer gene (BRCA) mutations are excluded

               -  No prior radioscope therapy or radiotherapy to ≥30% of bone marrow

          -  Cohort 8: Melanoma

               -  Must have histologically or cytotoxically confirmed cutaneous malignant melanoma

                    -  Participants with mucosal, acral, or uveal melanoma are excluded

               -  Must have locally advanced unresectable or metastatic stage disease

               -  Must have measurable disease

               -  Must have progressive disease following anti-PD(L)1 therapy

        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

          -  Active viral, bacterial, or fungal infection requiring systemic treatment within 7
             days prior to the first dose of LV

          -  Any ongoing clinically significant toxicity associated with prior treatment (Grade 2
             or higher)

          -  Ongoing sensory or motor neuropathy of Grade ≥2

          -  Documented history of a cerebral vascular event (stroke or transient ischemic attack),
             unstable angina, myocardial infarction, or cardiac symptoms consistent with congestive
             heart failure

          -  Has received prior radiotherapy within 2 weeks of start of study treatment

          -  Has received a live vaccine within 30 days of the planned start of study therapy.
      
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) as determined by investigator according to RECIST v1.1
Time Frame:Up to approximately 1 year
Safety Issue:
Description: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.

Secondary Outcome Measures

Measure:Number of participants with adverse events (AEs)
Time Frame:Up to approximately 1 year
Safety Issue:
Description:
Measure:Disease control rate (DCR) as determined by investigator according to RECIST v1.1
Time Frame:Up to approximately 1 year
Safety Issue:
Description:DCR is defined as the proportion of participants who achieve a confirmed CR or PR, or meet the stable disease (SD) criteria at least once after start of study treatment at a minimum interval of 5 weeks.
Measure:Duration of response (DOR) as determined by investigator according to RECIST v1.1
Time Frame:Up to approximately 1 year
Safety Issue:
Description: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.
Measure:PSA-DOR as determined by investigator assessment (Cohort 7 only)
Time Frame:Up to approximately 1 year
Safety Issue:
Description: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
Measure:Progression-free survival (PFS) as determined by investigator according to RECIST v1.1
Time Frame:Up to approximately 1 year
Safety Issue:
Description:Progression-free survival (PFS) is defined as the time from the start of study treatment to the first documentation of PD or death due to any cause, whichever comes first.
Measure:PSA-PFS as determined by investigator assessment (Cohort 7 only)
Time Frame:Up to approximately 1 year
Safety Issue:
Description:PSA-PFS is defined as the time from the start of study treatment to first occurrence of PSA progression or death, whichever comes first
Measure:Overall survival (OS)
Time Frame:Up to approximately 1 year
Safety Issue:
Description:OS is defined as the time from the start of study treatment to date of death due to any cause.
Measure:Maximum observed concentration (Cmax)
Time Frame:Up to approximately 1 year
Safety Issue:
Description:Pharmacokinetic (PK) endpoint of LV
Measure:Area under the concentration-time curve (AUC)
Time Frame:Up to approximately 1 year
Safety Issue:
Description:PK endpoint of LV
Measure:Incidence of antitherapeutic antibodies (ATAs) to LV
Time Frame:Up to approximately 1 year
Safety Issue:
Description:

Details

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

Trial Keywords

  • SCLC
  • NSCLC-squamous
  • NSCLC-nonsquamous
  • HNSCC
  • GEJ adenocarcinoma
  • Seattle Genetics

Last Updated

February 2, 2021