8500 Background: In the phase 2 KRYSTAL-7 study (NCT04613596), first-line ADA, a KRAS G12C inhibitor, plus PEMBRO demonstrated clinical activity and a manageable safety profile in pts with advanced/metastatic KRAS G12C -mutated NSCLC and PD-L1 ≥50% (Garassino et al. Ann Oncol 2023). Here we report efficacy and safety data, including the first disclosure of survival data, for pts across all PD-L1 tumor expression levels. Methods: Pts with advanced/metastatic KRAS G12C -mutated NSCLC and known PD-L1 tumor proportion score received first-line ADA (400 mg orally BID) plus PEMBRO (200 mg IV Q3W). The primary endpoint was investigator-assessed objective response rate (ORR) per RECIST v1.1. Secondary endpoints included duration of response (DOR) and progression-free survival (PFS) assessed by investigator, overall survival (OS), and safety. Results: As of August 23, 2024, 149 pts had received ADA plus PEMBRO (median OS follow-up 22.8 mo): median age was 67 years, 48% were female, and 62% had ECOG PS 1. ORR was 44.3% (95% CI 36.2–52.7); median DOR was 26.3 mo (95% CI 14.9–not estimable [NE]); median PFS was 11.0 mo (95% CI 5.8–14.0) with an 18-mo PFS rate of 37.6% (95% CI 29.0–46.1); and median OS was 18.3 mo (95% CI 14.3–NE) with an 18-mo OS rate of 51.8% (95% CI 43.0–59.8). Efficacy outcomes per PD-L1 status are shown in the Table. Treatment-related adverse events (TRAEs) of any grade (G) were reported in 94.6% of pts (G3/4 in 68.4%); three G5 TRAEs were reported (pneumonia [n=2]; pneumonitis [n=1]). The most common hepatic TRAEs (any G) were increases in alanine aminotransferase (39.6%; G3/4 in 11.4%), aspartate aminotransferase (35.6%; G3/4 in 14.1%), and alkaline phosphatase (19.5%; G3/4 in 6.7%). The discontinuation rate due to hepatic TRAEs was 2.0% for ADA, 6.7% for PEMBRO, and 0.7% for both ADA and PEMBRO. Conclusions: In pts with advanced/metastatic KRAS G12C -mutated NSCLC, first-line ADA plus PEMBRO demonstrated promising clinical efficacy and a manageable safety profile, regardless of PD-L1 status. These data represent the largest dataset evaluating a first-line KRAS G12C inhibitor plus PD-(L)1 inhibitor in this population presented to date. The phase 3 portion of KRYSTAL-7, comparing first-line ADA plus PEMBRO vs PEMBRO monotherapy in pts with KRAS G12C -mutated NSCLC and PD-L1 ≥50%, is ongoing and recruiting. Clinical trial information: NCT04613596 . PD-L1 <50%(n=95) PD-L1 ≥50%(n=54) ORR, n (%)95% CI 34 (35.8)26.2–46.3 32 (59.3)45.0–72.4 Median DOR, mo (95% CI) (n=34)18.2 (11.1–NE) (n=32)26.3 (26.3–NE) Median PFS a , mo (95% CI)18-mo rate, % (95% CI) 6.9 (3.9–12.4)29.8 (19.8–40.4) 27.7 (8.1–NE)50.7 (35.5–64.0) Median OS b , mo (95% CI)18-mo rate, % (95% CI) 15.5 (11.1–21.0)45.2 (34.3–55.6) NE (15.4–NE)62.4 (47.5–74.1) a Median PFS follow-up 17.5 mo (PD-L1 <50%) and 22.6 mo (PD-L1 ≥50%); b Median OS follow-up 21.4 mo (PD-L1 <50%) and 24.9 mo (PD-L1 ≥50%).
8541 Background: Biomarker testing is essential to optimize lung cancer (LC) care, yet uptake of testing is suboptimal due to lack of access, cost, and long turnaround times (TAT). Recent advances now require biomarker testing in early-stage LC. In 2024, the International Association for the Study of Lung Cancer (IASLC) launched a 2 nd global survey to measure improvements and barriers to implementation of testing. We compared results from North America (NA) with global results by high income (HIC) and low or middle income countries (LMIC). Methods: A multi-disciplinary committee of oncologists, pathologists, pulmonologists, epidemiologists, and advocacy partners created the survey. We used mixed methods, with focus groups and in-depth interviews informing the quantitative survey with IRB oversite. Chi-square tests were utilized to compare frequencies between NA v Other HIC (OHIC) and HIC v LMIC. Results: Of the 1677 responses globally, 1501 were from HIC and 176 from LMIC. HIC included 337 responses from NA (287 United States and 50 Canada). Nearly all NA respondents (99%) believe biomarker testing significantly impacts patient outcomes and 94% report a clear understanding of who should be tested (v 91% OHIC, p=0.09). In NA, 66% and 40% ranked biomarker testing as highly important in late- and early- stage LC, respectively (64% and 28% OHIC, p=0.68 and p<0.01). Only 45% of NA respondents were satisfied with biomarker testing conditions (v 52% OHIC, p=0.03), and 69% estimate at least half of LC patients receive biomarker testing (71% OHIC), an increase from 45% in the 2018 survey (p<0.01). We found 40% of respondents from NA sometimes or often began treatment prior to obtaining biomarker results (41% OHIC). Key barriers identified were cost (23%), time (22%), and sample quality (20%), consistent with global and OHIC trends. Mean TAT in NA was 17.1 days (SD 7.8) v 16.1 days (SD 9.0) in HIC. Insufficient tumor was the primary cause for re-biopsy in late and early-stage patients for NA (58%) and HIC (48%). Lastly, 14% of NA reported no additional training in next-generation sequencing beyond medical education (16% OHIC). Globally, conditions were worse in LMIC v HIC including those who sometimes or often begin treatment prior to obtaining biomarker results (73% v 41%, p<0.01) and those who are confident or extremely confident in the adequacy of testing at their institution (48% v 68%, p<0.01). Conclusions: Respondents from NA believe they understand the value of biomarker testing for LC and who should be tested. Testing practices have reportedly improved since 2018, yet less than half of NA respondents are satisfied with biomarker testing practices and many patients are still treated without biomarker information. Responses from NA were similar to OHIC, with some exceptions, but significant disparities were evident in LMIC. We identified key barriers that should be addressed to optimize testing practices and patient outcomes.
8585 Background: Despite advancements in third line treatments, long-term survival for advanced non-small cell lung cancer (NSCLC) remains suboptimal, with median survival follow-up of only 5.8 months. 1 Among patients treated with prior platinum chemotherapy and immune checkpoint inhibitors (ICIs), the median survival was reported to be 6.47 months 2 . Treatment options for ICI-resistant patients are limited. THIO, a telomere-targeting agent that modifies telomeres in cancer cells, demonstrates improved overall survival (OS) independent of PD-L1 expression. Methods: NCT05208944 is a phase 2, multicenter, open-label study that enrolled 79 patients with advanced NSCLC who relapsed after 1–4 prior treatments, including ICIs. In the third line therapy 22 patients treated with THIO (60, 180, or 360 mg) were evaluated for OS and their prior PD-L1 expression at the time of study enrollment (C1D1). Results: In the third line therapy 22 patients have a current median survival follow-up of 13 months which significantly surpassed the benchmark value, and in the 180 mg dose group (n=10) it reached 16.9 months compared to 5.8 months for the benchmark. 1 THIO followed by cemiplimab was generally well tolerated in this difficult-to-treat population. The response to THIO and cemiplimab, demonstrated by partial response (PR) and stable disease (SD) was independent of baseline PD-L1 status. This indicates that THIO can be effective across patients regardless of their PD-L1 status. Conclusion: THIO demonstrates clinically meaningful OS improvement in third line patients with advanced NSCLC, independent of PD-L1 status. The improved OS observed in patients treated with THIO in sequential combination with an ICI, compared to standard chemotherapy, supports its potential to expand treatment options for ICI-resistant advanced NSCLC. Clinical trial information: NCT05208944 .
AIM:In our institute, we have been testing EGFR T790M resistance mutations since 2019, which is the most common resistance mutation that develops during first-line, second- line EGFR TKI treatment of EGFR mutant lung adenocarcinomas. The importance of this study is that the identification of this mutation will allow the use of an effective third-generation TKI. In this article, we report on studies from January 2022 to August 2024, compared with our results from the 2019-2021 period. METHODS:380, predominantly blood samples from 222 patients were tested during the present period using Super- ARMS EGFR Mutation Detection Kit (AmoyDx). RESULTS:EGFR mutations were identified in 57% of all samples in the primary tumours, with a 38.3% frequency of T790M mutation. CONCLUSIONS:Our results were similar to the previous period. The number of rebiopsies was essentially unchanged compared to the 2019-2021 period, which may be the main reason why we were able to identify the mutation in a lower percentage compared to the T790M hit rate described in the literature.
