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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT04032704




Registration number
NCT04032704
Ethics application status
Date submitted
23/07/2019
Date registered
25/07/2019
Date last updated
17/04/2024

Titles & IDs
Public title
A Study of Ladiratuzumab Vedotin in Advanced Solid Tumors
Scientific title
Open-Label Phase 2 Study of Ladiratuzumab Vedotin (LV) for Unresectable Locally Advanced or Metastatic Solid Tumors
Secondary ID [1] 0 0
SGNLVA-005
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Small Cell Lung Cancer 0 0
Non-small Cell Lung Cancer, Squamous 0 0
Non-small Cell Lung Cancer, Non-squamous 0 0
Head and Neck Squamous Cell Carcinoma 0 0
Esophageal Squamous Cell Carcinoma 0 0
Gastric Adenocarcinoma 0 0
Gastroesophageal Junction Adenocarcinoma 0 0
Prostate Cancer 0 0
Melanoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Non melanoma skin cancer
Cancer 0 0 0 0
Kidney
Cancer 0 0 0 0
Lung - Mesothelioma
Cancer 0 0 0 0
Lung - Non small cell
Cancer 0 0 0 0
Lung - Small cell
Cancer 0 0 0 0
Head and neck
Cancer 0 0 0 0
Oesophageal (gullet)

Intervention/exposure
Study type
Interventional(has expanded access)
Description of intervention(s) / exposure
Treatment: Drugs - ladiratuzumab vedotin
Treatment: Drugs - pembrolizumab

Experimental: Part A: Non-randomized LV monotherapy - Monotherapy dosing schedule 1.

Experimental: Part B: Non-randomized LV monotherapy - Monotherapy dosing schedule 2.

Experimental: Part C - Arm 1: Randomized LV monotherapy - Monotherapy dosing schedule 3.

Experimental: Part C - Arm 2: Randomized LV combination therapy - Combination dosing schedule 1.

Experimental: Part C - Arm 3: Randomized LV combination therapy - Combination dosing schedule 2.


Treatment: Drugs: ladiratuzumab vedotin
Intravenous (into the vein; IV) infusion

Treatment: Drugs: pembrolizumab
200mg given by IV on Day 1 of each 21-day cycle
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Confirmed objective response rate (ORR) as determined by investigator according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1)
Timepoint [1] 0 0
Up to approximately 1 year
Primary outcome [2] 0 0
Prostate-specific antigen (PSA) response rate as determined by investigator according to Prostate Cancer Clinical Trials Working Group 3 (PCWG3) criteria (Cohort 7 only)
Timepoint [2] 0 0
Up to approximately 1 year
Secondary outcome [1] 0 0
Number of participants with adverse events (AEs)
Timepoint [1] 0 0
Up to approximately 1 year
Secondary outcome [2] 0 0
Disease control rate (DCR) as determined by investigator according to RECIST v1.1
Timepoint [2] 0 0
Up to approximately 1 year
Secondary outcome [3] 0 0
Duration of response (DOR) as determined by investigator according to RECIST v1.1
Timepoint [3] 0 0
Up to approximately 1 year
Secondary outcome [4] 0 0
PSA-DOR as determined by investigator assessment (Cohort 7 only)
Timepoint [4] 0 0
Up to approximately 1 year
Secondary outcome [5] 0 0
Progression-free survival (PFS) as determined by investigator according to RECIST v1.1
Timepoint [5] 0 0
Up to approximately 1 year
Secondary outcome [6] 0 0
PSA-PFS as determined by investigator assessment (Cohort 7 only)
Timepoint [6] 0 0
Up to approximately 1 year
Secondary outcome [7] 0 0
Overall survival (OS)
Timepoint [7] 0 0
Up to approximately 1 year
Secondary outcome [8] 0 0
Maximum observed concentration (Cmax)
Timepoint [8] 0 0
Up to approximately 1 year
Secondary outcome [9] 0 0
Area under the concentration-time curve (AUC)
Timepoint [9] 0 0
Up to approximately 1 year
Secondary outcome [10] 0 0
Incidence of antitherapeutic antibodies (ATAs) to LV
Timepoint [10] 0 0
Up to approximately 1 year

Eligibility
Key inclusion 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)
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Terminated
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
9/10/2019
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
28/11/2023
Sample size
Target
Accrual to date
Final
205
Recruitment in Australia
Recruitment state(s)
Othe
Recruitment hospital [1] 0 0
Flinders Medical Centre - Bedford Park
Recruitment hospital [2] 0 0
Townsville Cancer Center - Douglas
Recruitment hospital [3] 0 0
Peninsula and South East Oncology - Frankston
Recruitment hospital [4] 0 0
Central Coast Local Health District (Gosford and Wyong Hospitals) - Gosford
Recruitment hospital [5] 0 0
Royal Hobart Hospital - Hobart
Recruitment hospital [6] 0 0
Cabrini - Malvern
Recruitment hospital [7] 0 0
St Vincents Hospital Sydney - Sydney
Recruitment hospital [8] 0 0
Melanoma Institute Australia - Wollstonecraft
Recruitment postcode(s) [1] 0 0
5042 - Bedford Park
Recruitment postcode(s) [2] 0 0
4814 - Douglas
Recruitment postcode(s) [3] 0 0
3199 - Frankston
Recruitment postcode(s) [4] 0 0
2250 - Gosford
Recruitment postcode(s) [5] 0 0
7000 - Hobart
Recruitment postcode(s) [6] 0 0
3144 - Malvern
Recruitment postcode(s) [7] 0 0
2010 - Sydney
Recruitment postcode(s) [8] 0 0
2065 - Wollstonecraft
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Connecticut
Country [4] 0 0
United States of America
State/province [4] 0 0
Florida
Country [5] 0 0
United States of America
State/province [5] 0 0
Georgia
Country [6] 0 0
United States of America
State/province [6] 0 0
Illinois
Country [7] 0 0
United States of America
State/province [7] 0 0
Indiana
Country [8] 0 0
United States of America
State/province [8] 0 0
Maryland
Country [9] 0 0
United States of America
State/province [9] 0 0
Michigan
Country [10] 0 0
United States of America
State/province [10] 0 0
Minnesota
Country [11] 0 0
United States of America
State/province [11] 0 0
Nevada
Country [12] 0 0
United States of America
State/province [12] 0 0
New Jersey
Country [13] 0 0
United States of America
State/province [13] 0 0
New Mexico
Country [14] 0 0
United States of America
State/province [14] 0 0
New York
Country [15] 0 0
United States of America
State/province [15] 0 0
North Carolina
Country [16] 0 0
United States of America
State/province [16] 0 0
Ohio
Country [17] 0 0
United States of America
State/province [17] 0 0
Oregon
Country [18] 0 0
United States of America
State/province [18] 0 0
South Carolina
Country [19] 0 0
United States of America
State/province [19] 0 0
Tennessee
Country [20] 0 0
United States of America
State/province [20] 0 0
Texas
Country [21] 0 0
United States of America
State/province [21] 0 0
Wisconsin
Country [22] 0 0
Italy
State/province [22] 0 0
Other
Country [23] 0 0
Korea, Republic of
State/province [23] 0 0
Other
Country [24] 0 0
Taiwan
State/province [24] 0 0
Other
Country [25] 0 0
United Kingdom
State/province [25] 0 0
Other

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Seagen Inc.
Address
Country
Other collaborator category [1] 0 0
Commercial sector/Industry
Name [1] 0 0
Merck Sharp & Dohme LLC
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/ct2/show/NCT04032704
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Brandon Croft, PharmD
Address 0 0
Seagen Inc.
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT04032704