This study is designed to evaluate safety and antitumor activity of U3-1402 in two parts: Dose Escalation and Dose Expansion. In Dose Escalation, U3-1402 will be evaluated in participants with metastatic or unresectable NSCLC with epidermal growth factor receptor (EGFR) activating mutation after disease progression during/after EGFR tyrosine kinase inhibitor (TKI) therapy. In Dose Expansion, U3-1402 will be evaluated in participants with metastatic or unresectable NSCLC with EGFR activating mutation or squamous or non-squamous NSCLC (ie, without EGFR-activating mutations) with disease progression during/after systemic treatment for locally advanced or metastatic disease.
Name: U3-1402
Description: Evaluated using RECIST 1.1
Measure: Overall response rate (ORR) assessed by Blinded Independent Central Review (BICR) Committee in the dose expansion period Time: Approximately within 36 monthsDescription: Evaluated using RECIST 1.1
Measure: Overall response rate (ORR) in the dose escalation period Time: Approximately within 36 monthsDescription: Evaluated using RECIST 1.1
Measure: Overall response rate (ORR) in the dose expansion period Time: Approximately within 36 monthsAllocation: Non-Randomized
Sequential Assignment
There are 3 SNPs
Inclusion Criteria for both Dose Escalation and Dose Expansion: 1. Has locally advanced or metastatic NSCLC, not amenable to curative surgery or radiation 2. Has at least one measurable lesion per RECIST version 1.1 3. Has Eastern Cooperative Oncology Group performance status of 0 or 1 at Screening Inclusion Criteria for Dose Escalation only: 1. Has histologically or cytologically documented adenocarcinoma NSCLC 2. Has acquired resistance to EGFR TKI according to the Jackman criteria (PMID: 19949011) 1. Historical confirmation that the tumor harbors an epidermal growth factor receptor (EGFR) mutation known to be associated with EGFR tyrosine kinase inhibitor (TKI) sensitivity (including G719X, exon 19 deletion, L858R, L861Q) 2. Has experienced clinical benefit from an EGFR TKI, followed by systemic progression of disease [Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1] or World Health Organization (WHO)] while on continuous treatment with an EGFR TKI 3. Is currently receiving and able to discontinue erlotinib, gefinitib, afatinib, or osimertinib 4. Has been receiving erlotinib, gefitinib, afatinib, or osimertinib for at least 6 weeks with well-controlled related toxicities less than Grade 3 in severity at the time of Screening 5. Has radiological documentation of disease progression while receiving continuous treatment with erlotinib, gefitinib, afatinib, or osimertinib 6. --- L858R ---
3. Has documentation of EGFR-activating mutation(s) detected from tumor tissue: G719X, exon deletion 19, L858R, or L861Q. --- L858R ---
Has clinically significant corneal disease Additional Exclusion Criteria for Dose Expansion Cohort 2: 1. Has documentation of one or more of the following EGFR-activating mutations: G719X, exon 19 deletion, L858R, or L861Q Inclusion Criteria for both Dose Escalation and Dose Expansion: 1. Has locally advanced or metastatic NSCLC, not amenable to curative surgery or radiation 2. Has at least one measurable lesion per RECIST version 1.1 3. Has Eastern Cooperative Oncology Group performance status of 0 or 1 at Screening Inclusion Criteria for Dose Escalation only: 1. Has histologically or cytologically documented adenocarcinoma NSCLC 2. Has acquired resistance to EGFR TKI according to the Jackman criteria (PMID: 19949011) 1. Historical confirmation that the tumor harbors an epidermal growth factor receptor (EGFR) mutation known to be associated with EGFR tyrosine kinase inhibitor (TKI) sensitivity (including G719X, exon 19 deletion, L858R, L861Q) 2. Has experienced clinical benefit from an EGFR TKI, followed by systemic progression of disease [Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1] or World Health Organization (WHO)] while on continuous treatment with an EGFR TKI 3. Is currently receiving and able to discontinue erlotinib, gefinitib, afatinib, or osimertinib 4. Has been receiving erlotinib, gefitinib, afatinib, or osimertinib for at least 6 weeks with well-controlled related toxicities less than Grade 3 in severity at the time of Screening 5. Has radiological documentation of disease progression while receiving continuous treatment with erlotinib, gefitinib, afatinib, or osimertinib 6. --- L858R ---
Has clinically significant corneal disease Additional Exclusion Criteria for Dose Expansion Cohort 2: 1. Has documentation of one or more of the following EGFR-activating mutations: G719X, exon 19 deletion, L858R, or L861Q Inclusion Criteria for both Dose Escalation and Dose Expansion: 1. Has locally advanced or metastatic NSCLC, not amenable to curative surgery or radiation 2. Has at least one measurable lesion per RECIST version 1.1 3. Has Eastern Cooperative Oncology Group performance status of 0 or 1 at Screening Inclusion Criteria for Dose Escalation only: 1. Has histologically or cytologically documented adenocarcinoma NSCLC 2. Has acquired resistance to EGFR TKI according to the Jackman criteria (PMID: 19949011) 1. Historical confirmation that the tumor harbors an epidermal growth factor receptor (EGFR) mutation known to be associated with EGFR tyrosine kinase inhibitor (TKI) sensitivity (including G719X, exon 19 deletion, L858R, L861Q) 2. Has experienced clinical benefit from an EGFR TKI, followed by systemic progression of disease [Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1] or World Health Organization (WHO)] while on continuous treatment with an EGFR TKI 3. Is currently receiving and able to discontinue erlotinib, gefinitib, afatinib, or osimertinib 4. Has been receiving erlotinib, gefitinib, afatinib, or osimertinib for at least 6 weeks with well-controlled related toxicities less than Grade 3 in severity at the time of Screening 5. Has radiological documentation of disease progression while receiving continuous treatment with erlotinib, gefitinib, afatinib, or osimertinib 6. --- L858R --- --- L861Q --- --- L858R ---
Has clinically significant corneal disease Additional Exclusion Criteria for Dose Expansion Cohort 2: 1. Has documentation of one or more of the following EGFR-activating mutations: G719X, exon 19 deletion, L858R, or L861Q Non-Small Cell Lung Cancer (NSCLC) Lung Neoplasms Carcinoma, Non-Small-Cell Lung The primary objectives are: - For Dose Escalation, to assess the safety and tolerability of U3-1402 in the study population and to determine the recommended dose for expansion (RDE) of U3-1402 in the study population - For Dose Expansion, to investigate the antitumor activity of U3-1402 The number of treatment cycles is not fixed in this study. --- L858R ---
Inclusion Criteria for both Dose Escalation and Dose Expansion: 1. Has locally advanced or metastatic NSCLC, not amenable to curative surgery or radiation 2. Has at least one measurable lesion per RECIST version 1.1 3. Has Eastern Cooperative Oncology Group performance status of 0 or 1 at Screening Inclusion Criteria for Dose Escalation only: 1. Has histologically or cytologically documented adenocarcinoma NSCLC 2. Has acquired resistance to EGFR TKI according to the Jackman criteria (PMID: 19949011) 1. Historical confirmation that the tumor harbors an epidermal growth factor receptor (EGFR) mutation known to be associated with EGFR tyrosine kinase inhibitor (TKI) sensitivity (including G719X, exon 19 deletion, L858R, L861Q) 2. Has experienced clinical benefit from an EGFR TKI, followed by systemic progression of disease [Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1] or World Health Organization (WHO)] while on continuous treatment with an EGFR TKI 3. Is currently receiving and able to discontinue erlotinib, gefinitib, afatinib, or osimertinib 4. Has been receiving erlotinib, gefitinib, afatinib, or osimertinib for at least 6 weeks with well-controlled related toxicities less than Grade 3 in severity at the time of Screening 5. Has radiological documentation of disease progression while receiving continuous treatment with erlotinib, gefitinib, afatinib, or osimertinib 6. --- L858R --- --- L861Q ---
3. Has documentation of EGFR-activating mutation(s) detected from tumor tissue: G719X, exon deletion 19, L858R, or L861Q. --- L858R --- --- L861Q ---
Has clinically significant corneal disease Additional Exclusion Criteria for Dose Expansion Cohort 2: 1. Has documentation of one or more of the following EGFR-activating mutations: G719X, exon 19 deletion, L858R, or L861Q Inclusion Criteria for both Dose Escalation and Dose Expansion: 1. Has locally advanced or metastatic NSCLC, not amenable to curative surgery or radiation 2. Has at least one measurable lesion per RECIST version 1.1 3. Has Eastern Cooperative Oncology Group performance status of 0 or 1 at Screening Inclusion Criteria for Dose Escalation only: 1. Has histologically or cytologically documented adenocarcinoma NSCLC 2. Has acquired resistance to EGFR TKI according to the Jackman criteria (PMID: 19949011) 1. Historical confirmation that the tumor harbors an epidermal growth factor receptor (EGFR) mutation known to be associated with EGFR tyrosine kinase inhibitor (TKI) sensitivity (including G719X, exon 19 deletion, L858R, L861Q) 2. Has experienced clinical benefit from an EGFR TKI, followed by systemic progression of disease [Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1] or World Health Organization (WHO)] while on continuous treatment with an EGFR TKI 3. Is currently receiving and able to discontinue erlotinib, gefinitib, afatinib, or osimertinib 4. Has been receiving erlotinib, gefitinib, afatinib, or osimertinib for at least 6 weeks with well-controlled related toxicities less than Grade 3 in severity at the time of Screening 5. Has radiological documentation of disease progression while receiving continuous treatment with erlotinib, gefitinib, afatinib, or osimertinib 6. --- L858R --- --- L861Q ---
Has clinically significant corneal disease Additional Exclusion Criteria for Dose Expansion Cohort 2: 1. Has documentation of one or more of the following EGFR-activating mutations: G719X, exon 19 deletion, L858R, or L861Q Inclusion Criteria for both Dose Escalation and Dose Expansion: 1. Has locally advanced or metastatic NSCLC, not amenable to curative surgery or radiation 2. Has at least one measurable lesion per RECIST version 1.1 3. Has Eastern Cooperative Oncology Group performance status of 0 or 1 at Screening Inclusion Criteria for Dose Escalation only: 1. Has histologically or cytologically documented adenocarcinoma NSCLC 2. Has acquired resistance to EGFR TKI according to the Jackman criteria (PMID: 19949011) 1. Historical confirmation that the tumor harbors an epidermal growth factor receptor (EGFR) mutation known to be associated with EGFR tyrosine kinase inhibitor (TKI) sensitivity (including G719X, exon 19 deletion, L858R, L861Q) 2. Has experienced clinical benefit from an EGFR TKI, followed by systemic progression of disease [Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1] or World Health Organization (WHO)] while on continuous treatment with an EGFR TKI 3. Is currently receiving and able to discontinue erlotinib, gefinitib, afatinib, or osimertinib 4. Has been receiving erlotinib, gefitinib, afatinib, or osimertinib for at least 6 weeks with well-controlled related toxicities less than Grade 3 in severity at the time of Screening 5. Has radiological documentation of disease progression while receiving continuous treatment with erlotinib, gefitinib, afatinib, or osimertinib 6. --- L858R --- --- L861Q --- --- L858R --- --- L861Q ---
Has clinically significant corneal disease Additional Exclusion Criteria for Dose Expansion Cohort 2: 1. Has documentation of one or more of the following EGFR-activating mutations: G719X, exon 19 deletion, L858R, or L861Q Non-Small Cell Lung Cancer (NSCLC) Lung Neoplasms Carcinoma, Non-Small-Cell Lung The primary objectives are: - For Dose Escalation, to assess the safety and tolerability of U3-1402 in the study population and to determine the recommended dose for expansion (RDE) of U3-1402 in the study population - For Dose Expansion, to investigate the antitumor activity of U3-1402 The number of treatment cycles is not fixed in this study. --- L858R --- --- L861Q ---
Is willing to provide archival tumor tissue from a biopsy performed within 6 months of progression during treatment with erlotinib, gefitinib, afatinib, or osimertinib OR has at least one lesion, not previously irradiated, amenable to core biopsy and is willing to undergo screening tumor biopsy 7. Demonstrates absence of EGFR T790M mutation if treated with erlotinib, gefitinib, or afatinib. --- T790M ---
Participants with EGFR T790M mutation following treatment with erlotinib, gefitinib afatinib, or dacomitinib must have received and have documentation of radiological disease progression following treatment with osimertinib unless unable or unwilling. --- T790M ---