Phase 1b/2, open-label, multicenter, dose escalation and expansion trial of intratumoral SD 101 in combination with pembrolizumab in patients with metastatic melanoma

Date

09 Oct 2016

Session

Poster display

Presenters

Antoni Ribas

Citation

Annals of Oncology (2016) 27 (6): 359-378. 10.1093/annonc/mdw378

Authors

A. Ribas1, R. Gonzalez2, J. Drabick3, S. Kummar4, S. Agarwala5, J. Nemunaitis6, R. Coffman7, C.J. Berman8, E. Schmidt9, E. Chartash10, C. Guiducci7, A. Candia11, R. Janssen12

Author affiliations

  • 1 Department Of Medicine, David Geffen School of Medicine at UCLA, 90095 - Los Angeles, CA/US
  • 2 Medicine/ Medical Oncology, University of Colorado Cancer Center Anschutz Cancer Pavilion, 80045 - Aurora/US
  • 3 Medical Oncology, Penn State Hershey Medical Center, Hershey/US
  • 4 Phase I Clinical Research, Division Of Oncology, Stanford University, Palo Alto/US
  • 5 Medical Oncology, St Lukes, Easton/US
  • 6 Oncology, Mary Crowley Cancer Research Center, Dallas/US
  • 7 Discovery, Dynavax Technologies, Berkeley/US
  • 8 Clinical Research, Dynavax Technologies, 94710 - Berkeley/US
  • 9 Clinical, Merck Co, Kenilworth/US
  • 10 Clinical Development, Merck, Kenilworth/US
  • 11 Preclinical Development, Dynavax Technologies, Berkeley/US
  • 12 Clinical Research, Dynavax, 94710 - Berkeley/US
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Background

SD-101 is a synthetic Class C CpG-ODN that stimulates plasmacytoid dendritic cells to release interferon-alpha and mature into efficient antigen presenting cells. SD-101 in combination with low dose radiation has demonstrated abscopal activity in indolent B-cell lymphoma (Levy et al AACR 2016). Pre-clinically, in a CT26 mouse model, SD-101 in combination with an anti-PD-1 induced T cell infiltration and durable complete responses in all treated animals (Campos et al, AACR 2016). Pembrolizumab is a PD-1 inhibitor that has been approved for the treatment of metastatic melanoma.

Methods

The MEL-01 trial (NCT02521870) is assessing the safety and preliminary efficacy of SD-101 + pembrolizumab in unresectable stage IIIC-IV melanoma. Phase 1b is a modified 3 + 3 design of 3 dose levels of SD-101 (2, 4, and 8 mg) followed by a phase 2 dose expansion (n = 85). SD-101 is injected into a tumor lesion weekly X 4 followed by q 3 weekly X 3. Pembrolizumab dose is 200 mg IV q 3 weeks. Biopsies of the injected tumor are taken pretreatment and on treatment. Tumor responses are assessed using RECIST v1.1.

Results

In the phase 1b study, 5 patients were enrolled in the 2 mg group and 5 in the 4 mg group. Treatment was well tolerated; there were no DLTs. Adverse events associated with SD-101 were flu-like symptoms the evening following an injection that were treated with over-the-counter medications. No increased toxicity of the combination of drugs has been observed. At 12 weeks, in the 2 mg group, there were 2 PRs, 1 SD, 1 PD (at day 22) and 1 not yet available. One of the patients with a PR had a tumor biopsy that was negative for melanoma. Five patients were enrolled in late April 2016 in the 4 mg cohort; response data will be available by October. Additionally, mechanistic insight into therapeutic activity obtained through examination of tumor biopsies by IHC, PD-L1 expression, and NanoString RNA expression profiling will be presented.

Conclusions

Preliminary results suggest that the combination of SD-101 + pembrolizumab shows activity in metastatic melanoma.

Clinical trial identification

Clinical trials.gov NCT02521870; Date of initial posting: 30 July 2015

Legal entity responsible for the study

Dynavax Technologies, Berkeley, California

Funding

Dynavax Technologies, Berkeley, California and Merck and Company, Inc, Kenilworth, New Jersey

Disclosure

A. Ribas: Consultant to Merck with honoraria paid to UCLA. R. Gonzalez: Receiving grants and consulting for MERCK, BMS, Novartis, Amgen, Roche/Genentech. J. Drabick: Consultant at Merck and Novartis. J. Nemunaitis: Founder of two companies, Gradalis and Strike which are not related to this research R. Coffman: Full time employee of Dynavax. C.J. Berman: Paid consultant for Dynavax Technologies. E. Schmidt: Full time employee of Merck. E. Chartash: Employee of Merck. C. Guiducci, A. Candia, R. Janssen: Employee of Dynavax. All other authors have declared no conflicts of interest.

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