Updated OS Research Articles

NALIRIFOX versus nab-paclitaxel and gemcitabine in treatment-naïve patients with metastatic pancreatic ductal adenocarcinoma (mPDAC): Updated overall survival analysis with 29-month follow-up of NAPOLI 3.

4136 Background: NAPOLI 3 (NCT04083235, N = 770), a global, randomized, open-label phase 3 study, demonstrated that NALIRIFOX significantly improved overall survival (OS, primary endpoint) and progression-free survival compared with nab-paclitaxel and gemcitabine in patients with untreated mPDAC. Here, we report an updated analysis of OS. Methods: Eligible patients with histopathologically/cytologically confirmed untreated mPDAC were randomized (1:1) to receive liposomal irinotecan 50 mg/m2 + oxaliplatin 60 mg/m2 + leucovorin 400 mg/m2 + 5-fluorouracil 2400 mg/m2 (NALIRIFOX, n = 383) on days 1 and 15 of a 28-day cycle or nab-paclitaxel 125 mg/m2 and gemcitabine 1000 mg/m2 (Gem+NabP, n = 387) on days 1, 8 and 15 of a 28-day cycle. Randomization was stratified by ECOG performance status, geographic region and presence/absence of liver metastases. An updated OS analysis (data cutoff: 3 October 2023) was conducted. Kaplan–Meier methods were used to estimate median (95% confidence interval [CI]) OS and hazard ratios (HRs [95% CI]) were estimated using stratified Cox proportional hazard models. The difference between groups was tested using a stratified log-rank test. Results: The median follow-up for OS was 28.7 months in the NALIRIFOX arm and 29.7 months in the Gem+NabP arm. At data cutoff, 11 patients were still receiving study treatment, all of whom were in the NALIRIFOX arm. With a total of 673 OS events (NALIRIFOX, n = 328; Gem+NabP, n = 345), median OS was 11.1 months (95% CI 10.0–12.1) in the NALIRIFOX arm compared with 9.2 months (8.3–10.6) in the Gem+NabP arm (HR 0.84 [95% CI 0.72–0.98]; nominal p = 0.026). At 12 months and 18 months, survival rates were 45.6% (95% CI 40.5–50.5) and 26.6% (22.2–31.1), respectively, in the NALIRIFOX arm and 39.6% (34.7–44.5) and 20.0% (16.1–24.1), respectively, in the Gem+NabP arm. Conclusions: In this 29-month follow-up of NAPOLI 3, NALIRIFOX continued to demonstrate improved OS compared with Gem+NabP, with 11 patients still receiving the NALIRIFOX regimen. These data confirm NALIRIFOX as a new possible standard of care and reference regimen for the first-line treatment of patients with mPDAC. Clinical trial information: NCT04083235 .

Abstract PO2-04-04: Trastuzumab deruxtecan for the treatment of patients with HER2-positive breast cancer with brain and/or leptomeningeal metastases: an updated overall survival analysis using data from a multicenter retrospective study (ROSET-BM)

Abstract Background: ROSET-BM (UMIN000044995) was a multicenter, retrospective chart review study of patients (pts) who received trastuzumab deruxtecan (T-DXd) treatment for HER2-positive (HER2+) metastatic breast cancer (MBC) with brain metastases (BM) and/or leptomeningeal carcinomatosis (LMC). Primary results (data cutoff, October 31, 2021) were presented at SABCS2022 (median progression-free survival [PFS], 16.1 months; 1-year overall survival [OS] rate, 74.9%; and median follow-up duration, 11.2 months). To confirm the long-term effectiveness of T-DXd in HER2+ MBC pts with BM and/or LMC, we conducted an updated analysis using additional 1-year follow-up data. Methods: Pts who started T-DXd treatment between May 25, 2020, and April 30, 2021, were registered for ROSET-BM. For this updated OS analysis, the extended observation period ended on October 31, 2022. OS, PFS, and time to treatment failure (TTF) were evaluated. Median survival times and 95% CIs were calculated using the Kaplan–Meier method. In addition, prespecified and exploratory subgroup analyses were performed based on patient background characteristics. Univariate and multivariate Cox proportional hazards regression models were used to evaluate baseline prognostic factors for OS. Results: 104 pts from 62 institutions were included in this updated OS analysis. Median duration of follow-up was 20.4 months. Median number of prior lines of therapy was 4 (range, 1–15). Median time from first diagnosis of MBC to first administration of T-DXd was 37.5 months. Median time from first diagnosis of BM to first administration of T-DXd was 18.9 months. The prevalence of active BM, stable BM, LMC, and unclassified (image not evaluated) was 64.4% (n=67), 11.5% (n=12), 18.3% (n=19), and 5.8% (n=6), respectively. Median OS was not reached (NR) among all pts (1-year OS rate, 74.8%; 2-year OS rate, 56.0%). Subgroup analyses showed that median OS in pts with active BM was 27.0 months (95% CI, 16.4 to NR) and that median OS was NR in pts with stable BM or LMC (2-year OS rate for pts with stable BM, 71.6%; 2-year OS rate for pts with LMC, 61.6%). The results of univariate and multivariate analyses for OS showed no relevant baseline prognostic factors. Among all pts, median PFS was 14.6 months (95% CI, 10.6–20.8). Subgroup analyses showed that in pts with active BM, stable BM, and LMC, median PFS was 13.2 months (95% CI, 10.0–20.3), NR (95% CI, 5.3 to NR), and 17.5 months (95% CI, 8.3–22.1), respectively. Among all pts, median TTF was 9.3 months (95% CI, 6.3–11.8). The most common event and adverse event leading to discontinuation of T-DXd was progressive disease (37 pts, 35.6%) and interstitial lung disease (ILD; 24 pts, 23.1%), respectively. Median time to onset of an ILD event was 5.3 months (range, 0.7–20.0). ILD was grade 1 in 14 pts (13.5%), grade 2 in 3 pts (2.9%), grade 3 in 5 pts (4.8%), grade 4 in 2 pts (1.9%), and grade 5 in 0 pts. The Table summarizes the primary and updated results of ROSET-BM. Conclusion: The updated OS results of this retrospective chart review show that T-DXd has promising effectiveness in HER2+ MBC pts with long-term and heavily pretreated BM and LMC. This study was funded by Daiichi Sankyo Co., Ltd. Primary and updated results from the ROSET-BM study The updated results show that T-DXd has promising effectiveness in HER2+ MBC pts with long-term and heavily pretreated BM and LMC. Citation Format: Takashi Yamanaka, Naoki Niikura, Takahiro Nakayama, Mitsugu Yamamoto, Kazuo Matsuura, Kenichi Inoue, Sachiko Takahara, Hironori Nomura, Shosuke Kita, Miki Yamaguchi, Tomoyuki Aruga, Nobuhiro Shibata, Akihiko Shimomura, Yuri Ozaki, Shuji Sakai, Daisuke Takiguchi, Takehiko Takata, Armin Bastanfard, Kazuhito Shiosakai, Junji Tsurutani. Trastuzumab deruxtecan for the treatment of patients with HER2-positive breast cancer with brain and/or leptomeningeal metastases: an updated overall survival analysis using data from a multicenter retrospective study (ROSET-BM) [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-04-04.

Evolving Evidence-Based Value Assessment of One-Time Therapies: Tisagenlecleucel as a Case Study.

Economic evaluation of one-time therapies during reimbursement decision-making is challenging due to uncertain long-term outcomes. The availability of 5-year outcome data from the ELIANA trial and real-world evidence of tisagenlecleucel, the first chimeric antigen receptor T-cell (CAR-T) therapy, presents an opportunity to re-evaluate the predictions of prior cost-effectiveness analyses (CEAs). To conduct a systematic literature review (SLR) of prior CEAs of tisagenlecleucel for pediatric/young adult relapsed or refractory acute lymphoblastic leukemia (r/r ALL) and evaluate the impact of recently available 5-year efficacy data from ELIANA and advances in CAR-T manufacturing in an updated CEA model. OVID MEDLINE/Embase and health technology assessment (HTA) databases were searched for full-text economic evaluations in English reporting cost-effectiveness results for tisagenlecleucel for r/r ALL. Evaluations with publicly reported incremental cost-effectiveness ratios (ICERs) were included in the SLR. Study screening and data abstraction were conducted following PRISMA guidelines. Data extracted included the country/currency, perspective, clinical trial evidence, model structures, long-term efficacy extrapolation approaches (i.e., overall survival [OS]), time horizon, discount rates, and outcomes (i.e., life years [LY], quality-adjusted LY [QALY], and ICERs). The CEA model reported in Wakase et al. was updated using 5-year OS data from ELIANA and the CAR-T infusion rate informed by real-world practice. Sixteen records corresponding to 15 unique studies were included in the SLR (11 publications and 5 HTA reports); all were conducted from the health care system perspective of the respective countries. Most studies found tisagenlecleucel to be cost effective, but all studies' projected 3- and 5-year OS rates for tisagenlecleucel were lower than the observed 3- and 5-year rates, respectively, derived from 5-year ELIANA data. When applying updated OS projections from the most recent ELIANA data cut and higher infusion rates of 92.5% (per the real-world infusion rate)-96.0% (per the manufacturer success rate) to theCEA of Wakase et al., the associated QALYs for tisagenlecleucel increased from 11.6 to 14.6-15.0, andLYs increased from 13.3 to 17.0-17.5. Accordingly, the ICERs for tisagenlecleucel decreased from ¥2,035,071 to ¥1,787,988-¥1,789,048 versus blinatumomab and from ¥2,644,702 to ¥2,257,837-¥2,275,181 versus clofarabine combination therapy in the updated CEA model. Projections at launch of the likely cost effectiveness of tisagenlecleucel appear to have underestimated its ultimate economic value given more recent trial and real-world data. To balance uncertainty in initial valuation with the need to provide access to novel oncology therapies, payers can consider flexible reimbursement policies alongside ongoing assessments as new data emerge.

Nivolumab (Nivo) plus ipilimumab (Ipi) 6-month treatment versus continuation in patients with advanced non-small-cell-lung cancer (aNSCLC): 3-year results of the IFCT-1701 DICIPLE phase 3 trial.

9068 Background: 1st-line immunotherapy (io) is a standard treatment for patients (pts) with advanced NSCLC devoid of targetable mutation. Classical 2-year io duration does not rely on indubitable evidence. We aimed to assess whether 6-month nivo/ipi was equivalent to continuation until progression or unacceptable toxicity in pts with disease control (DC). Methods: In this multicenter non-inferiority randomized phase 3 trial, eligible treatment-naive pts, age>18, PS 0-1, had stage IV NSCLC and measurable disease. They received Nivo 3 mg/kg q2w plus Ipi 1 mg/kg q6w, until progression or unacceptable toxicity for a maximum of 6-month induction treatment. At 6 months, pts with DC and no severe TRAEs were randomized (1:1) into io continuation (arm A), and observation (arm B). At progression, arm A pts received an investigator's choice 2nd line platinum-based chemo, while arm B pts resumed double io. Primary endpoint was progression-free survival (PFS). 450 pts x 2 were to be randomized, to achieve 80% power, with 0.025 one-sided a error. Observing that European filing for the io combo was not submitted, the trial's steering committee recommended to stop the accrual on Jan. 2021. Results: From May. 2018 to Jan. 2021, 265 pts (70.6% male, 62.7yr median age, 59% stage IVB, 22.3% SCC, 9.9% PDL1≥50%, 12.2% PDL1<1%) were accrued. 138 (72.6%) pts had disease progression before 6 months, 11 died (5.8%), 30 (15.8%) experienced TRAEs contra-indicating continuation, 11 (5.8%) were deemed ineligible for randomization. 71 pts with DC were randomized. With a median follow-up from randomization of 29.9 months, median PFS was 20.5 (7.4-36.7) months in arm A, 35.2 (21.4-NR) in arm B. 12-month PFS was 55.6% (38.0-69.9) and 81.2% (62.9-91.1), respectively (p=0.08). Adj.HR (arm B vs. arm A) was 0.66, 95%CI (0.28-1.31), p=0.23. OS data, yet immature, did not show any significant difference between both arms (adj.HR arm B vs. A: 0.54 95%CI (0.20-1.49), p=0.23). From randomization, 28.6% G3-5 TRAEs in arm A were observed vs. 2.9% in arm B (p=0.005). Conclusions: The 6-month i.o. interruption for NSCLC patients with DC did not yield significant PFS or OS differences in this prematurely halted trial. Updated OS with a 3-year follow-up, quality of life and biomarker data, will be presented at the meeting. Clinical trial information: NCT03469960 .

Pertuzumab retreatment in patients with HER2-positive locally advanced/metastatic breast cancer: Overall survival results of a phase III randomized trial (JBCRG-M05: PRECIOUS).

1015 Background: We previously reported that pertuzumab (P) retreatment in combination with trastuzumab (T) + chemotherapy based on physician’s choice (C) (PTC) significantly improved investigator-assessed progression-free survival (PFS) compared with T + C (TC) in patients with HER2-positive locally advanced/metastatic breast cancer (LA/MBC) previously treated with P-containing regimens in the phase III PRECIOUS study. Here we report updated OS at the median follow-up of 27.4 mo. Methods: Patients previously treated with P-containing regimens as 1st/2nd-line treatment for LA/MBC were randomly assigned 1:1 to two groups, PTC group and TC group, stratified by estrogen receptor (ER) status, previous treatment duration of P, number of previous chemotherapy regimens, and presence or absence of visceral metastasis. The primary endpoint was investigator-assessed PFS. The key secondary endpoints included OS, independent reviewer assessed PFS and safety. Superiority of PTC to TC will be tested using a log-rank test and a one-sided P-value of less than 0.05 will be considered an indicator of superiority. The distribution of OS will be estimated using the Kaplan-Meier method. In addition, the hazard ratio and one-sided 95% CI of the therapeutic effect between the groups will be calculated using the Cox proportional hazard model. Results: Of the 219pts enrolled, 217 (108 PTC, 109 TC) were included in the intent-to-treat analysis. At the data cutoff (Dec 31, 2021), OS and PFS events were 138 (63.6%) and 190 (87.6%), respectively. Updated median OS was significantly longer in the PTC group (median OS 36.2 vs. 26.5 mo.; HR = 0.73 [one side 95%CI upper limit, 0.97]; log-rank test p = 0.0323). In a prespecified subgroup analysis for OS including ER, visceral metastases, number of previous chemotherapy regimen was broadly constant without disease-free interval. Updated median investigator-assessed PFS (5.5 vs. 4.2 mo.; HR = 0.81 [one side 95%CI upper limit, 1.03]; stratified log-rank test p = 0.019) were also significantly better in the PTC group. Median PFS by independent review did not show the difference between two groups (4.4 vs. 4.4 mo.; HR = 1.03 [one side 95%CI upper limit, 1.36]; log-rank test p = 0.561). The serious adverse event rate did not differ between the groups (19.0% vs. 23.1%). There were no new safety signals in the two groups. Conclusions: Retreatment of P in combination with TC demonstrated significantly improved OS compared to TC. HER2 dual blockade with PT can contribute to improve survival in patients previously treated with P-containing regimens as 1st/2nd-line treatment for LA/MBC. Clinical trial information: NCT02514681 .

Updated OS of patients with AL amyloidosis after CAEL-101.

8026 Background: Morbidity and mortality remain high in immunoglobulin light chain (AL) amyloidosis due to organ involvement despite hematologic remission. Few anti-amyloid fibril therapies for AL amyloidosis exist. We previously published the results of the phase 1a/1b study of CAEL-101 in AL amyloidosis showing significant improvement in organ response rates.1 We report long-term outcomes. Methods: Patients enrolled in NCT02245867 with relapsed/refractory AL amyloidosis received in phase 1a, a one-time dose-finding CAEL-101 infusion and in phase 1b, 4 weekly CAEL-101 infusions with preplanned dose escalation. Patients were evaluated for organ response for 12 weeks after last infusion. We extracted clinical, laboratory, and pathology data regarding clinical course beyond 12 weeks after last treatment. We performed a review of all AL amyloidosis patients at our center not treated with CAEL-101 1/01/2012-12/30/19 as clinical comparisons. Results: 22 patients were enrolled in CAEL-101. 5 patients were treated in both phase 1a and phase 1b. With median follow-up of 81.3 months (IQR 60.4-87.7), long term follow-up data are available for 19/22 patients. 5 patients died during long term follow-up: 3 from progressive AL amyloidosis; 1 from organ transplantation complication; and 1 from venous thromboembolism sequelae. Among patients with organ data available, 10/17 had hematologic progression and received next line therapy. 5/17 patients had organ progression. All patients with organ PD had previous/concomitant hematologic PD. Median OS was not reached; median organ PFS was 93.3 months (38.9-NR). No delayed adverse events occurred. Comparison with historical control groups revealed trends toward improved OS: HR 0.42 (0.09-1.81 p=0.23) in all comers AL amyloid controls, and HR 0.20 (0.03-1.16 p=0.07) in cardiac controls. Kaplan-Meier analysis and Cox regression were performed. Conclusions: Patients with relapsed/refractory AL amyloidosis who received a low cumulative amount of the novel anti-amyloid CAEL-101 in a phase 1a/1b study had lengthy overall and progression-free survival compared to historical controls. Patterns of organ progression after initial response may reflect intrinsic differences in organ vulnerability. The CAEL101-301 and CAEL101-302 phase 3 clinical trials are underway to confirm these findings. Reference: 1. Edwards CV, Rao N, Bhutani D, et al: Phase 1a/b study of monoclonal antibody CAEL-101 (11-1F4) in patients with AL amyloidosis. Blood 138:2632-2641, 2021. [Table: see text]

Abstract CT200: Updated PFS & OS from the phase Ib study of TQB2450 alone/with Anlotinib in previously treated advanced non-small cell lung cancer

Abstract Background: At the interim analysis (data cutoff Oct 14, 2021) of this study (NCT03910127), TQB2450 plus anlotinb group significantly improved mPFS versus TQB2450 alone in chemotherapy treated patients with advanced NSCLC without driver gene alterations (6.9 months vs 2.7 months). We report an updated PFS, OS and safety results for this study. Method: This is a multicenter, randomized, double-blind, phase Ib study. Adult patients with histologically or cytologically-confirmed stage IIIB or IV NSCLC who had wild-type EGFR/ALK and at least one line of prior systemic therapy or being intolerable of chemotherapy were randomized 1:1:1 to receive TQB2450 1200 mg plus placebo, or anlotinib 10 or 12 mg. The primary end point was PFS and secondary endpoints included safety and OS. Results: Between July. 2019 and March. 2021, 101 pts were enrolled. 33 patients were randomly assigned to TQB2450 plus placebo and 68 patients to TQB2450 plus anlotinib. As of 19 September 2022, The median follow-up was 26.3 months. The median PFS (7.3 months, 95% CI 5.3-11.0) for TQB2450 plus anlotinib was significantly longer than that for TQB2450 plus placebo group (2.8 months, 95% CI 1.4-4.7) (HR 0.39, 95% CI 0.23-0.64; P=0.0001) (Table). In patients with PD-L1 ≥ 1%, the mPFS was 17.9 months (95% CI 5.8-31.1) in TQB2450 plus anlotinib 12 mg, which was numerically higher than that in TQB2450 plus anlotinib 10 mg. The median OS of patients with PD-L1 ≥ 1% for TQB2450 plus anlotinib 12 mg was numerically higher than that in TQB2450 plus anlotinib 10 mg (32.2 months vs 21.8 months). Grade 3 or higher TRAEs occurred in 50.0% of the patients in TQB2450 plus anlotinb and in 12.1% of those in TQB2450 plus placebo. Conclusions: In this updated analysis with longer follow-up, TQB2450 combined with anlotinib continues to demonstrate overall efficacy and manageable safety profiles in chemotherapy treated patients with advanced NSCLC without driver gene mutations. TQB2450 TQB2450+Anlotinib 10mg TQB2450+Anlotinib 12mg TQB2450+Anlotinib mPFS n 33 34 34 68 Censor, n (%) 7 (21.2) 9 (26.5) 8 (23.5) 17 (25.0) Median (95%CI) 2.8 (1.4-4.7) 7.0 (4.5-14.5) 8.7 (4.1-11.4) 7.3 (5.3-11.0) HR (95%CI) 0.37 (0.21-0.66) 0.40 (0.22-0.70) 0.39 (0.23-0.64) P value 0.0006 0.0001 mPFS (PD-L1≥1%) n 19 19 19 38 Censor, n (%) 3 (15.8) 6 (31.6) 7 (36.8) 13 (34.2) Median (95%CI) 2.1 (1.3-7.2) 7.0 (2.1-19.4) 17.9 (5.8-31.1) 8.6 (5.3-22.8) HR (95%CI) 0.35 (0.16-0.77) 0.29 (0.13-0.64) 0.32 (0.16-0.63) P value 0.0023 0.0006 mOS n 33 34 34 68 Censor, n (%) 12 (36.4) 14 (41.2) 12 (35.3) 26 (38.2) Median (95%CI) 15.3 (6.6-20.5) 20.6 (8.6-25.8) 14.7 (10.0-32.2) 17.9 (10.5-23.2) HR (95%CI) 0.78 (0.42-1.44) 0.84 (0.46-1.53) 0.81 (0.48-1.37) P value 0.7157 0.4329 mOS (PD-L1≥1%) n 19 19 19 38 Censor, n (%) 5 (26.3) 7 (36.8) 8 (42.1) 15 (39.5) Median (95%CI) 15.7 (7.8-21.0) 21.8 (7.1-NR) 32.2 (14.2-33.6) 21.8 (14.2-33.6) HR (95%CI) 0.72 (0.33-1.58) 0.63 (0.28-1.40) 0.67 (0.34-1.32) P value 0.4900 0.2479 Citation Format: Baohui Han, Kai Li, Qiming Wang, Ying Cheng, Lei Yang, Yueming Li. Updated PFS & OS from the phase Ib study of TQB2450 alone/with Anlotinib in previously treated advanced non-small cell lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr CT200.

Gantt chart for updated OS and PFS after cancer targeted therapy

Gantt chart for updated OS and PFS after cancer targeted therapy

Waveline-001: Updated Results from a Phase 1 Dose Escalation and Cohort Expansion Study of Zilovertamab Vedotin (MK-2140) in Non-Hodgkin Lymphoma

Background: Zilovertamab vedotin (ZV) is a receptor tyrosine kinase-like orphan receptor 1 (ROR1) targeting antibody-drug conjugate comprising zilovertamab, a proteolytically cleavable linker, and the antimicrotubule agent monomethyl auristatin E. ROR1 is a transmembrane protein absent in mature tissues but highly expressed in certain hematologic malignancies, making it an attractive therapeutic target. Safety and efficacy of ZV are being investigated in the phase 1 WAVELINE-001 study (NCT03833180), which is a dose escalation and cohort expansion analysis in patients (pts) with relapsed and/or refractory (R/R) hematologic malignancies. Initial results showed ZV had a tolerable safety profile and promising antitumor activity in R/R non-Hodgkin lymphoma (NHL; Wang M, et al. NEJM Evid. 2021;1[1]). Updated results, including PFS and OS for mantle cell lymphoma (MCL), diffuse large B-cell lymphoma (DLBCL), and Richter transformation (RT), are presented. Methods: Eligible pts aged ≥18 years of age, with a histological diagnosis of MCL, DLBCL, or RT; had ECOG PS 0-2; and progression during or relapsed after prior systemic therapy, were included. WAVELINE-001 included 3 dosing schedules. Data from Schedule 1 are presented; Schedules 2 and 3 are ongoing. In Schedule 1, pts received ZV IV at a starting dose of 0.5 mg/kg on day 1 Q3W, increasing to 2.5 mg/kg using an accelerated plus 3 + 3 dose escalation design. Primary end point was determination of the maximum tolerated dose and/or recommended dosing regimen (RDR). Secondary end points included safety, ORR, DOR, PFS, and OS. Results: A total of 54 pts were enrolled in Schedule 1, of which 30 pts were treated at the established RDR of 2.5 mg/kg. At data cutoff (May 18, 2022), median follow-up was 15.3 months (range, 0.5-37.8). Median age was 70.0 yrs, 57% of pts were male, 48% had an ECOG PS of 0, 65% had received ≥3 prior therapies, 80% had NHL (FL, n=3; DLBCL, n=15; MCL, n=17; MZL, n=1; RT, n=7), and 20% had other disease (AML, n=3; CLL/SLL, n=7; mixed histology, n=1). MCL pts had received a median (range) of 4 (1-9) prior lines of therapy. All MCL pts received prior BTKi therapy, and none had prior CAR-T or CAR-NK therapy. 59% of MCL pts were Ann Arbor stage IV. DLBCL pts received a median (range) of 4 (1-7) prior lines of therapy, 67% of pts had received prior CAR-T or CAR-NK therapy; 47% of pts were GCB, and 33% were ABC subtype. Five pts (71%) with RT had the DLBCL subtype. No pts with RT received autologous stem cell transplant and received a median (range) of 3 (1-10) prior therapies. Any-cause adverse events (AEs) occurred in 52 (96%) pts. Any-grade treatment-related AEs (TRAEs) occurred in 40 pts (74%); most common (≥20%) were peripheral neuropathy (46%), neutrophil count decreased (35%), fatigue (35%), nausea (28%), and diarrhea (20%). Decreases in hemoglobin and platelet count occurred in 13% and 11% of pts, respectively. Grade 3-4 TRAEs occurred in 28 pts (52%), most commonly neutrophil count decreased (33%), platelet count decreased (11%), and peripheral neuropathy (7%). AEs of special interest regardless of causality occurred in 76% of pts; most common were hematopoietic cytopenia (56%) and peripheral neuropathy (48%). For pts experiencing peripheral neuropathy, most cases were grade 1/2 (41%); 7% were grade 3. Median (range) time to onset of first peripheral neuropathy was 49 (1-162) days. No incidences of tumor lysis syndrome or infusion reactions occurred and no grade 5 TRAEs occurred. AEs led to ZV discontinuation in 12 pts (22%) and interruption or reduction in 24 (44%). ORR was 33% (5/15; 95% CI, 12-62; 3 CR/2 PR) in DLBCL, 53% (9/17; 95% CI, 28-77; 2 CR/7 PR) in MCL, and 57% (4/7; 95% CI, 18-90; 1 CR/3 PR) in RT. No responses were seen among the other indications treated. Median DOR (range) was 4.6 months (2.9-21.5) for DLBCL, 10.0 (0-20.3) for MCL, and 2.8 (0-2.8) for RT. Median PFS (95% CI) was 3.9 months (0.5-7.0) for DLBCL, 11.4 (4.0-NE) for MCL, and 4.7 (0.7-NE) for RT. Median OS (95% CI) was 9.1 months (1.0-NE) for DLBCL, 18.0 (7.1-NE) for MCL, and 24.0 (2.7-NE) for RT. Among 12 pts with NHL (10 DLBCL and 2 RT) who had undergone prior CAR-T/CAR-NK therapy, ORR was 33% (4/12; 95% CI, 10-65). Conclusions: Updated results from WAVELINE-001 support prior analyses showing ZV had a tolerable safety profile and promising response rates, and favorable PFS and OS among heavily pre-treated pts with DLBCL, MCL, and RT, including pts who had received prior CAR-T/CAR-NK therapy.

361P 8-year long term survival status in a phase III randomized study in EGFR mutated advanced lung cancer patients in the first-line

This was phase 3 randomized study comparing Gefitinib with pemetrexed with carboplatin in EGFR mutated advanced lung cancer in the first line. The initial interim analysis had proven the superiority of gefitinib over chemotherapy in prolonging the progression free survival (PFS) this group of patients. Gefitinib also had a more favorable safety profile with different associated toxicities. Here we report the updated OS analysis of this study.

Update of a prognostic survival model in head and neck squamous cell carcinoma patients treated with immune checkpoint inhibitors using an expansion cohort

BackgroundImmune checkpoint inhibitors (ICI) treatment in recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) offers new therapeutic venues. We have previously developed a predictive survival model in this patient population based on clinical parameters, and the purpose of this study was to expand the study cohort and internally validate the model.MethodsA single institutional retrospective analysis of R/M HNSCC patients treated with ICI. Clinical parameters collected included p-16 status, hemoglobin (Hb), albumin (Alb), lactate dehydrogenase (LDH), neutrophil, lymphocyte and platelet counts. Cox proportional hazard regression was used to assess the impact of patient characteristics and clinical variables on survival. A nomogram was created using the rms package to generate individualized survival prediction.Results201 patients were included, 47 females (23%), 154 males (77%). Median age was 61 years (IQR: 55-68). P-16 negative (66%). Median OS was 12 months (95% CI: 9.4, 14.9). Updated OS model included age, sex, absolute neutrophil count, absolute lymphocyte count, albumin, hemoglobin, LDH, and p-16 status. We stratified patients into three risk groups based on this model at the 0.33 and 0.66 quantiles. Median OS in the optimal risk group reached 23.7 months (CI: 18.5, NR), 13.8 months (CI: 11.1, 20.3) in the average risk group, and 2.3 months (CI: 1.7, 4.4) in the high-risk group. Following internal validation, the discriminatory power of the model reached a c-index of 0.72 and calibration slope of 0.79.ConclusionsOur updated nomogram could assist in the precise selection of patients for which ICI could be beneficial and cost-effective.

Tremelimumab (day 1 only) and durvalumab in combination with transarterial chemoemobilization (TACE) in patients with hepatocellular carcinoma (HCC).

e16175 Background: TACE induces a peripheral anti-tumor immune response, which may be amplified by immune checkpoint inhibitors (ICI). Combining TACE with dual ICI therapy has been shown to be safe and feasible. Recent data has suggested that Day-1 only anti-CTLA4 dosing, at a higher level of 300mg, could lead to a stronger immune response, and drive a greater expansion than lower dose regimens, whilst maintaining a tolerable safety profile. This novel schedule has not previously been combined with TACE. Methods: Patients with HCC (Childs Pugh A/B7, Barcelona clinic liver cancer stage B/C; ECOG 0/1; sorafenib-naive or experienced) were enrolled in a pilot study of tremelimumab at 2 dose levels (DL1: 75mg IV q4-weekly x 4 and DL2: 300mg IV D1 only) in combination with durvalumab (1500mg IV q-28d) and TACE (D36 +/- 96 hours) until progression of disease (per irRECIST) or off-study criteria. Peripheral immune monitoring was performed and tumor biopsies were obtained at time of TACE. Results: 13 patients enrolled on study; N = 3 at DL1 and N = 10 at DL2. M:F 10:3. Median age 70 (65-74). BCLC B/C 4/9. Extrahepatic disease 6/7. Aetiology: NASH (N = 3), alcohol-related disease (N = 1), HCV (N = 2), hemochromatosis (N = 1), unknown (N = 6). 1 pt discontinued due to G3 colitis. All patients evaluable for response with 2/10 pts on DL2 experiencing PR (at 8 weeks) and overall 7/13 SD and 1/13 PD as best response. Updated PFS and OS data to be presented. Conclusions: Tremelimumab (Day 1 only) and Durvalumab in combination with TACE is safe and feasible in patients with HCC. Follow-up is ongoing and full safety and efficacy data will be presented. Clinical trial information: 2019-002767-98.

Five-Year Survival Outcomes From the PACIFIC Trial: Durvalumab After Chemoradiotherapy in Stage III Non-Small-Cell Lung Cancer.

PURPOSEThe phase III PACIFIC trial compared durvalumab with placebo in patients with unresectable, stage III non–small-cell lung cancer and no disease progression after concurrent chemoradiotherapy. Consolidation durvalumab was associated with significant improvements in the primary end points of overall survival (OS; stratified hazard ratio [HR], 0.68; 95% CI, 0.53 to 0.87; P = .00251) and progression-free survival (PFS [blinded independent central review; RECIST v1.1]; stratified HR, 0.52; 95% CI, 0.42 to 0.65; P < .0001), with manageable safety. We report updated, exploratory analyses of survival, approximately 5 years after the last patient was randomly assigned.METHODSPatients with WHO performance status 0 or 1 (any tumor programmed cell death-ligand 1 status) were randomly assigned (2:1) to durvalumab (10 mg/kg intravenously; administered once every 2 weeks for 12 months) or placebo, stratified by age, sex, and smoking history. Time-to-event end point analyses were performed using stratified log-rank tests. Medians and landmark survival rates were estimated using the Kaplan-Meier method.RESULTSSeven hundred and nine of 713 randomly assigned patients received durvalumab (473 of 476) or placebo (236 of 237). As of January 11, 2021 (median follow-up, 34.2 months [all patients]; 61.6 months [censored patients]), updated OS (stratified HR, 0.72; 95% CI, 0.59 to 0.89; median, 47.5 v 29.1 months) and PFS (stratified HR, 0.55; 95% CI, 0.45 to 0.68; median, 16.9 v 5.6 months) remained consistent with the primary analyses. Estimated 5-year rates (95% CI) for durvalumab and placebo were 42.9% (38.2 to 47.4) versus 33.4% (27.3 to 39.6) for OS and 33.1% (28.0 to 38.2) versus 19.0% (13.6 to 25.2) for PFS.CONCLUSIONThese updated analyses demonstrate robust and sustained OS and durable PFS benefit with durvalumab after chemoradiotherapy. An estimated 42.9% of patients randomly assigned to durvalumab remain alive at 5 years and 33.1% of patients randomly assigned to durvalumab remain alive and free of disease progression, establishing a new benchmark for standard of care in this setting.

Tremelimumab (day 1 only) and durvalumab in combination with transarterial chemoemobilization (TACE) in patients with hepatocellular carcinoma (HCC).

451 Background: TACE induces a peripheral anti-tumor immune response, which may be amplified by immune checkpoint inhibitors (ICI). Combining TACE with dual ICI therapy has been shown to be safe and feasible. Recent data has suggested that Day 1-only anti-CTLA4 dosing could potentially lead to a stronger immune response with a tolerable safety profile though this novel schedule has not previously been combined with TACE. Methods: Patients with HCC (Childs Pugh A/B7, Barcelona clinic liver cancer stage B/C; ECOG 0/1; sorafenib-naive or experienced) were enrolled in a pilot study of tremelimumab at 2 dose levels (DL1: 75mg IV q4-weekly x 4 and DL2: 300mg IV D1 only) in combination with durvalumab (1500mg IV q-28d) and TACE (D36 +/- 96 hours) until progression of disease (per irRECIST) or off-study criteria. Peripheral immune monitoring was performed and tumor biopsies were obtained at time of TACE. Results: 13 patients enrolled on study; N = 3 at DL1 and N = 10 at DL2. M:F 10:3. Median age 70 (65-74). BCLC B/C 4/9. Extrahepatic disease 6/7. Aetiology: NASH (N = 3), alcohol-related disease (N = 1), HCV (N = 2), hemochromatosis (N = 1), unknown (N = 6). 1 patient discontinued due to G3 colitis. All patients evaluable for response with 2/10 patients on DL2 experiencing PR (at 8 weeks) and overall 8/13 SD and 3/13 PD as best response. Updated PFS and OS data to be presented. Conclusions: Tremelimumab (Day 1 only) and Durvalumab in combination with TACE is safe and feasible in patients with HCC. Follow-up is ongoing and full safety and efficacy data will be presented. Clinical trial information: 2019-002767-98.

LBA2 Updated analysis and patient-reported outcomes (PROs) from CITYSCAPE: A randomised, double-blind, phase II study of the anti-TIGIT antibody tiragolumab + atezolizumab (TA) versus placebo + atezolizumab (PA) as first-line treatment for PD-L1+ NSCLC

LBA2 Updated analysis and patient-reported outcomes (PROs) from CITYSCAPE: A randomised, double-blind, phase II study of the anti-TIGIT antibody tiragolumab + atezolizumab (TA) versus placebo + atezolizumab (PA) as first-line treatment for PD-L1+ NSCLC

Phase 2 Suzhou MM02 Study: Chidamide with VRD Versus VRD in Newly Diagnosed High Risk Transplant Eligible Multiple Myeloma Patients

BackgroundBortezomib with lenalidomide and dexamethasone (VRd) is a standard regimen for the induction treatment of multiple myeloma (MM) transplant eligible and ineligible patients. Deregulation of histone acetylation has been recognized to serve a critical role in the pathogenesis of MM, which histone deacetylase (HDACs) are overexpressed in plasma cells derived from patients with MM. Therefore, HDACs may promise targets for MM therapy, and panobinostat was approved by FDA for the treatment of relapsed/refractory MM in 2015. Chidamide, a novel oral benzamide type HDAC inhibitor independently developed and approved as anticancer drugs in China, selectively suppresses the activity of class I HDACs. Our studies have shown that chidamide can enhance cytotoxic effect of bortezomib or lenalidomide on MM cells in vitro, which suggested a synergistic combination of chidamide with bortezomib or lenalidomide at low dose. In ASH 2019 we reported Phase 1 Suzhou MM02 study in which chidamide at 4 dose levels (15mg/20mg/25mg/30mg d 0,3,7,10) were administered to 12 patients with VRd for 4-cycle induction therapy. No DLT in Chi-VRd group were observed. This phase 2 trial was designed to further assess the safety and efficacy of Chi-VRd versus VRd for induction treatment in patients with newly diagnosed high risk MM before autologous transplantation (NCT 04025450).MethodsIn this study, we enrolled patients from the First Affiliated Hospital of Soochow University and Soochow Hopes Hematology Hospital with newly diagnosed high-risk multiple myeloma who were aged 18 years or older and eligible for autologous stem-cell transplant (ASCT) according to International Myeloma Working Group diagnostic criteria. All the patients were randomly assigned to Chi-VRd and VRd group. Chi-VRd group patients received Chidamide 20mg orally on days -1,2,6 and 9 in combination with VRd (bortezomib 1.3mg/m2 subcutaneously on days 1,4,8,11; lenalidomide 25mg orally on days 1-14; dexamethasone 20mg iv or orally on days 1,2,4,5,8,9,11,12) for 4 cycles. VRd group patients received VRd (bortezomib 1.3mg/m2 subcutaneously on days 1,4,8,11; lenalidomide 25mg orally on days 1-14; dexamethasone 20mg iv or orally on days 1,2,4,5,8,9,11,12) for 4 cycles.All the patients proceed with ASCT after four cycles or continue VRd therapy for up to eight cycles, followed by maintenance therapy for up to 2 years. Primary efficacy endpoints were overall response rate (ORR), rate of very good partial response (VGPR) or better and rate of complete response (CR) for Chi-VRd and VRd. Safety data described rates of adverse events.ResultsBetween Mar 16, 2020, and Jul 22, 2021, 40 patients were enrolled and randomly assigned to either the VRd regimen (n=20) or the Chi-VRd regimen (n=20). In the Chi-VRd group, 1 patient was discharged due to severe tumor lysis syndrome, and another 1 patient was discharged from sick sinus syndrome (considering lenalidomide related). By the deadline for submission, 18 patients in the VRd group and 11 patients in the Chi-VRd group had completed induction chemotherapy. The total adverse events were listed in the table below. The main treatment-related adverse events were hematological toxicity, hepatotoxicity, constipation, and peripheral neuropathy. ORR was 90.9% (10/11) for Chi-VRd and was 100% for VRd. Response of VGPR or better was 81.8% (9/11) for Chi-VRd and was 83.3% (15/18) for VRd. And rate of CR was 63.6%(7/11) for Chi-VRd and was 44.4%(8/18) for VRd.ConclusionThe Chi-VRd group had more adverse events of thrombocytopenia, peripheral neuropathy and pulmonary. No treatment-related death was observed in two groups. Patients received Chi-VRd get more CR rate. Updated PFS and OS with comparison between VRd and Chi-VRd will be presented at the following study. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

279P Trastuzumab deruxtecan (T-DXd) in patients with HER2-positive metastatic breast cancer (MBC): Updated survival results from a phase II trial (DESTINY-Breast01)

T-DXd is an antibody–drug conjugate comprising a HER2 antibody, a tetrapeptide-based cleavable linker, and a topoisomerase I inhibitor payload. DESTINY-Breast01 (NCT03248492) is an open-label, international, multicenter, phase 2 study of T-DXd in patients with HER2-positive MBC; it supported regulatory approval globally. Data from prior data cutoffs (primary: August 1, 2019; initial update: June 8, 2020) showed that patients receiving T-DXd had durable responses. Confirmed overall response rate (ORR) was 61.4%, duration of response (DOR) was 20.8 months, median progression-free survival (mPFS) was 19.4 months, and median overall survival (mOS) was 24.6 months at the initial update (June 8, 2020; Modi S, SABCS 2020). Safety results were also consistent with previously reported data on T-DXd. Here we report updated OS results. Patients with MBC that progressed on or after T-DM1 were included in the study. Of the 253 patients who enrolled, 184 received T-DXd 5.4 mg/kg (primary analysis set). The primary endpoint was ORR, and additional endpoints included DOR, PFS, and OS. A total of 184 patients were assessed with ages ranging from 20.2 to 83.1 years and the number of prior lines of therapy ranging from 0 to 16. At this latest data cutoff (January 15, 2021), median duration of OS follow-up was 29.2 months (95% CI, 28.6-30.0 months). With greater maturity, the updated mOS was 28.4 months (95% CI, 24.6-37.2 months), with 91 (49.5%) OS events. Estimated OS rate was 75% (95% CI, 67%-80%) at 18 months and 58% (95% CI, 51%-65%) at 24 months. Updated results for ORR, mPFS, and mDOR will be presented, along with results of additional ongoing analyses. With increased duration of survival follow-up, the prolonged estimated mOS and high landmark survival at the 18- and 24-month landmarks indicate a significant and sustained benefit. These updated results continue to demonstrate the survival benefit of T-DXd in heavily previously treated patients with HER2-positive MBC (median prior lines of treatments, 6). The efficacy and safety of T-DXd is currently undergoing further investigation in randomized controlled clinical trials.

LBA-1 Phase 3 APACT trial of adjuvant nab-paclitaxel plus gemcitabine (nab-P + Gem) vs gemcitabine (Gem) alone in patients with resected pancreatic cancer (PC): Updated 5-year overall survival

The APACT trial evaluated the safety and efficacy of adjuvant nab -P + Gem vs Gem alone in patients with resected PC. Between April 2014 and April 2016, 866 patients were randomized. As previously reported, APACT did not meet the primary endpoint of independently assessed disease-free survival (DFS); however, the prespecified sensitivity analysis for median investigator-assessed DFS was 16.6 months with nab -P + Gem and 13.7 months with Gem (HR, 0.82; 95% CI, 0.694–0.965; nominal P=0.0168). The overall survival (OS; secondary endpoint) at the time of the primary analysis trended in favor of nab -P + Gem: median 40.5 vs 36.2 months (427 events; 68% mature; HR, 0.82; 95% CI, 0.680–0.996; nominal P=0.045). The post hoc updated follow-up survival analysis outcomes were consistent with those observed in the primary analysis of nab -P + Gem vs Gem: median 41.8 vs 37.7 months (511 events; 81% mature; HR, 0.82; 95% CI, 0.687–0.973; nominal P=0.0232). Safety outcomes as previously presented were consistent with those reported in the treated population for the entire trial. Here, we present updated 5-year OS in the intent-to-treat population. Treatment-naive patients with histologically confirmed pancreatic adenocarcinoma, macroscopic complete resection (R0 or R1), Eastern Cooperative Oncology Group performance status 0 or 1, and carbohydrate antigen 19-9 levels < 100 U/mL were eligible. Stratification factors were resection status (R0 vs R1), lymph node status (positive vs negative) and region (North America, Europe, and Australia vs. Asia Pacific). Treatment was initiated ≤12 weeks postsurgery. Patients received nab-P 125 mg/m2 + Gem 1000 mg/m2 or Gem 1000 mg/m2 on days 1, 8, and 15 of six 28-day cycles. The primary endpoint was DFS by independent review. Secondary endpoints were OS and safety. Treatment-naive patients with histologically confirmed pancreatic adenocarcinoma, macroscopic complete resection (R0 or R1), Eastern Cooperative Oncology Group performance status of 0 or 1, and carbohydrate antigen 19-9 levels nab -P 125 mg/m2 + Gem 1000 mg/m2 or Gem 1000 mg/m2 on days 1, 8, and 15 of six 28-day cycles. The primary endpoint was DFS by independent review. Secondary endpoints were OS and safety. As of the data cutoff date (9 April 2021), all patients had been followed up for ≥5 years or discontinued from the study. The median follow-up time for OS was 63.2 months. In the intent-to-treat population, 268 and 287 events occurred in the nab -P + Gem and Gem arms, respectively (88% mature). The median OS in the nab -P + Gem arm was 41.8 months compared with 37.7 months in the Gem arm (HR, 0.80; 95% CI, 0.678–0.947; nominal P=0.0091). Five-year OS rates were 38% with nab -P + Gem and 31% with Gem. Patterns of OS in the prespecified subgroups were generally consistent with observations from the intent-to-treat population: R0 (HR, 0.85; 95% CI, 0.698–1.034); R1 (HR, 0.73; 95% CI, 0.534–1.003); LN+ (HR, 0.77; 95% CI, 0.636–0.922); LN− (HR, 0.97; 95% CI, 0.667–1.415). The 5-year OS outcomes in the APACT trial were consistent with those observed in both the primary analysis and the prior post hoc updated analysis for nab -P + Gem vs Gem alone. Although APACT did not meet its primary endpoint of independently assessed DFS in the primary analysis, these OS data suggest improved outcomes with nab -P + Gem.

Update analysis of NEJ009: Gefitinib alone (G) versus gefitinib plus chemotherapy (GCP) for non-small cell lung cancer with mutated EGFR.

9081 Background: NEJ009 study is the first randomized phase III trial that compared gefitinib plus chemotherapy with gefitinib in patients with untreated NSCLC harboring EGFR mutations. We report an updated OS and long-term tolerability analysis, including subgroup analyses focusing on a type of EGFR mutation and metastatic sites. Methods: Patients were randomly assigned to gefitinib (gefitinib 250 mg PO, QD) and GCP regimen (gefitinib 250 mg PO, QD combined with carboplatin AUC 5 and pemetrexed 500 mg/m2 in a 3-week cycle for up to six cycles, followed by concurrent gefitinib and pemetrexed maintenance). This study tested multiple primary endpoints, PFS, PFS2, and OS, which were analyzed using a preplanned hierarchical sequential testing method. Results: Three hundred forty-five patients were randomly assigned (gefitinib, n = 172; GCP, n =170). At latest data cut-off (May 22, 2020), although there was no significant difference in OS between the groups (HR, 0.82; 95% CI, 0.64 to 1.06; P=0.13), GCP still demonstrated significantly better PFS and PFS2 compared to G. The updated median PFS, PFS2, and OS was 11.2 months, 18.0 months, and 38.5 months in the gefitinib group and 20.9 months, 20.9 months, and 49.0 months in the GCP group, respectively. No severe adverse events occurred in the period since the first report. Conclusions: This updated analysis confirmed that the GCP regimen achieved significantly better PFS and PFS2 with an acceptable safety profile compared with gefitinib alone. The efficacy outcome of GCP is more favorable than gefitinib monotherapy as first-line treatment of NSCLC with EGFR mutation. Clinical trial information: UMIN000006340. Clinical trial information: UMIN000006340. [Table: see text]

Five-year overall survival (OS) in COLUMBUS: A randomized phase 3 trial of encorafenib plus binimetinib versus vemurafenib or encorafenib in patients (pts) with BRAF V600-mutant melanoma.

9507 Background: Combined BRAF/MEK inhibitor therapy has demonstrated benefits on progression-free survival (PFS) and OS and is standard of care for the treatment of advanced BRAF V600-mutant melanoma. Here we report a 5-year update from the COLUMBUS trial. Methods: In Part 1 of COLUMBUS, 577 pts with advanced/metastatic BRAF V600-mutant melanoma, untreated or progressed after first-line immunotherapy, were randomized 1:1:1 to encorafenib 450 mg QD + binimetinib 45 mg BID (COMBO450), encorafenib 300 mg QD (ENCO300), or vemurafenib 960 mg BID (VEM). An updated analysis including PFS, OS, objective response rate (ORR; by blinded independent central review), and safety was conducted after minimum follow-up of 65.2 months (mo). Data are as is; study is ongoing. Results: At data cut-off (Sep 15, 2020), there were 131 (68%), 117 (60%), and 145 (76%) deaths in the COMBO450, ENCO300, and VEM treatment arms, respectively. The median OS (95% CI) and 5-year OS rate (95% CI) with COMBO450 were 33.6 (24.4–39.2) mo and 34.7% (28.0–41.5), respectively (median follow-up: 70.4 mo). The 5-year OS rate (95% CI) in COMBO450 pts who had normal lactate dehydrogenase (LDH) levels at baseline was 45.1% (36.5–53.2). Median OS and 5-year OS rates for ENCO300 and VEM, as well as for pts with normal and high LDH levels and &gt; 3 organs involved at baseline, are shown in the table. For COMBO450, ENCO300, and VEM, the 5-year PFS rate was 22.9%, 19.3%, and 10.2%; ORR (95% CI) was 64.1% (56.8–70.8), 51.5% (44.3–58.8), and 40.8% (33.8–48.2); and the median duration of response (DOR) was 18.6, 15.5, and 12.3 mo, respectively. Safety results were consistent with the known tolerability profile of COMBO450. Additional efficacy and updated safety analyses will be presented. Following study drug discontinuation, the most common subsequent treatment in all arms was checkpoint inhibitors. Conclusions: Updated OS and DOR results with COMBO450 demonstrate continued long-term benefits in pts with BRAF V600-mutant melanoma. Clinical trial information: NCT01909453. [Table: see text]