E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10065252 |
E.1.2 | Term | Solid tumor |
E.1.2 | System Organ Class | 100000004864 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
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) |
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E.2.2 | Secondary objectives of the trial |
-Evaluate the safety and tolerability of LV as measured by type, incidence, severity, seriousness, and relatedness of adverse events (AEs) -Evaluate stability and control of disease as measured by disease control rate (DCR) -Evaluate durability of response as measured by duration of response (DOR) -Assess progression-free survival (PFS) -Assess survival as measured by overall survival (OS) -Assess pharmacokinetics (PK) and immunogenicity of LV
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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
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E.4 | Principal 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
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E.5 End points |
E.5.1 | Primary end point(s) |
-Evaluate antitumor activity of LV
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
-Investigator-determined confirmed ORR as measured by RECIST v1.1
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E.5.2 | Secondary end point(s) |
Evaluate the safety and tolerability of LV -Evaluate stability and control of disease -Evaluate durability of response in subjects who respond to LV -Evaluate PFS of subjects treated with LV -Evaluate survival of subjects treated with LV -Assess PK of LV -Assess immunogenicity of LV -Assess biomarkers of biological activity and resistance and predictive biomarkers of response |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
-Type, incidence, severity, seriousness, and relatedness of AEs -Investigator-determined DCR as measured by RECIST v1.1 -Investigator-determined DOR as measured by RECIST v1.1 -Investigator-determined PFS as measured by RECIST v1.1 -OS -Selected PK parameters for LV, total antibody, and MMAE -Incidence of ATAs to LV -Relationship between biomarkers in blood and tumor tissue to efficacy, safety, or other biomarker endpoints following treatment with LV |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | Yes |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 22 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Australia |
Italy |
Korea, Republic of |
Spain |
Taiwan |
United Kingdom |
United States |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 4 |