Distant metastasis-free survival results from the randomized, phase 2 mRNA-4157-P201/KEYNOTE-942 trial.

被引：34

作者：

Khattak, Adnan ^{[1
,2
]}

Weber, Jeffrey S. ^{[3
]}

Meniawy, Tarek ^{[4
]}

Taylor, Matthew H. ^{[5
]}

Ansstas, George ^{[6
]}

Kim, Kevin B. ^{[7
]}

McKean, Meredith ^{[8
]}

Long, Georgina V. ^{[9
,10
,11
]}

Sullivan, Ryan J. ^{[12
]}

Faries, Mark B. ^{[13
]}

Tran, Thuy ^{[14
]}

Cowey, Charles Lance ^{[15
]}

Medina, Theresa Michelle ^{[16
]}

Segar, Jennifer Margaret ^{[17
]}

Atkinson, Victoria ^{[18
,19
]}

Gibney, Geoffrey Thomas ^{[20
]}

Luke, Jason J. ^{[21
]}

Buchbinder, Elizabeth Iannotti ^{[22
]}

Meehan, Robert S. ^{[23
]}

Carlino, Matteo S. ^{[24
,25
]}

机构：

[1] One Clin Res, Perth, WA, Australia

[2] Edith Cowan Univ, Perth, WA, Australia

[3] NYU Sch Med, Laura & Isaac Perlmutter Canc Ctr, New York, NY USA

[4] Sir Charles Gairdner Hosp, Nedlands, WA, Australia

[5] Earle A Chiles Res Inst, Portland, OR USA

[6] Washington Univ Oncol, St Louis, MO USA

[7] Calif Pacific Med Ctr, Res Inst, San Francisco, CA USA

[8] Tennessee Oncol, Sarah Cannon Res Inst, Nashville, TN USA

[9] Univ Sydney, Melanoma Inst Australia, Sydney, NSW, Australia

[10] Royal North Shore Hosp, Sydney, NSW, Australia

[11] Mater Hosp, Sydney, NSW, Australia

[12] Massachusetts Gen Hosp, Boston, MA USA

[13] Angeles Clin & Res Inst, Los Angeles, CA USA

[14] Yale New Haven Hosp, New Haven, CT USA

[15] Texas Oncol, Baylor Charles A Sammons Canc Ctr, Dallas, TX USA

[16] Univ Colorado, Aurora, CO USA

[17] Univ Arizona, Canc Ctr, Tucson, AZ USA

[18] Princess Alexandra Hosp, Woolloongabba, Qld, Australia

[19] Univ Queensland, Woolloongabba, Qld, Australia

[20] Georgetown Lombardi Comprehens Canc Ctr, Washington, DC USA

[21] UPMC Hillman Canc Ctr, Pittsburgh, PA USA

[22] Dana Farber Canc Inst, Boston, MA USA

[23] Moderna Therapeut, Cambridge, MA USA

[24] Univ Sydney, Westmead Hosp, Melanoma Inst Australia, Sydney, NSW, Australia

[25] Univ Sydney, Blacktown Hosp, Melanoma Inst Australia, Sydney, Australia

来源：

JOURNAL OF CLINICAL ONCOLOGY | 2023年 / 41卷 / 17_SUPPL期

关键词：

261-566-9263; 613-135-2370-7650-2454-5112; 283-232-2351; 281-270-5041-5043; 298-145-222-184-1022-9124; 281-318-6655; 281-318-9499; 6; 4; 3; 2; 242; 10;

D O I：

10.1200/JCO.2023.41.17_suppl.LBA9503

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Background: mRNA-4157 is a novel mRNA-based personalized cancer vaccine which encodes up to 34 patient-specific tumor neoantigens. The open-label randomized Phase 2 mRNA-4157-P201/Keynote-942 trial met its primary endpoint of recurrence free survival (RFS) in patients with resected high-risk stage IIIB/C/D and IV melanoma. The study has shown a statistically significant and clinically meaningful improvement in RFS in the combination therapy compared to pembrolizumab monotherapy, with a reduction in the risk of recurrence or death by 44% (HR = 0.561; 95% CI: (0.309, 1.017); 1-sided p-value of 0.0266). This report provides the first analysis of the secondary efficacy endpoint of distant metastasis-free survival (DMFS). Methods: mRNA-4157-p201 is an ongoing multicenter, open-label, randomized Phase II trial in patients with completely resected, high-risk Stage IIIB/C/D and IV cutaneous melanoma. Patients were randomized 2:1 (stratified by stage) to receive mRNA-4157 in combination with pembrolizumab or pembrolizumab alone. mRNA-4157 (1mg) was administered intramuscularly every 3 weeks for a total of 9 doses and pembrolizumab (200mg) intravenously was given every 3 weeks for up to 18cycles. The primary endpoint was investigator-assessed RFS, defined as local, locoregional, distant recurrence, or new primary melanoma. The secondary endpoint of DMFS was pre-specified and hierarchically tested following positive RFS. All tests were performed at 1-sided alpha = 0.99. Results: 157 patients were randomized to the combination of mRNA-4157 with pembrolizumab (n = 107) or pembrolizumab monotherapy (n = 50). The primary analysis for the primary endpoint occurred after all patients completed a minimum of 12 months on study and 44 RFS events were observed. At a median follow-up of 23 (combination) and 24 (pembrolizumab) months in the primary analysis, RFS events were reported in 22.4% (24/107) of patients in the combination arm and in 40% (20/50) of patients in the monotherapy arm. The 18-month RFS rates (95% CI) were 78.6% (69.0%, 85.6%) vs 62.2% (46.9%,74.3%) in the combination and monotherapy arms respectively. There was also a statistically and clinically significant improvement in DMFS for the combination versus pembrolizumab monotherapy (HR = 0.347; 95% CI: (0.145, 0.828); 1-sided p-value 0.0063). Distant recurrence or death was reported in 8.4% (9/107) and 24% (12/50) of patients, with 18-month DMFS rates (95% CI) were 91.8% (84.2%, 95.8%) vs 76.8% (61.0%, 86.8%) in the combination and monotherapy arm, respectively. Conclusions: mRNA-4157 in combination with pembrolizumab as adjuvant therapy for resected high-risk melanoma significantly prolonged DMFS compared to pembrolizumab. These results provide further evidence that a personalized neoantigen approach is potentially beneficial for cancer patients. A phase 3 randomized study will be initiated in patients with melanoma. Clinical trial information: NCT03897881.

引用

页码：LBA9503 / LBA9503

页数：1