A Study of Ladiratuzumab Vedotin in Advanced Solid Tumors

• ClinicalTrials.gov Identifier: NCT04032704
• Recruitment Status: Recruiting
• First Posted: July 25, 2019
• Last Update Posted: March 7, 2023
• Sponsor: Seagen Inc.
• Collaborator: Merck Sharp & Dohme LLC
• Information provided by (Responsible Party): Seagen Inc.

Tracking Information

• First Submitted Date: July 23, 2019
• First Posted Date: July 25, 2019
• Last Update Posted Date: March 7, 2023
• Actual Study Start Date: October 9, 2019
• Estimated Primary Completion Date: May 31, 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: December 19, 2022)

• 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.
• 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.

• Original Primary Outcome Measures (submitted: July 23, 2019): Confirmed objective response rate (ORR) as determined by investigator according to RECIST v1.1 [ Time Frame: Up to approximately 1 year ]

Current Secondary Outcome Measures (submitted: December 19, 2022)

• 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.
• 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.
• 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.
• 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
• 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.
• 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
• 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.
• Maximum observed concentration (Cmax) [ Time Frame: Up to approximately 1 year ]
  Pharmacokinetic (PK) endpoint of LV
• Area under the concentration-time curve (AUC) [ Time Frame: Up to approximately 1 year ]
  PK endpoint of LV
• Incidence of antitherapeutic antibodies (ATAs) to LV [ Time Frame: Up to approximately 1 year ]

Original Secondary Outcome Measures (submitted: July 23, 2019)

• Number of participants with adverse events (AEs) [ Time Frame: Up to approximately 1 year ]
• Disease control rate (DCR) as determined by investigator according to RECIST v1.1 [ Time Frame: Up to approximately 1 year ]
• Duration of response (DOR) as determined by investigator according to RECIST v1.1 [ Time Frame: Up to approximately 1 year ]
• Progression-free survival (PFS) as determined by investigator according to RECIST v1.1 [ Time Frame: Up to approximately 1 year ]
• Overall survival (OS) [ Time Frame: Up to approximately 1 year ]
• Maximum observed concentration (Cmax) [ Time Frame: Up to approximately 1 year ]
  Pharmacokinetic (PK) endpoint of LV
• Area under the concentration-time curve (AUC) [ Time Frame: Up to approximately 1 year ]
  PK endpoint of LV
• Incidence of antitherapeutic antibodies (ATAs) to LV [ Time Frame: Up to approximately 1 year ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• 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
• 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.

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 Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• 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

Intervention

• 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

Study Arms

• Experimental: Part A: Non-randomized LV monotherapy
  Monotherapy dosing schedule 1.
  Intervention: Drug: ladiratuzumab vedotin
• Experimental: Part B: Non-randomized LV monotherapy
  Monotherapy dosing schedule 2.
  Intervention: Drug: ladiratuzumab vedotin
• Experimental: Part C - Arm 1: Randomized LV monotherapy
  Monotherapy dosing schedule 3.
  Intervention: Drug: ladiratuzumab vedotin
• Experimental: Part C - Arm 2: Randomized LV combination therapy
  Combination dosing schedule 1.
  Interventions:

  • Drug: ladiratuzumab vedotin
  • Drug: pembrolizumab
• Experimental: Part C - Arm 3: Randomized LV combination therapy
  Combination dosing schedule 2.
  Interventions:

  • Drug: ladiratuzumab vedotin
  • Drug: pembrolizumab

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: December 19, 2022): 414
• Original Estimated Enrollment (submitted: July 23, 2019): 180
• Estimated Study Completion Date: July 31, 2025
• Estimated Primary Completion Date: May 31, 2024 (Final data collection date for primary outcome measure)

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 (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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Seagen Trial Information Support; 866-333-7436; clinicaltrials@seagen.com

• Listed Location Countries: Australia, Italy, Korea, Republic of, Taiwan, United Kingdom, United States

Administrative Information

• NCT Number: NCT04032704
• Other Study ID Numbers: SGNLVA-005
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Seagen Inc.
• Original Responsible Party: Same as current
• Current Study Sponsor: Seagen Inc.
• Original Study Sponsor: Same as current
• Collaborators: Merck Sharp & Dohme LLC

Investigators

• Study Director: Brandon Croft, PharmD; Seagen Inc.

• PRS Account: Seagen Inc.
• Verification Date: March 2023