A Study of Ladiratuzumab Vedotin in Advanced Solid Tumors

Prostate Cancer Clinical Trial

Official title:

Open-Label Phase 2 Study of Ladiratuzumab Vedotin (LV) for Unresectable Locally Advanced or Metastatic Solid Tumors

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04032704
• Other study ID #: SGNLVA-005
• Status: Terminated
• Phase: Phase 2
• Start date: October 9, 2019
• Est. completion date: November 28, 2023

Study information

• Verified date: April 2024
• Source: Seagen Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 205
• Est. completion date: November 28, 2023
• Est. primary completion date: November 28, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Adenocarcinoma
• Carcinoma
• Carcinoma, Non-Small-Cell Lung
• Carcinoma, Squamous Cell
• Esophageal Squamous Cell Carcinoma
• Gastric Adenocarcinoma
• Gastroesophageal Junction Adenocarcinoma
• Head and Neck Squamous Cell Carcinoma
• Lung Neoplasms
• Melanoma
• Non-small Cell Lung Cancer, Non-squamous
• Non-small Cell Lung Cancer, Squamous
• Prostate Cancer
• Small Cell Lung Cancer
• Small Cell Lung Carcinoma
• Squamous Cell Carcinoma of Head and Neck

Intervention

Drug:
• ladiratuzumab vedotin
Intravenous (into the vein; IV) infusion
• pembrolizumab
200mg given by IV on Day 1 of each 21-day cycle

Locations

Country	Name	City	State
Australia	Flinders Medical Centre	Bedford Park	Other
Australia	Townsville Cancer Center	Douglas	Other
Australia	Peninsula and South East Oncology	Frankston	Other
Australia	Central Coast Local Health District (Gosford and Wyong Hospitals)	Gosford	Other
Australia	Royal Hobart Hospital	Hobart	Other
Australia	Cabrini	Malvern	Other
Australia	St Vincents Hospital Sydney	Sydney	Other
Australia	Melanoma Institute Australia	Wollstonecraft	Other
Italy	Azienda Ospedaliero-Universitaria di Bologna Policlinico S. Orsola-Malpighi	Bologna	Other
Italy	Azienda Ospedaliero Universitaria Careggi	Firenze	Other
Italy	ASL 3 Genovese Villa Scassi Hospital	Genova	Other
Italy	San Luca Hospital	Lucca	Other
Italy	Irccs Irst	Meldola	Other
Italy	Niguarda Ca' Granda Hospital	Milan	Other
Italy	Istituto Europeo di Oncologia	Milano	Other
Italy	Fondazione IRCCS San Gerardo dei Tintori	Monza	Other
Italy	Istituto Nazionale Tumori IRCCS Fondazione G. Pascale	Napoli	Other
Italy	Policlinico Universitario Agostino Gemelli	Roma	Other
Italy	AOUS Policlinico Le Scotte	Siena	Other
Korea, Republic of	Dong-A University Hospital	Busan	Other
Korea, Republic of	Chonnam National University Hwasun Hospital	Hwasun	Other
Korea, Republic of	Seoul National University Bundang Hospital	Seongnam-si	Other
Korea, Republic of	Korea University Guro Hospital	Seoul	Other
Korea, Republic of	Samsung Medical Center	Seoul	Other
Korea, Republic of	Seoul National University Boramae Medical Center	Seoul	Other
Korea, Republic of	Seoul National University Hospital	Seoul	Other
Korea, Republic of	Severance Hospital, Yonsei University Health System	Seoul	Other
Korea, Republic of	Ajou University Hospital	Suwon-si	Other
Korea, Republic of	St. Vincent's Hospital, The Catholic University of Korea	Suwon-si	Other
Taiwan	Taichung Veterans General Hospital	Taichung	Other
Taiwan	National Cheng-Kung University Hospital	Tainan	Other
Taiwan	National Taiwan University Hospital	Taipei	Other
Taiwan	Taipei Medical University Hospital	Taipei	Other
United Kingdom	The Beatson West of Scotland Cancer Centre	Glasgow	Other
United Kingdom	Sarah Cannon Research Institute UK	London	Other
United Kingdom	The Royal Marsden Hospital	London	Other
United Kingdom	UCL Cancer Institute	London	Other
United Kingdom	The Christie NHS Foundation Trust	Manchester	Other
United Kingdom	The Royal Marsden Hospital (Surrey)	Sutton	Other
United States	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan
United States	University of Maryland	Baltimore	Maryland
United States	Gabrail Cancer Center Research, LLC	Canton	Ohio
United States	Ironwood Cancer & Research Centers - Chandler	Chandler	Arizona
United States	Erlanger Oncology and Hematology	Chattanooga	Tennessee
United States	Northwestern University	Chicago	Illinois
United States	IACT Health	Columbus	Georgia
United States	Decatur Memorial Hospital - Illinois	Decatur	Illinois
United States	San Juan Oncology Associates	Farmington	New Mexico
United States	Fort Wayne Medical Oncology and Hematology	Fort Wayne	Indiana
United States	Saint Francis Hospital / Bon Secours - South Carolina	Greenville	South Carolina
United States	GenesisCare USA	Jacksonville	Florida
United States	Comprehensive Cancer Centers of Nevada	Las Vegas	Nevada
United States	Adventist Health White Memorial	Los Angeles	California
United States	Joe Arrington Cancer Research and Treatment Center	Lubbock	Texas
United States	Carbone Cancer Center / University of Wisconsin	Madison	Wisconsin
United States	Tennessee Oncology-Nashville/Sarah Cannon Research Institute	Nashville	Tennessee
United States	Weill Cornell Medicine	New York	New York
United States	Eastern CT Hematology and Oncology Associates	Norwich	Connecticut
United States	AdventHealth Cancer Institute	Orlando	Florida
United States	Valley Hospital, The / Luckow Pavilion	Paramus	New Jersey
United States	FirstHealth of the Carolinas	Pinehurst	North Carolina
United States	Providence Portland Medical Center	Portland	Oregon
United States	HealthPartners Institute	Saint Louis Park	Minnesota
United States	Providence Medical Foundation	Santa Rosa	California
United States	Stony Brook University Cancer Center	Stony Brook	New York
United States	UT Health East Texas Hope Cancer Center	Tyler	Texas

Sponsors (2)

Lead Sponsor	Collaborator
Seagen Inc.	Merck Sharp & Dohme LLC

Countries where clinical trial is conducted

United States,  Australia,  Italy,  Korea, Republic of,  Taiwan,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Confirmed objective response rate (ORR) as determined by investigator according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1)	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.	Up to approximately 1 year
Primary	Prostate-specific antigen (PSA) response rate as determined by investigator according to Prostate Cancer Clinical Trials Working Group 3 (PCWG3) criteria (Cohort 7 only)	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.	Up to approximately 1 year
Secondary	Number of participants with adverse events (AEs)	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.	Up to approximately 1 year
Secondary	Disease control rate (DCR) as determined by investigator according to RECIST v1.1	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.	Up to approximately 1 year
Secondary	Duration of response (DOR) as determined by investigator according to RECIST v1.1	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.	Up to approximately 1 year
Secondary	PSA-DOR as determined by investigator assessment (Cohort 7 only)	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	Up to approximately 1 year
Secondary	Progression-free survival (PFS) as determined by investigator according to RECIST v1.1	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.	Up to approximately 1 year
Secondary	PSA-PFS as determined by investigator assessment (Cohort 7 only)	PSA-PFS is defined as the time from the start of study treatment to first occurrence of PSA progression or death, whichever comes first	Up to approximately 1 year
Secondary	Overall survival (OS)	OS is defined as the time from the start of study treatment to date of death due to any cause.	Up to approximately 1 year
Secondary	Maximum observed concentration (Cmax)	Pharmacokinetic (PK) endpoint of LV	Up to approximately 1 year
Secondary	Area under the concentration-time curve (AUC)	PK endpoint of LV	Up to approximately 1 year
Secondary	Incidence of antitherapeutic antibodies (ATAs) to LV		Up to approximately 1 year