Updates in lung cancer - nsclc 2024 pptx

Lung cancer updates 2025

1. ESMO Updates : Lung Cancer (NSCLC)

2. CheckMate 77T: Phase III Trial of Neoadjuvant Nivolumab + Chemotherapy vs Placebo + Chemotherapy With Adjuvant Nivolumab or Placebo in Stage II-IIIB NSCLC Supported by educational grants from AstraZeneca; Bristol Myers Squibb; Daiichi Sankyo, Inc.; Exelixis, Inc.; Gilead Sciences, Inc.; Lilly; and Regeneron Pharmaceuticals, Inc. CCO Independent Conference Highlights* of the European Society for Medical Oncology 2023 Congress October 20-24, 2023 *CCO is an independent medical education company that provides state-of-the-art medical information to healthcare professionals through conference coverage and other educational programs. Provided by Clinical Care Options, LLC

3. CheckMate 77T: Background Neoadjuvant nivolumab + chemotherapy is the standard of care for eligible patients with resectable NSCLC 1 A perioperative approach of administering nivolumab with neoadjuvant chemotherapy and as postsurgical adjuvant therapy improved pCR and survival in patients with resectable stage IIIA-B NSCLC in an open-label phase II trial 2 Randomized, double-blind phase III CheckMate 77T study was undertaken to compare neoadjuvant nivolumab + chemotherapy followed by adjuvant nivolumab against neoadjuvant chemotherapy + placebo followed by adjuvant placebo in patients with resectable stage II-IIIB NSCLC 3 1. NCCN. Clinical practice guidelines in oncology: non-small cell lung cancer. v4.2023. 2. Provencio. NEJM. 2023;389:504-513. 3. Cascone. ESMO 2023. Abstr LBA1.

4. CheckMate 77T: Study Design Global randomized, double-blind phase III trial Primary endpoint: EFS by BICR Secondary endpoints: pCR by BIPR, MPR by BIPR, OS, safety Exploratory analyses: EFS by pCR/MPR, EFS by adjuvant treatment Cascone. ESMO 2023. Abstr LBA1. R esectable, previously untreated stage IIA (>4 cm)-IIIB (N2) NSCLC; ECOG PS 0/1; no EGFR mutations or ALK alterations (N = 461) Nivolumab 360 mg Q3W + Chemotherapy* Q3W x 4 cycles (n = 229) Stratified by histology (nonsquamous vs squamous), stage (II vs III), PD-L1 status (≥1% vs <1% vs NE/indeterminate) Placebo Q3W + Chemotherapy* Q3W x 4 cycles (n = 232) R adiologic restaging and surgery (≤ 6 wk post neoadjuvant treatment) Nivolumab 480 mg Q4W for 1 yr Placebo Q4W for 1 yr *Cisplatin or carboplatin + pemetrexed or paclitaxel or docetaxel.

5. CheckMate 77T: Baseline Characteristics Cascone. ESMO 2023. Abstr LBA1. Characteristic Nivo + CT/Nivo (n = 229) CT + Pbo/Pbo (n = 232) Median age, yr (range) 66 (37-83) 66 (35-86) Male, n (%) 167 (73) 160 (69) Geographic region, n (%) Europe Asia North America Rest of world 123 (54) 65 (28) 23 (10) 18 (8) 127 (55) 50 (22) 21 (9) 34 (15) ECOG PS, n (%) 1 147 (64) 82 (36) 141 (61) 91 (39) Disease stage, n (%) IIA-B IIIA-B 81 (35) 146 (64) 81 (35) 149 (64) Histology, n (%) Squamous Nonsquamous 116 (51) 113 (49) 118 (51) 114 (49) Characteristic, n (%) Nivo + CT/Nivo (n = 229) CT + Pbo/Pbo (n = 232) Current/former smoker 212 (93) 205 (88) Tumor PD-1 expression Not evaluable < 1% ≥1% 1-49% ≥50% 8 (4) 93 (41) 128 (56) 83 (36) 45 (20) 11 (5) 93 (40) 128 (55) 76 (33) 52 (22) Platinum therapy type Cisplatin Carboplatin 55 (24) 167 (73) 42 (18) 180 (78)

6. CheckMate 77T: Treatment and Surgical Outcomes Cascone. ESMO 2023. Abstr LBA1. Outcome Nivo + CT/Nivo (n = 229) CT + Pbo/Pbo (n = 232) Completed neoadjuvant treatment, n (%) 194 (85) 205 (89) Received definitive surgery, n (%) 178 (78) 178 (77) Received adjuvant treatment, n (%) 142 (62) 152 (66) Adjuvant treatment doses, median (range) 13 (1-13) 13 (1-13) Adjuvant treatment completed, n (%) 85 (60) 92 (60) Extent of resection,* n/N (%) Lobectomy Pneumonectomy 142/178 (80) 16/178 (9) 128/178 (72) 24/178 (14) Completeness of resection, n/N (%) R0 R1/R2 159/178 (89) 19/178 (11) 161/178 (90) 17/178 (10) *Patients may have had ≥1 type of surgery.

7. CheckMate 77T: EFS Overall and by Stage Cascone. ESMO 2023. Abstr LBA1. All Patients Nivo + CT/Nivo (n = 229) CT + Pbo/Pbo (n = 232) HR (97.36% CI) P Value Median EFS (BICR), mo (95% CI) NR (28.9-NR) 18.4 (13.6-28.1) 0.58 (0.42-0.81)* .00025 12-mo EFS, % 18-mo EFS, % 73 70 59 50 Stage II Nivo + CT/Nivo (n = 81) CT + Pbo/Pbo (n = 81) HR (95% CI) Median EFS (BICR), mo (95% CI) NR (22.6-NR) NR (24.2-NR) 0.81 (0.46-1.43) 12-mo EFS, % 78 73 Stage III Nivo + CT/Nivo (n = 148) CT + Pbo/Pbo (n = 149) HR (95% CI) Median EFS (BICR), mo (95% CI) 30.2 (26.9-NR) 13.4 (9.8-17.7) 0.51 (0.36-0.72) 12-mo EFS, % 71 52 *EFS per investigator assessment: HR: 0.56 (95% CI: 0.41-0.76).

8. CheckMate 77T: EFS by PD-L1 Expression Benefit of Nivo + CT/Nivo vs CT + Pbo/Pbo was seen in subgroups including </≥ 65 yr, ECOG PS 0/1, N0/N1, N2 single-station/multistation, squamous/nonsquamous, and cisplatin/carboplatin Cascone. ESMO 2023. Abstr LBA1. PD-L1 <1% PD-L1 ≥1% Nivo + CT/Nivo (n = 93) CT + Pbo/Pbo (n = 93) Nivo + CT/Nivo (n = 128) CT + Pbo/Pbo (n = 128) Median EFS, mo (95% CI) 29.0 (21.4-NR) 19.8 (13.9-NR) NR (28.9-NR) 15.8 (9.3-35.1) HR (95% CI) 0.73 (0.47-1.15) 0.52 (0.35-0.78) 12-mo EFS, % 69 67 76 54 PD-L1 1%-49% (n = 159) PD-L1 ≥50% (n = 97) Nivo + CT/Nivo CT + Pbo/Pbo Nivo + CT/Nivo CT + Pbo/Pbo Median EFS, mo 30.2 28.1 NR 8.0 HR (95% CI) 0.76 (0.46-1.25) 0.26 (0.12-0.55)

9. CheckMate 77T: Pathologic Responses and EFS Analyses Cascone. ESMO 2023. Abstr LBA1. Pathologic Response Nivo + CT/Nivo, n (%) (n = 229) CT + Pbo/Pbo, n (%) (n = 232) Difference Between Arms, % OR (95% CI) pCR 58 (25.3) 11 (4.7) 20.5 6.64 (3.40-12.97) MPR 81 (35.4) 28 (12.1) 23.2 4.01 (2.48-6.49)

10. CheckMate 77T: Safety Any grade surgery-related AEs: 73 (41%) for Nivo + CT/Nivo vs 69 (39%) for CT + Pbo/Pbo Grade 3/4 surgery-related AEs: 21 (12%) in each arm Cascone. ESMO 2023. Abstr LBA1. AE Outcome Nivo + CT/Nivo (n = 229) CT + Pbo/Pbo (n = 232) Overall Neoadjuvant Adjuvant Overall Neoadjuvant Adjuvant Any G3/4 Any G3/4 Any G3/4 Any G3/4 Any G3/4 Any G3/4 All AEs, % 97 47 95 34 87 20 98 43 96 27 80 15 TRAEs, % 89 32 86 27 50 8 87 25 85 23 30 3 AEs leading to discontinuation, % 25 14 13 9 14 5 11 6 7 4 5 1 TRAEs leading to discontinuation, % 19 11 11 8 10 4 7 5 5 4 3 All SAEs, % 42 28 21 14 22 13 31 20 15 8 15 9 Treatment-related SAEs, % 19 14 14 10 7 4 10 6 8 5 1 1 Treatment-related deaths: 2 during neoadjuvant period in Nivo + CT/Nivo arm (grade 5 pneumonitis and grade 4 pneumonitis)

11. CheckMate 77T: Immune-Mediated AEs Cascone. ESMO 2023. Abstr LBA1. Immune-Mediated AE, % Nivo + CT/Nivo (n = 229) CT + Pbo/Pbo (n = 232) Grade 1/2 Grade 3/4 Grade 1/2 Grade 3/4 Hypothyroidism/thyroiditis 11 2 Pneumonitis 3 2 < 1 1 Rash 4 1 1 Hyperthyroidism 4 < 1 2 Nephritis/renal dysfunction 2 1 Diarrhea/colitis 1 1 1 Adrenal insufficiency 2 Diabetes mellitus 1 Hypophysitis 1 < 1 Hypersensitivity <1 Hepatitis < 1

12. CheckMate 77T: Investigators’ Conclusions Neoadjuvant nivolumab + chemotherapy followed by surgery and adjuvant nivolumab was associated with a significant, clinically meaningful improvement in EFS vs neoadjuvant chemotherapy + placebo in patients with resectable NSCLC (HR: 0.58; P = .00025) 12 month EFS 73% vs 59% pCR : 25.3% vs 4.7%; MPR: 35.4% vs 12.1% EFS benefit with perioperative nivolumab was observed In patients with pCR after neoadjuvant therapy In patients eligible for adjuvant therapy, regardless of pCR status In patients unable to receive adjuvant therapy No new safety findings and similar rates of completed surgeries between arms Outcomes support perioperative nivolumab as a potential new treatment option for patients with resectable NSCLC Cascone. ESMO 2023. Abstr LBA1.

13. Lung cancer – staging TNM 8 th edition

14. Principles of surgical resection : Sublobar resection - Segmentectomy and wedge resection should be strongly considered for peripheral T1ab, N0 tumors. Sublobar resection should achieve parenchymal resection margins ≥2 cm or ≥ the size of the nodule. Sublobar resection should also sample appropriate N1 and N2 lymph node stations unless not technically feasible without substantially increasing the surgical risk. T3 (invasion) and T4 local extension tumors require en -bloc resection of the involved structure with negative margins.

15. Complete resection requires free resection margins, systematic node dissection or sampling, and the highest mediastinal node negative for tumor. The Role of Surgery in Patients with N2 NSCLC: The role of surgery in patients with pathologically documented N2 disease remains controversial. Neoadjuvant chemoradiotherapy is used in one-third of the NCCN Member Institutions, while neoadjuvant chemotherapy is used in the other two-thirds.

16. All patients should be evaluated for preoperative therapy, with strong consideration for nivolumab or pembrolizumab + chemotherapy for those patients with tumors ≥4 cm(T2b) or node positive and no contraindications to immune checkpoint inhibitors. After surgical evaluation, patients likely to receive adjuvant chemotherapy may be treated with induction systemic therapy as an alternative.

17. Adjuvant chemotherapy in resected NSCLC stage 2-3 : Cisplatin based doublet - LACE meta analysis. Adjuvant immunotherapy in resected NSCLC stage 2-3 post adjuvant chemotherapy : Atezolizumab – Impower010 Permbrolizumab – PEARLS/KEYNOTE 091

18. Neo-adjuvant immuno-chemotherapy : Nivolumab - CheckMate 816 Perioperative chemo-immunotherapy : Permbrolizumab – Keynote 671

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20. ESMO Updates : Lung Cancer (NSCLC)

21. Volume 35, Issue 1 p77-90 January 2024

22. Background: Amivantamab plus carboplatin - pemetrexed (chemotherapy) with and without lazertinib demonstrated antitumor activity in patients with refractory epidermal growth factor receptor (EGFR)-mutated advanced non-small cell lung cancer (NSCLC) in phase I studies. These combinations were evaluated in a global phase III trial.

23. Patients and methods: A total of 657 patients with EGFR-mutated (exon 19 deletions or L858R) locally advanced or metastatic NSCLC, after disease progression on Osimertinib, were randomized 2 : 2 : 1 to receive amivantamab – Lazertinib - chemotherapy, chemotherapy, or amivantamab - chemotherapy.

24. Patients with brain metastases were eligible provided intracranial disease was clinically stable, asymptomatic, and on stable doses of steroids; prior definitive treatment with radiation or surgery was not required. The dual primary endpoints were progression-free survival (PFS) of amivantamab - chemotherapy and amivantamab – Lazertinib - chemotherapy versus chemotherapy. Secondary endpoints included objective response rate, duration of response, overall survival, PFS after first subsequent therapy, symptomatic PFS, intracranial PFS, and safety.

25. Amivantamab was administered intravenously at 1400 mg (1750 mg for body weight >80 kg) weekly for the first 4 weeks, and then 1750 mg (2100 mg for body weight >80 kg) every 3 weeks starting at cycle 3 (week 7). The first amivantamab infusion was split over 2 days, with 350 mg on cycle 1, day 1 and the remainder on cycle 1, day 2. Lazertinib was administered orally at 240 mg daily.

26. Chemotherapy was administered intravenously at the beginning of every cycle, with pemetrexed at 500 mg/m2 administered every cycle and carboplatin at area under the curve 5 for the first four cycles. Amivantamab , lazertinib , and pemetrexed treatments were to be continued until disease progression or lack of clinical benefit as deemed by the investigator.

27. Assessment : Disease assessments occurred at baseline, at 6 weeks after randomization, then every 6 (+/-1) weeks for the first 12 months, and then every 12 (+/-1) weeks thereafter until disease progression was confirmed by blinded independent central review.

28. Demographic details :

29. Results : PFS ( BICR)

30. Figure 1. Shown are Kaplan-Meier estimates of progression-free survival assessed by blinded independent central review (A) and investigator assessment (B). The efficacy analysis set included all randomized patients. Tick marks indicate censoring of data. CI, confidence interval. PFS (investigator assessed)

31. Amivantamab - chemotherapy and amivantamab - lazertinib -chemotherapy significantly improved PFS versus chemotherapy, with a 52% and 56% lower risk of disease progression or death, respectively. It is notable that amivantamab - chemotherapy demonstrated similar intracranial PFS advantages over chemotherapy as amivantamab – Lazertinib - chemotherapy.

32. NCCN Guidelines :

33. Resistance to Osimertinib : Acquired resistance mechanisms to EGFR-TKIs can be broadly grouped into EGFR-dependent or EGFR-independent mechanisms. 

34. Amivantamab - Amivantamab is a bispecific antibody that can bind to immune cell receptors. - Post-transcriptional modifications affect its binding to FcγRs. - The asparagine residue in position 297 is linked to a core structure that can be modified with fucose, galactose, or sialic acid. - Amivantamab is produced in a mammalian cell line using recombinant DNA technology with low levels of fucose. - The level of fucosylation affects the binding to FcγRIIIa on natural killer cells and macrophages.

35. ASC4FIRST: Phase III Trial of Asciminib vs Investigator-Selected TKIs in Newly Diagnosed CML Supported by educational grants from GSK, Lilly, Novartis Pharmaceuticals Corporation, and Sanofi. CCO Independent Conference Coverage* of the 2024 American Society of Clinical Oncology Annual Meeting, May 31 - June 4, 2024 *CCO is an independent medical education company that provides state-of-the-art medical information to healthcare professionals through conference coverage and other educational programs. Provided by Clinical Care Options, LLC Slide credit: clinicaloptions.com

36. ASC4FIRST: Background Patients with newly diagnosed CML need long-term treatment options that optimize efficacy, safety, and tolerability 1,2 Standard TKIs often do not yield optimal responses Prolonged use of second-generation TKIs is associated with toxicities that negatively affect patient adherence Asciminib is first-in-class BCR::ABL1 allosteric inhibitor that specifically targets ABL myristoyl pocket 3 Received FDA accelerated approval for patients with Ph+ CML-CP previously treated with ≥2 TKIs, and Ph+ CML-CP with T315I mutation 4 Current analysis of phase III ASC4FIRST study reports primary efficacy and safety of asciminib vs investigator-selected TKIs in newly diagnosed CML-CP 5,6 1. Jabbour. Expert Rev Anticancer Ther. 2013;13:1433. 2. Chow. Leuk Lymphoma. 2021;62:1203. 3. Yeung. Blood. 2022;139:3474. 4. Asciminib PI. 5. Hughes. ASCO 2024. Abstr LBA6500. 6. Hochhaus. NEJM . 2024;[Epub].

37. Site of action of Asciminib

38. Multicenter, open-label, randomized phase III trial (data cutoff: Nov 28, 2023) Primary endpoints: MMR at Wk 48, MMR at Wk 48 in imatinib stratum Key secondary endpoints: MMR at Wk 96, safety, CHR, CCyR, PFS, OS, EFS, PK ASC4FIRST: Study Design Patients aged ≥18 yr with ND Ph+ CML in chronic phase; no prior therapy, including TKIs*; ECOG PS 0-1 (N = 405) 5 yr after last patient receives first dose or until PD, discontinuation, or unacceptable toxicity Oral Asciminib 80 mg QD (n = 201) Investigator-Selected TKI † (n = 204) Hochhaus. NEJM. 2024;[Epub]. Hughes. ASCO 2024. Abstr LBA6500. NCT04971226. Stratified by EUTOS long-term survival score (low vs intermediate vs high), prerandomization investigator-selected TKI for comparator arm (imatinib vs 2G TKI) *Hydroxyurea and/or anagrelide allowed; ≤2 wk of imatinib, nilotinib, dasatinib, or bosutinib allowed. † Includes 400 mg imatinib QD with food, nilotinib 300 mg BID during fasting conditions, bosutinib 400 mg QD with food, or dasatinib 100 mg QD ± food . 1:1

39. ASC4FIRST: Baseline Characteristics Hochhaus. NEJM. 2024;[Epub]. Hughes. ASCO 2024. Abstr LBA6500. Characteristic Asciminib IS-TKI Characteristic All Patients (n = 201) Imatinib Stratum (n = 101) 2G TKI Stratum (n = 100) All Patients (n = 204) Imatinib Stratum (n = 102) 2G TKI Stratum (n = 102) Median age, yr (range) 52 (18-79) 56 (21-79) 43 (18-76) 50.5 (19-86) 54.5 (20-86) 43 (19-83) Age group, % 18 to <65 yr 65 to <75 yr ≥75 yr 77.1 17.9 5.0 68.3 23.8 7.9 86.0 12.0 2.0 76.0 16.7 7.4 68.6 21.6 9.8 83.3 11.8 4.9 Male, % 65.2 61.4 69.0 61.3 63.7 58.8 Framingham CV risk score, % Low (<10%) Intermediate (10%-20%) High (≥20%) 54.2 15.9 29.9 40.6 20.8 38.6 68.0 11.0 21.0 54.9 21.6 23.5 39.2 28.4 32.4 70.6 14.7 14.7 EUTOS long-term survival score, % Low Intermediate High 60.7 27.9 11.4 61.4 29.7 8.9 60.0 26.0 14.0 61.3 27.9 10.8 62.7 29.4 7.8 59.8 26.5 13.7

40. ASC4FIRST: Molecular Responses With Asciminib vs IS-TKIs Patients, % All Patients Imatinib Stratum 2G TKI Stratum Characteristic Asciminib (n = 201) IS-TKI (n = 204) Asciminib (n = 101) IS-TKI (n = 102) Asciminib (n = 100) IS-TKI (n = 102) MMR at Wk 48 67.7* 49.0* 69.3 † 40.2 † 66.0 ‡ 57.8 ‡ EMR at Wk 12 89.6 70.1 88.1 59.8 91.0 80.4 MR 4 at Wk 48 38.8 20.6 42.6 14.7 35.0 26.5 MR 4.5 at Wk 48 16.9 8.8 17.8 4.9 16.0 12.7 Null hypothesis rejected if adjusted P ≤.025. *Common treatment difference: 18.9% (95% CI: 9.6%-28.2%; P < .001). † Common treatment difference: 29.6% (95% CI: 16.9%-42.2%; P <.001). ‡ Common treatment difference: 8.2% (95% CI: 5.1%-21.5%). Hochhaus. NEJM. 2024;[Epub]. Hughes. ASCO 2024. Abstr LBA6500.

41. ASC4FIRST: MMR at Wk 48 by Subgroup — Asciminib vs IS-TKI (Full Set Analysis) Median follow-up: Asciminib: 16.3 mo IS-TKI: 15.7 mo For all subgroups, MMR at Wk 48 favored asciminib in imatinib and 2G TKI full set analyses Hochhaus. NEJM. 2024;[Epub]. Hughes. ASCO 2024. Abstr LBA6500. Subgroup IS-TKI Asciminib Treatment Difference (95% Cl) IS-TKI Better Asciminib Better no. of patients/total no. (%) All patients ELTS based on randomization data Low Intermediate High Sex Female Male Race Asian White Other Age category 18 to <65 yr 65 to <75 yr ≥75 yr 100/204 (49) 72/125 (58) 21/57 (37) 7/22 (32) 43/79 (54) 57/125 (46) 41/90 (46) 56/110 (51) 3/4 (75) 75/155 (48) 19/34 (56) 6/15 (40) 136/201 (68) 88/122 (72) 36/56 (64) 12/23 (52) 45/70 (64) 91/131 (69) 58/90 (64) 75/108 (69) 3/3 (100) 100/155 (65) 27/36 (75) 9/10 (90) 18.6 (9.2 to 28.1) 14.5 (2.8 to 26.3 27.4 (9.7 to 45.2) 20.4 (-7.9 to 48.6) 9.9 (-5.8 to 25.6) 23.9 (12.1 to 35.6) 18.9 (4.6 to 33.2) 18.5 (5.8 to 31.3) 25.0 (-17.4 to 67.4) 16.1 (5.2 to 27.0) 19.1 (-2.8 to 41.0) 50.0 (19.0 to 81.0) -40 -20 20 40 60 80 100

42. ASC4FIRST: Grade ≥3 Toxicity, Treatment Modification, and Hematologic Adverse Events Asciminib IS-TKI AE, % All Patients (n = 200) Imatinib Stratum (n = 99) 2G TKI Stratum (n = 102) Grade ≥3 38.0 44.4 54.9 Led to discontinuation 4.5 11.1 9.8 Led to dose adjustment or interruption Increased lipase Diarrhea Lymphopenia Pleural effusion 30.0 1.5 -- -- -- 39.4 -- 2.0 2.0 -- 52.9 -- -- -- 2.0 Median dose intensity: Asciminib 80.0 mg/day Imatinib 400.0 mg/day Nilotinib 595.1 mg/day Dasatinib 98.9 mg/day Bosutinib 341.8 mg/day Hematologic AE, % Asciminib (n = 200) Imatinib Stratum (n = 99) 2G TKI Stratum (n = 102) Any Gr Gr ≥3 Any Gr Gr ≥3 Any Gr Gr ≥3 Thrombocytopenia 28.0 13.0 28.3 6.1 34.3 13.7 Neutropenia 25.0 10.0 31.1 17.2 34.3 17.6 Anemia 11.5 1.5 26.3 5.1 22.5 5.9 Lymphopenia 6.0 2.5 16.2 5.1 6.9 1.0 Hochhaus. NEJM. 2024;[Epub]. Hughes. ASCO 2024. Abstr LBA6500.

43. ASC4FIRST: Nonhematologic Adverse Events AE, % Asciminib (n = 200) Imatinib Stratum (n = 99) 2G TKI Stratum (n = 102) Any Gr Gr ≥3 Any Gr Gr ≥3 Any Gr Gr ≥3 Diarrhea 15.5 26.3 25.5 1.0 Constipation 9.5 4.0 12.7 1.0 Nausea 9.0 21.2 17.6 Vomiting 5.5 12.1 5.9 Fatigue 14.0 0.5 14.1 1.0 17.6 Headache 13.5 0.5 8.1 21.6 Myalgia 13.0 0.5 17.2 14.7 Rash 13.0 10.1 2.0 21.6 1.0 Muscle spasms 2.0 19.2 4.9 Periorbital/ face edema 1.0 20.2 1.0 1.0 AE, % Asciminib (n = 200) Imatinib Stratum (n = 99) 2G TKI Stratum (n = 102) Any Gr Gr ≥3 Any Gr Gr ≥3 Any Gr Gr ≥3 Increased lipase 11.5 3.0 14.1 1.0 10.8 3.9 Increased ALT 7.0 2.0 6.1 2.0 18.6 7.8 Increased AST 2.0 0.5 6.1 1.0 14.7 2.9 Increased ALP 5.5 13.1 5.9 Increased blood bilirubin 2.5 2.0 1.0 10.8 Arterial occlusive events were infrequent Asciminib: 2 (1%) any grade 1 grade ≥3: cerebrovascular accident No events reported in imatinib stratum 2G TKI: 2 (2%) any grade 1 grade ≥3: myocardial infarction Hochhaus. NEJM. 2024;[Epub]. Hughes. ASCO 2024. Abstr LBA6500.

44. ASC4FIRST: Investigators’ Conclusions First-line asciminib showed superior efficacy vs all SoC TKIs, including imatinib and 2G TKIs, in patients with newly diagnosed CML in chronic phase Significantly higher MMR at Wk 48 with asciminib vs IS-TKI Significantly higher MMR at Wk 48 with asciminib vs preselected imatinib stratum Favorable safety and tolerability profile with asciminib, suggesting better benefit-to-risk ratio vs SoC TKIs Grade ≥3 AEs: 38% (asciminib) vs 44.4% (imatinib) vs 54.9% (2G TKIs); 49.8% in all comparators Investigators concluded that asciminib could potentially become treatment of choice for newly diagnosed patients with CML in chronic phase Hochhaus. NEJM. 2024;[Epub]. Hughes. ASCO 2024. Abstr LBA6500.

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