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Phase 2 Study of LV in Advanced Solid Tumors

Phase 1
Conditions
Multiple Solid Tumors
MedDRA version: 21.1Level: LLTClassification code 10065252Term: Solid tumorSystem Organ Class: 100000004864
Therapeutic area: Diseases [C] - Cancer [C04]
Registration Number
EUCTR2019-001946-17-GB
Lead Sponsor
Seattle Genetics, Inc.
Brief Summary

Not available

Detailed Description

Not available

Recruitment & Eligibility

Status
Authorised-recruitment may be ongoing or finished
Sex
All
Target Recruitment
264
Inclusion Criteria

All Cohorts of Part A and Part B
•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
•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
a. Participants must have progressed during or after a platinum based combination therapy administered for the treatment of metastatic disease
b. 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.
•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
a. Participants must have progressed during or after a platinumbased combination therapy administered for the treatment of metastatic disease
b. 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.
•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
a. Disease progression after treatment with a platinum-containing regimen for recurrent/metastatic disease; or
b. 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

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 158
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 105

Exclusion Criteria

All Cohorts of Part A and Part B
•Active concurrent malignancy or a previous malignancy within the past 3 years
•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

Study & Design

Study Type
Interventional clinical trial of medicinal product
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
Main Objective: Evaluate antitumor activity of LV as measured by investigator-determined confirmed objective response rate (ORR) using Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1);Secondary Objective: -Evaluate the safety and tolerability of LV as measured by type, incidence, severity, seriousness, and relatedness of adverse events (AEs)<br>-Evaluate stability and control of disease as measured by disease control rate (DCR)<br>-Evaluate durability of response as measured by duration of response (DOR)<br>-Assess progression-free survival (PFS)<br>-Assess survival as measured by overall survival (OS)<br>-Assess pharmacokinetics (PK) and immunogenicity of LV<br>;Primary end point(s): -Evaluate antitumor activity of LV<br>;Timepoint(s) of evaluation of this end point: -Investigator-determined confirmed ORR as measured by RECIST v1.1<br>
Secondary Outcome Measures
NameTimeMethod
Secondary end point(s): Evaluate the safety and tolerability of LV<br>-Evaluate stability and control of disease<br>-Evaluate durability of response in subjects who respond to LV<br>-Evaluate PFS of subjects treated with LV<br>-Evaluate survival of subjects treated with LV<br>-Assess PK of LV<br>-Assess immunogenicity of LV<br>-Assess biomarkers of biological activity and resistance and predictive biomarkers of response;Timepoint(s) of evaluation of this end point: -Type, incidence, severity, seriousness, and relatedness of AEs<br>-Investigator-determined DCR as measured by RECIST v1.1<br>-Investigator-determined DOR as measured by RECIST v1.1<br>-Investigator-determined PFS as measured by RECIST v1.1<br>-OS<br>-Selected PK parameters for LV, total antibody, and MMAE<br>-Incidence of ATAs to LV<br>-Relationship between biomarkers in blood and tumor tissue to efficacy, safety, or other biomarker endpoints following treatment with LV
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