lungcarcinoma Non small cell lung cancer
Conditions
Interventions
Participants will receive IV telisotuzumab vedotin monotherapy every 2 weeks or
IV telisotuzumab vedotin every 2 weeks in combination with osimertinib until
meeting the study drug discontinuation cr
Sponsors
AbbVie B.V.
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: 1. Subject must be >= 18 years of age 2. Subject must have advanced NSCLC that is not amenable to surgical resection or other approved therapeutic options that have demonstrated clinical benefit. -Subjects who have refused, are considered ineligible for or are intolerant of standard therapy are eligible -Based on evidence gathered in this study or from external sources, the Sponsor in consultation with the Investigators, may decide to limit to specific tumor histology. - For Monotherapy dose-escalation - Subject with advanced solid tumors - For Monotherapy dose-expansion and Combination Arms A + D - Subject must have tumor with c-Met overexpression, MET exon 14 skip mutation or MET amplification. 3. Subject has an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 2. For *monotherapy expansion cohort 1.6 Q2W*, subjects have an ECOG performance status of 0 or 1. 4. Subject must have measurable disease per RECIST version 1.1 (Appendix C) 5. Subject has fresh and/or archived diagnostic formalin-fixed paraffin embedded (FFPE) tumor tissue available for analysis 6. Subject has adequate bone marrow, renal, and hepatic function 7. A negative serum pregnancy test for all female subjects of childbearing potential at the screening visit and a negative urine pregnancy test for all female subjects of childbearing potential at baseline prior to the first dose of study drug (for details on contraception refer to Section 5.2.1) 8. Subject is capable of understanding and complying with parameters as outlined in the protocol and able to sign informed consent, approved by an Institutional Review Board (IRB) prior to the initiation of any screening or study-specific procedures. Additional Inclusion Criteria for Subjects Enrolled on the Combination Therapy Phase Subjects in the combination therapy arms A and D must meet the above inclusion criteria and be eligible to receive erlotinib, or nivolumab per locally approved labeling, or at the discretion of the Investigator in consultation with the Medical Monitor -Subjects enrolled in the combination therapy phase Arm E must satisfy the above inclusion criteria numbers 1 - 4, 6 - 8 and the following: •Subject must have metastatic/locally advanced nonsquamous NSCLC with documented EGFR mutations del19 or L858R, with or without T790M mutation, and none of the EGFR mutations known to be resistant to osimertinib. •Subject must have received at least 1 but no more than 2 prior regimens, one of which must have contained osimertinib. Subject must have had disease progression while on osimertinib. Only 1 prior regimen may have contained chemotherapy. From amendment 15 and later, and for the purpose of this eligibility criterion, consecutive EGFR TKIs will count as 1 regimen. • Subject must have available post-osimertinib progression tumor tissue for central c-Met immunohistochemistry (IHC) testing. In cases where it is not possible to obtain a post-osimertinib progression biopsy, archival tissue may be allowed. Additional Inclusion Criteria for Subjects Enrolled in the *monotherapy expansion cohort 1.6 Q2W* Subjects must satisfy the above inclusion criteria 1-4 , 6-8, and also the following: • Subjects must have locally advanced or metastatic, non-squamous, EGFR wild type (site documented EGFR status), c-Met+ (as
Exclusion criteria
Exclusion criteria: •Subject has received radiation therapy to the lung = Grade 2 from prior anticancer therapy except for alopecia or anemia. •Subject has had major surgery within 21 days prior to the first dose of ABBV-399. •Subject has a clinically significant condition(s) •Subject has history of major immunologic reaction to any IgG containing agent. •Subject has any medical condition which in the opinion of the Investigator or Medical Monitor places the subject at an unacceptably high risk for toxicities. •Subject is a lactating or pregnant female. •Subjects with known active COVID-19 infection, subjects with signs/symptoms associated with COVID-19 infection or known exposure to a confirmed case of COVID-19 infection during 14 days prior to Screening: must be screen failed and may only rescreen after they have recovered from COVID-19 or they are no longer considered contagious, per investigator assessment. Additional Exclusion Criteria for Subjects Enrolled on the Combination Therapy Phase •Subjects enrolled on the combination therapy phase must satisfy the above exclusion criteria and also the following: -Subjects may not receive ABBV-399 in combination with osimertinib, erlotinib, or nivolumab if they have any medical condition which in the opinion of the Investigator places the subject at an unacceptably high risk for toxicities from the combination. Subjects may not receive nivolumab if they have * Active autoimmune disease with exceptions of vitiligo, type I diabetes mellitus, hypothyroidism and psoriasis * Used systemic corticosteroids (> 10 mg daily prednisone or equivalent) or other immunosuppressive medications within 14 days of study drug administration, with exception of inhaled, locally injected or topical steroids * Known immunosuppressive disease, for example human immunodeficiency virus infection or history of bone marrow transplant or chronic lymphocytic leukemi
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| - Safety and tolerability will be assessed by evaluating adverse events (AE), physical examinations, and changes in laboratory data and vital signs throughout the entire study. - Blood samples for assay of telisotuzumab vedotin, Total ABT-700 and free MMAE drug levels will be used to evaluate PK parameters. Blood samples for antidrug antibody (ADA) and neutralizing ADA (nADA) will be collected at designated time points throughout the study and ADA/nADA will be correlated with PK and safety outcomes. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary: Objective Response Rate (ORR) (determined using RECIST version 1.1) Progression-Free Survival (PFS) Duration of Overall Response (DOR) Exploratory: Plasma, serum, and tissues samples (archived/re-biopsy or pre- and on-treatment fresh biopsy and post-progression) will be collected during the study. | — |
Countries
Netherlands
Outcome results
None listed