Introduction:Telisotuzumab vedotin (Teliso-V) is a c-Met-directed antibody-drug conjugate comprising the monoclonal antibody telisotuzumab and the monomethyl auristatin E payload. Primary analysis of the phase 2 LUMINOSITY trial (NCT03539536) revealed Teliso-V monotherapy 1.9 mg/kg elicited durable responses and had generally manageable safety in patients with locally advanced or metastatic c-Met protein overexpressing, EGFR wild-type, nonsquamous NSCLC. We present updated outcomes with approximately 6 months longer follow-up and explore the impact of previous therapies. Methods:Patients (≥18 y; had previous therapy including ≤1 chemotherapy) received 1.9 mg/kg Teliso-V every 2 weeks. c-Met protein overexpression (clinical trial assay for MET [SP44] [Roche]) was defined as greater than or equal to 25% tumor cells with 3+ staining intensity (c-Met high: ≥50% 3+; c-Met intermediate: 25 to <50% 3+). Primary end point was the overall response rate by independent central review per the Response Evaluation Criteria in Solid Tumors version 1.1. Results:As of February 21, 2024, 172 patients received at least one dose of Teliso-V; 168 patients (c-Met high, n = 84; c-Met intermediate, n = 84) were evaluable for efficacy. The overall response rate was 29.2% (95% confidence interval [CI]: 22.4-36.7; c-Met high, 34.5% [24.5-45.7]; c-Met intermediate, 23.8% [15.2-34.3]). Median duration of response was 7.2 months (95% CI: 5.5-11.0; c-Met high, 7.2 [95% CI: 4.2-12.0]; c-Met intermediate, 7.2 [95% CI: 4.7-11.5]). Previous therapy (platinum, immune checkpoint inhibitors, or both) did not impact efficacy outcomes. The most common treatment-related adverse event was peripheral sensory neuropathy (any-grade: 31%; grade ≥3: 7%). Conclusions:Teliso-V monotherapy 1.9 mg/kg elicited durable responses, irrespective of the type of previous therapy received, and maintained a manageable safety profile in patients with c-Met protein overexpressing EGFR wild-type, nonsquamous NSCLC. ClinicalTrialsgov ID number:NCT03539536.
PURPOSE:Transitions in leadership within pharmacy residency programs can impact the continuity, quality, and regulatory compliance of a program. There is a gap in the literature regarding best practices for transitioning between outgoing and incoming residency program directors (RPDs). The objective of this project was to describe and evaluate the process used to longitudinally transition the RPD role of an American Society of Health-System Pharmacists (ASHP)-accredited residency program. SUMMARY:The transition process was described using a systematic approach to retrospectively reconstruct core transition elements through a review of relevant documents and materials from the 12-month transition process. Materials were reviewed and items categorized via consensus of the study team. The effectiveness of the developed RPD transition process was evaluated by examining program-specific metrics before, during, and following the transition. Based on this review, a transition timeline identifying key transition checkpoints and a transition-specific task list were created. Quality indicators during the transition were generally positive: The number of applicants was maintained, the percentage of on-time summative evaluations increased, the percentage of on-time quarterly development plans increased, and the percentage of on-time initial development plans decreased. CONCLUSION:A structured plan for the transition from outgoing to incoming RPD appeared to allow for quality maintenance and smooth transition of a pharmacy residency program. Identified factors that facilitated a smooth transition included leveraging RPD-specific skill sets and the openness of incoming and outgoing RPDs to suggested program adjustments or improvements.
BACKGROUND:Chronic axial spinal pain is a major contributor to disability and healthcare expenditures, with facet joints recognized as one of the established sources of pain. OBJECTIVE:To provide evidence-based guidance in performing diagnostic and therapeutic facet joint interventions. METHODS:A multidisciplinary panel of experts from various medical and pharmaceutical disciplines, convened by the American Society of Interventional Pain Physicians (ASIPP), reviewed the available evidence, considered patient perspectives, and formulated recommendations for facet joint interventions in the management of chronic pain.The methodology included the development of key questions with evidence-based statements and recommendations. Grading of the evidence and recommendations followed a modified approach described by ASIPP, the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology, and the Agency for Healthcare Research and Quality (AHRQ) methods for grading strength of recommendations. The evidence review included existing guidelines, systematic reviews, comprehensive reviews, randomized controlled trials (RCTs), and observational studies evaluating the effectiveness and safety of facet joint interventions in chronic pain management.In the development of consensus statements and guidelines, a modified Delphi technique was utilized to minimize bias related to group interactions. Panelists without a primary conflict of interest voted on approval of specific guideline statements. Each panelist was permitted to suggest revisions to guideline wording and provide additional qualifying remarks or comments regarding implementation of the guidelines in clinical practice. To achieve consensus and inclusion in the final guidelines, each guideline statement required at least 80% agreement among eligible panel members without a primary conflict of interest. RESULTS:A total of 48 authors participated in the development of these guidelines, of whom 39 participated in the voting process. A total of 37 recommendations were developed, with 100% acceptance for all items. The Summary of Recommendations is presented separately. These recommendations addressed diagnostic, therapeutic, and special considerations related to facet joint interventions. For diagnostic and therapeutic interventions, the level of evidence ranged from II to III, with moderate to strong recommendations. For special considerations and safety assessments, the level of evidence ranged from II to V. The evidence provided recommendations regarding diagnosis, treatment, sedation, concurrent antithrombotic therapy, and precautions required in special clinical circumstances. LIMITATIONS:The limitations of these guidelines include a paucity of high-quality studies in some aspects of diagnosis and therapy. CONCLUSION:These guidelines for facet joint interventions were developed through a comprehensive review of the literature, including methodologic quality assessment and determination of the level of evidence and strength of recommendations. DISCLAIMER:These guidelines are based on the best available evidence and do not constitute inflexible treatment recommendations. Due to the changing body of evidence, this document is not intended to be a "standard of care."
8618 Background: Telisotuzumab vedotin (Teliso-V) is a c-Met–directed antibody-drug conjugate comprising the mAb telisotuzumab and the microtubule polymerization inhibitor monomethyl auristatin E. In the phase 2 LUMINOSITY trial (NCT03539536), Teliso-V monotherapy 1.9 mg/kg showed durable responses and a generally manageable safety profile in patients (pts) with c-Met protein–overexpressing (OE) non-squamous (NSQ) EGFR -wildtype (WT) non-small cell lung cancer (NSCLC). Herein we present an analysis of efficacy outcomes according to prior platinum or prior platinum and immune checkpoint inhibitor (ICI)-based therapies. Methods: Pts (≥18 years) with locally advanced/metastatic c-Met protein–OE NSQ EGFR -WT NSCLC who had ≤2 prior lines of therapy, including ≤1 line of chemotherapy, were treated with 1.9 mg/kg Teliso-V Q2W. c-Met protein overexpression (by immunohistochemistry clinical trial assay for MET [SP44] [Roche]) was defined as ≥25% tumor cells with 3+ staining intensity (high: ≥50% 3+; intermediate [int]: 25 to <50% 3+). The primary endpoint was overall response rate (ORR) by independent central review per RECIST v1.1. Results: As of 21 Feb 2024, 172 pts received ≥1 dose of Teliso-V and 168 pts were included in efficacy analyses (c-Met high, n=84; c-Met int, n=84). In the c-Met OE total population, 97.6% of pts received prior platinum and 78.6% received prior platinum + ICI. Efficacy data for pts with prior platinum and platinum + ICI therapies are shown in the Table. Among the 172 dosed pts, the most common any-grade treatment-related adverse events (TRAEs) were peripheral sensory neuropathy (31%), peripheral edema (16%), and fatigue (14%). The most common grade ≥3 TRAE was peripheral sensory neuropathy (7%). Conclusions: This analysis demonstrated that Teliso-V elicited durable responses in pts with c-Met protein–OE NSQ EGFR -WT NSCLC regardless of whether they had received prior platinum or platinum + ICI therapies; the efficacy outcomes in these subgroups were consistent with those in the overall pt population. Clinical trial information: NCT03539536 . Platinum Platinum + ICI Overall ORR, a n/N (%) [95% CI] c-Met OE total c-Met high c-Met int 48/164 (29.3) [22.4, 36.9]28/81 (34.6) [24.3, 46.0]20/83 (24.1) [15.4, 34.7] 38/132 (28.8) [21.2, 37.3]22/67 (32.8) [21.8, 45.4]16/65 (24.6) [14.8, 36.9] 49/168 (29.2) [22.4, 36.7]29/84 (34.5) [24.5, 45.7]20/84 (23.8) [15.2, 34.3] Median DOR, a mo [95% CI] c-Met OE total c-Met high c-Met int 7.2 [5.5, 11.3]9.0 [3.8, 12.0]7.2 [4.7, 11.5] 7.2 [5.5, 11.0]9.0 [3.8, 11.3]7.2 [5.3, 11.5] 7.2 [5.5, 11.0]7.2 [4.2, 12.0]7.2 [4.7, 11.5] a Per independent central review. DOR, duration of response.
TPS4202 Background: The MET proto-oncogene and its receptor tyrosine kinase gene product (c-Met protein) are involved in normal cellular functions such as cell proliferation and differentiation but can be abnormally activated and upregulated in cancer to promote tumor growth. MET gene amplification and increased c-Met protein expression are associated with poor survival outcomes in gastric cancer. The antibody-drug conjugate Temab-A (ABBV-400) is composed of the c-Met–directed antibody telisotuzumab conjugated to a potent topoisomerase 1 inhibitor. A phase 1 study (NCT05029882) investigating Temab-A monotherapy demonstrated manageable safety and encouraging efficacy in patients with previously treated, advanced GEA, with an objective response rate of 29% (12/42) and clinical benefit rate of 71% (30/42) (Strickler et al. Ann Oncol . 2024;35:1439P). This study evaluates Temab-A in combination with fluorouracil (5-FU), leucovorin/folinic acid (LV), and budigalimab (budi; a PD-1–blocking antibody). Methods: This multicenter,phase 2, open-label, randomized study (NCT06628310) will enroll ~180 adult patients with HER2-negative a/m GEA who have not received prior systemic therapy in the a/m setting, have not received a prior PD-(L)1 inhibitor, have Eastern Cooperative Oncology Group performance status 0–1, and have measurable disease per RECIST v1.1. Primary objectives of the study are to evaluate safety and tolerability, evaluate efficacy as measured by progression-free survival and objective response, and select the recommended phase 3 dose of Temab-A in combination with 5-FU, LV, and budi. Secondary objectives include assessment of dose-limiting toxicities (DLTs) in the dose-escalation stage, evaluation of pharmacokinetics, and further evaluation of efficacy measures (duration of response, disease control, and overall survival). The study consists of 2 stages: dose escalation and dose optimization. During BOIN-directed dose escalation, ~18 patients receive escalating doses of Temab-A administered once every 4 weeks (Q4W) in combination with fixed doses of 5-FU (2400 mg/m 2 Q2W), LV (400 mg/m 2 Q2W), and budi (500 mg Q4W). DLTs are assessed during the first 28-day cycle. During dose optimization, ~162 patients are randomized 1:1:1 to 1 of 2 selected doses of Temab-A in combination with 5-FU, LV, and budi or a control arm of FOLFOX + budi. Randomization is stratified by PD-L1 expression and primary tumor location. Treatment is administered until disease progression, intolerable toxicity, or other discontinuation criteria are met. Either archived formalin-fixed paraffin-embedded tissue or a fresh biopsy is required for biomarker research that will include evaluation of c-Met protein expression and MET genomic alterations. Clinical trial information: NCT06628310 .
