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Poster Discussion session - Melanoma and other skin tumours

3745 - Phase 1b/2, open label, multicenter, study of the combination of SD-101 and pembrolizumab in patients with advanced melanoma who are naïve to anti-PD-1 therapy

Date

20 Oct 2018

Session

Poster Discussion session - Melanoma and other skin tumours

Topics

Clinical Research;  Immunotherapy;  Melanoma

Presenters

Georgina Long

Authors

G.V. Long1, M. Milhem2, A. Amin3, C.J. Hoimes4, T. Medina5, R.M. Conry6, C. Lao7, G. Daniels8, S. Reddy9, I. Mehmi10, R.H.I. Andtbacka11, M. Barve12, M. Shaheen13, T. Tueting14, M. Chisamore15, B. Xing16, A. Candia17, E. Gamelin18, R. Janssen16, A. Ribas19

Author affiliations

  • 1 Medical Oncology, Melanoma Institute Australia, University of Sydney, 2060 - North Sydney/AU
  • 2 Medicine, University of Iowa, 52242 - Iowa City/US
  • 3 Medical Oncology, Levine Cancer Institute, NC 28204 - Charlotte/US
  • 4 Medical Oncology, Case Western Reserve University / University Hospitals, 44106 - Cleveland/US
  • 5 Medicine/medical Oncology, University of Colorado Cancer Center, Aurora/US
  • 6 Hematology And Medical Oncology, UAB School of Medicine, Alabama/US
  • 7 Medicine, University of Michigan Health System, Ann Arbor/US
  • 8 Medicine, University of California, San Diego, San Diego/US
  • 9 Medicine, Stanford University School of Medicine, Stanford/US
  • 10 Mary Babb Randolph Cancer Center, West Virginia University, Morgantown/US
  • 11 Surgical oncology, Huntsman Cancer Institute, 84112 - Salt Lake City/US
  • 12 Oncology, Mary Crowley Cancer Research, 75230 - Dallas/US
  • 13 Medicine, University of Arizona Cancer Center North, Tucson/US
  • 14 Dermatology, University Hospital Madgeburg, Madgeburg/DE
  • 15 Clinical research, Oncology, Merck & Co, Kenilworth/US
  • 16 Clinical Development, Dynavax Technologies Corporation, 94710 - Berkeley/US
  • 17 Discovery, Dynavax Technologies Corporation, 94710 - Berkeley/US
  • 18 Clinical Development, Dynavax Technologies Corporation, 94618 - Berkeley/US
  • 19 Department Of Medicine, Jonsson Comprehensive Cancer Center at UCLA, 90095-1781 - Los Angeles/US
More

Resources

Abstract 3745

Background

SD-101 is a synthetic CpG-ODN agonist of TLR9. Pembrolizumab is a PD-1 inhibitor. SYNERGY-001/KEYNOTE-184 (DV3-MEL-01) assesses the safety and preliminary efficacy of the combination of SD-101 and pembrolizumab in unresectable stage IIIC-IV melanoma.

Methods

SD-101 was evaluated as 2 mg/lesion injected into 1-4 lesions and 1 or 8 mg/lesion injected into 1 lesion as 4 weekly doses followed by 7 doses Q3W. Pembrolizumab was administered as 200 mg IV Q3W. Scans were performed every 9 weeks. Responses were assessed per investigator using RECIST v1.1. Responses and Kaplan-Meier analyses of PFS in the ITT population were compared for patients who received ≤ 2 mg/lesion with 8 mg/lesion.

Results

87 patients (1 mg: n=3; 2 mg: n=44; 8 mg: n=40) have been enrolled with similar baseline characteristics: median age 66 years; male: 68%; stage: IIIC=21%; IVM1a/b=52%; IVM1c=28%; LDH > ULN: 21%; treatment naïve: 71%; PD-L1 negative tumors: 49%. SD-101 safety profile comprises flu-like symptoms. Most frequent grade ≥3 treatment-related AEs were headache (8%), myalgia (7%), malaise (6%), fatigue (6%), chills (6%) and injection-site pain (7%). Immune-related AEs were reported in 17%. One unrelated death occurred in the 8 mg group. The best overall response (ORR) in the ≤ 2 mg group (n=47) was 66% (95% CI: 52, 78) (CR: 11%) and in the 8 mg group (n=40) was 48% (95% CI: 33, 63) (CR: 5%) with responses in both injected and non-injected lesions. ORR in 57 patients with baseline PD-L1 expression data was: PD-L1 positive: ≤ 2 mg=75% (12/16); 8 mg= 62% (8/13); PD-L1 negative: ≤ 2 mg=85% (11/13); 8 mg=33% (5/15); PD-L1 pending: ≤ 2 mg=44% (8/18); 8 mg = 50% (6/12). PFS was higher in the ≤ 2 mg group (median PFS: ≤ 2 mg=not reached [15.2+ months]; 8 mg=10.4 months, p = 0.034; 6 month PFS rate: ≤ 2 mg=86%; 8 mg=62%). Median follow up in this ongoing study is 4.9 months in the ≤ 2 mg group and 7.3 months in the 8 mg group. Tumor biopsies at Day 29 show increases in CD8+, cytotoxic T cells, and NK cells over baseline.

Conclusions

The TLR9 innate immune stimulant, SD-101, in combination with pembrolizumab is showing promising high response rates and prolonged PFS especially in patients who receive lower dose SD-101. The combination has been well tolerated.

Clinical trial identification

NCT02521870

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