Clinical trial NCT04032704: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
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
Keywords: SCLC
NSCLC-squamous
NSCLC-nonsquamous
HNSCC
GEJ adenocarcinoma
Seattle Genetics
Lead sponsor: Seagen Inc.
Sponsor class: INDUSTRY
Collaborators: name: Merck Sharp & Dohme LLC
First posted: 2019-07-25
Enrollment: 205
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Part A: Confirmed Objective Response Rate (ORR) as Determined by Investigator According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)
timeFrame: From the first dose of study treatment until the first documented CR or PR or new anticancer therapies or death, whichever occurred first (maximum up to 8.3 months)
measure: Part B: Confirmed ORR as Determined by Investigator According to RECIST v1.1
timeFrame: From the first dose of study treatment until the first documented CR or PR or new anticancer therapies or death, whichever occurred first (maximum up to 34.7 months for 1.25 mg/kg and 5.7 months for 1 mg/kg dose level)
measure: Part B: Confirmed Prostate-Specific Antigen (PSA) Response Rate as Determined by Investigator According to Prostate Cancer Clinical Trials Working Group 3 (PCWG3) Criteria, for Prostate Cancer
timeFrame: From the first dose of study treatment up to the date of last response assessment (maximum up to 13.5 months)
Secondary outcomes:
measure: Part A: Number of Participants With Treatment Emergent Adverse Events (TEAEs), Treatment Emergent Serious Adverse Events (TESAEs), Treatment Related TEAEs and >= Grade 3 TEAE
timeFrame: From start of study treatment up to 30 days after last dose of study treatment (maximum up to 37.5 months)
measure: Part B: Number of Participants With TEAEs, TESAEs, Treatment Related TEAEs and >= Grade 3 TEAE
timeFrame: From start of study treatment up to 30 days after last dose of study treatment (maximum up to 37.5 months)
measure: Part A: Confirmed Investigator Determined Disease Control Rate (DCR) According to RECIST v1.1
timeFrame: From the first dose of study treatment until the first documented CR, PR or SD or new anticancer therapies or death, whichever occurred first (maximum up to 4.1 months)
measure: Part B: Confirmed Investigator Determined DCR According to RECIST v1.1
timeFrame: From the first dose of study treatment until the first documented CR, PR or SD or new anticancer therapies or death, whichever occurred first (maximum up to 5.5 months for 1.25 mg/kg and 1.5 months for 1 mg/kg dose level)
measure: Part A: Confirmed Investigator Determined Duration of Response (DOR) According to RECIST v1.1
timeFrame: From the first documentation of CR or PR to PD or death or censoring whichever occurred first (maximum up to 5.7 months)
measure: Part B: Confirmed Investigator Determined DOR According to RECIST v1.1
timeFrame: From the first documentation of CR or PR to PD or death or censoring whichever occurred first (maximum up to 32.0 months for 1.25 mg/kg and 4.2 months for 1 mg/kg dose level)
measure: Part B: Confirmed Investigator Determined PSA-DOR, for Prostate Cancer
timeFrame: From the first documentation of CR or PR to PD or death or censoring whichever occurred first (maximum up to 3 months)
measure: Part A: Confirmed Investigator Determined Progression Free Survival (PFS) According to RECIST v1.1
timeFrame: From first dose of study treatment to the date of PD or clinical PD or censoring whichever occurred first (maximum up to 8.3 months)
measure: Part B: Confirmed Investigator Determined PFS According to RECIST v1.1
timeFrame: From first dose of study treatment to the date of PD or clinical PD or censoring whichever occurred first (maximum up to 34.7 months for 1.25 mg/kg and 5.7 months for 1 mg/kg dose level)
measure: Part B: Confirmed Investigator Determined PSA-PFS, for Prostate Cancer
timeFrame: From first dose of study treatment to the date of PD or clinical PD or censoring whichever occurred first (maximum up to 5.7 months)
measure: Part A: Overall Survival (OS)
timeFrame: From first dose of study treatment to the date of death or censoring whichever occurred first (maximum up to 27.5 months)
measure: Part B: Overall Survival
timeFrame: From first dose of study treatment to the date of death or censoring whichever occurred first (maximum up to 37.5 months for 1.25 mg/kg and 20.9 months for 1 mg/kg dose level)
measure: Part A: Area Under the Serum Concentration Time Curve Between Days 0 to 21 (AUC21) of Ladiratuzumab Vedotin
timeFrame: AUC21 is reported on Day 21 using PK concentrations assessed at Pre-dose, end of infusion, 2 hour, 4 hour, 48 hour, 168 hour and 336 hour post dose of Cycle 1 (each cycle = 21 days, LV administered on Day 1 of cycle)
measure: Part A: Maximum Serum Concentration (Cmax) According to Antibody-Drug Conjugate (ADC) Pharmacokinetic Parameters
timeFrame: Cmax during Day 1 to 21 post LV administration on Day 1 was reported using PK concentration assessed at Pre-dose, end of infusion, 2 hour, 4 hour, 48 hour, 168 hour and 336 hour post-dose of LV administration on Day 1 (each cycle = 21 days)
measure: Part A: AUC21 of Total Antibody (TAB)
timeFrame: AUC21 is reported on Day 21 using PK concentrations assessed at Pre-dose, end of infusion, 2 hour, 4 hour, 48 hour, 168 hour and 336 hour post dose of Cycle 1 (each cycle = 21 days, LV administered on Day 1 of cycle)
measure: Part A: Cmax According to TAB Pharmacokinetic Parameters
timeFrame: Cmax during Day 1 to 21 post LV administration on Day 1 was reported using PK concentration assessed at Pre-dose, end of infusion, 2 hour, 4 hour, 48 hour, 168 hour and 336 hour post-dose of LV administration on Day 1 (each cycle = 21 days)
measure: Part A: AUC21 of Monomethyl Auristatin E (MMAE)
timeFrame: AUC21 is reported on Day 21 using PK concentrations assessed at Pre-dose, end of infusion, 2 hour, 4 hour, 48 hour, 168 hour and 336 hour post dose of Cycle 1 (each cycle = 21 days, LV administered on Day 1 of cycle)
measure: Part A: Cmax According to MMAE Pharmacokinetic Parameters
timeFrame: Cmax during Day 1 to 21 post LV administration on Day 1 was reported using PK concentration assessed at Pre-dose, end of infusion, 2 hour, 4 hour, 48 hour, 168 hour and 336 hour post-dose of LV administration on Day 1 (each cycle = 21 days)
measure: Part B: Area Under the Concentration Time Curve Between Day 0 to 7 (AUC7) of ADC
timeFrame: AUC7 is reported at Day 7 using PK concentration assessed at Pre-dose, end of infusion, 2hr, 4hr, 48hr post-dose of LV administration on Day 1; pre-dose PK concentration on Day 8 in Cycle 1 (each cycle=21 days, LV administered on Day 1, 8 and 15 of cycle)
measure: Part B: Cmax According to ADC Pharmacokinetic Parameters
timeFrame: Cmax during Day 1 to 7 post LV administration on Day 1 was reported using PK concentration assessed at Pre-dose, end of infusion, 2 hr, 4 hr, 48 hr post-dose of LV administration on Day 1 (each cycle = 21 days, LV administered on Day 1, 8 and 15 of cycle)
measure: Part B: AUC7 of TAB
timeFrame: AUC7 is reported at Day 7 using PK concentration assessed at Pre-dose, end of infusion, 2hr, 4hr, 48hr post-dose of LV administration on Day 1; pre-dose PK concentration on Day 8 in Cycle 1 (each cycle=21 days, LV administered on Day 1, 8 and 15 of cycle)
measure: Part B: Cmax According to TAB Pharmacokinetic Parameters
timeFrame: Cmax during Day 1 to 7 post LV administration on Day 1 was reported using PK concentration assessed at Pre-dose, end of infusion, 2 hr, 4 hr, 48 hr post-dose of LV administration on Day 1 (each cycle = 21 days, LV administered on Day 1, 8 and 15 of cycle)
measure: Part B: AUC7 OF MMAE
timeFrame: AUC7 is reported at Day 7 using PK concentration assessed at Pre-dose, end of infusion, 2hr, 4hr, 48hr post-dose of LV administration on Day 1; pre-dose PK concentration on Day 8 in Cycle 1 (each cycle=21 days, LV administered on Day 1, 8 and 15 of cycle)
measure: Part B: Cmax According to MMAE Pharmacokinetic Parameters
timeFrame: Cmax during Day 1 to 7 post LV administration on Day 1 was reported using PK concentration assessed at Pre-dose, end of infusion, 2 hr, 4 hr, 48 hr post-dose of LV administration on Day 1 (each cycle= 21 days, LV administered on Day 1, 8 and 15 of cycle)
measure: Part A: Number of Participants With Positive Post-Baseline Antitherapeutic Antibody (ATA) Incidence
timeFrame: From first ATA draw to last ATA draw (maximum up to 8.8 months)
measure: Part B: Number of Participants With Positive Post-Baseline ATA Incidence
timeFrame: From first ATA draw to last ATA draw (maximum up to 22.1 months for 1.25 mg/kg and 5.1 months for 1 mg/kg)
Other outcomes:
Locations:
city: Chandler
country: United States
facility: Ironwood Cancer & Research Centers - Chandler
state: Arizona
city: Los Angeles
country: United States
facility: Adventist Health White Memorial
state: California
city: Santa Rosa
country: United States
facility: Providence Medical Foundation
state: California
city: Norwich
country: United States
facility: Eastern CT Hematology and Oncology Associates
state: Connecticut
city: Jacksonville
country: United States
facility: GenesisCare USA
state: Florida
city: Orlando
country: United States
facility: AdventHealth Cancer Institute
state: Florida
city: Columbus
country: United States
facility: IACT Health
state: Georgia
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Decatur
country: United States
facility: Decatur Memorial Hospital - Illinois
state: Illinois
city: Fort Wayne
country: United States
facility: Fort Wayne Medical Oncology and Hematology
state: Indiana
city: Baltimore
country: United States
facility: University of Maryland
state: Maryland
city: Ann Arbor
country: United States
facility: University of Michigan Comprehensive Cancer Center
state: Michigan
city: Saint Louis Park
country: United States
facility: HealthPartners Institute
state: Minnesota
city: Las Vegas
country: United States
facility: Comprehensive Cancer Centers of Nevada
state: Nevada
city: Paramus
country: United States
facility: Valley Hospital, The / Luckow Pavilion
state: New Jersey
city: Farmington
country: United States
facility: San Juan Oncology Associates
state: New Mexico
city: New York
country: United States
facility: Weill Cornell Medicine
state: New York
city: Stony Brook
country: United States
facility: Stony Brook University Cancer Center
state: New York
city: Pinehurst
country: United States
facility: FirstHealth of the Carolinas
state: North Carolina
city: Canton
country: United States
facility: Gabrail Cancer Center Research, LLC
state: Ohio
city: Portland
country: United States
facility: Providence Portland Medical Center
state: Oregon
city: Greenville
country: United States
facility: Saint Francis Hospital / Bon Secours - South Carolina
state: South Carolina
city: Chattanooga
country: United States
facility: Erlanger Oncology and Hematology
state: Tennessee
city: Nashville
country: United States
facility: Tennessee Oncology-Nashville/Sarah Cannon Research Institute
state: Tennessee
city: Lubbock
country: United States
facility: Joe Arrington Cancer Research and Treatment Center
state: Texas
city: Tyler
country: United States
facility: UT Health East Texas Hope Cancer Center
state: Texas
city: Madison
country: United States
facility: Carbone Cancer Center / University of Wisconsin
state: Wisconsin
city: Bedford Park
country: Australia
facility: Flinders Medical Centre
state: Other
city: Douglas
country: Australia
facility: Townsville Cancer Center
state: Other
city: Frankston
country: Australia
facility: Peninsula and South East Oncology
state: Other
city: Gosford
country: Australia
facility: Central Coast Local Health District (Gosford and Wyong Hospitals)
state: Other
city: Hobart
country: Australia
facility: Royal Hobart Hospital
state: Other
city: Malvern
country: Australia
facility: Cabrini
state: Other
city: Sydney
country: Australia
facility: St Vincents Hospital Sydney
state: Other
city: Wollstonecraft
country: Australia
facility: Melanoma Institute Australia
state: Other
city: Bologna
country: Italy
facility: Azienda Ospedaliero-Universitaria di Bologna Policlinico S. Orsola-Malpighi
state: Other
city: Firenze
country: Italy
facility: Azienda Ospedaliero Universitaria Careggi
state: Other
city: Genova
country: Italy
facility: ASL 3 Genovese Villa Scassi Hospital
state: Other
city: Lucca
country: Italy
facility: San Luca Hospital
state: Other
city: Meldola
country: Italy
facility: Irccs Irst
state: Other
city: Milano
country: Italy
facility: Istituto Europeo di Oncologia
state: Other
city: Milan
country: Italy
facility: Niguarda Ca' Granda Hospital
state: Other
city: Monza
country: Italy
facility: Fondazione IRCCS San Gerardo dei Tintori
state: Other
city: Napoli
country: Italy
facility: Istituto Nazionale Tumori IRCCS Fondazione G. Pascale
state: Other
city: Roma
country: Italy
facility: Policlinico Universitario Agostino Gemelli
state: Other
city: Siena
country: Italy
facility: AOUS Policlinico Le Scotte
state: Other
city: Busan
country: Korea, Republic of
facility: Dong-A University Hospital
state: Other
city: Hwasun
country: Korea, Republic of
facility: Chonnam National University Hwasun Hospital
state: Other
city: Seongnam-si
country: Korea, Republic of
facility: Seoul National University Bundang Hospital
state: Other
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
state: Other
city: Seoul
country: Korea, Republic of
facility: Severance Hospital, Yonsei University Health System
state: Other
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
state: Other
city: Seoul
country: Korea, Republic of
facility: Seoul National University Boramae Medical Center
state: Other
city: Seoul
country: Korea, Republic of
facility: Korea University Guro Hospital
state: Other
city: Suwon-si
country: Korea, Republic of
facility: St. Vincent's Hospital, The Catholic University of Korea
state: Other
city: Suwon-si
country: Korea, Republic of
facility: Ajou University Hospital
state: Other
city: Taichung
country: Taiwan
facility: Taichung Veterans General Hospital
state: Other
city: Tainan
country: Taiwan
facility: National Cheng-Kung University Hospital
state: Other
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
state: Other
city: Taipei
country: Taiwan
facility: Taipei Medical University Hospital
state: Other
city: Glasgow
country: United Kingdom
facility: The Beatson West of Scotland Cancer Centre
state: Other
city: London
country: United Kingdom
facility: The Royal Marsden Hospital
state: Other
city: London
country: United Kingdom
facility: Sarah Cannon Research Institute UK
state: Other
city: London
country: United Kingdom
facility: UCL Cancer Institute
state: Other
city: Manchester
country: United Kingdom
facility: The Christie NHS Foundation Trust
state: Other
city: Sutton
country: United Kingdom
facility: The Royal Marsden Hospital (Surrey)
state: Other
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: