1187P - A Phase 1/2 trial of intratumoral (i.t.) IMO-2125 (IMO) in combination with checkpoint inhibitors (CPI) in PD-(L)1-refractory melanoma

Date 10 September 2017
Event ESMO 2017 Congress
Session Poster display session
Topics Cancer in Adolescents
Cancer Immunology and Immunotherapy
Melanoma and other Skin Tumours
Presenter Adi Diab
Citation Annals of Oncology (2017) 28 (suppl_5): v403-v427. 10.1093/annonc/mdx376
Authors A. Diab1, C. Haymaker2, M. Uemura2, R. Murthy3, M. James4, J. Geib5, M. Cornfeld5, S. Swann5, C. Yee4, J. Wargo4, R. Amaria4, S. Patel4, H. Tawbi4, I. Glitza4, S. Woodman4, W. Hwu4, M.A. Davies4, W. Overwijk4, C. Bernatchez2, P. Hwu6
  • 1Medical Oncology, MD Anderson Cancer Center, 77030-4095 - Houston/US
  • 2Melanoma Medical Oncology - Research, MD Anderson Cancer Center, 77030-4095 - Houston/US
  • 3Interventional Radiology Department, The University of Texas MD Anderson Cancer Center, 77030 - Houston/US
  • 4Department Of Melanoma Medical Oncology, MD Anderson Cancer Center, 77030-4095 - Houston/US
  • 5Clinical Science, Idera Pharmaceuticals, 19341 - Exton/US
  • 6Medical Oncology, MD Anderson Cancer Center, 77030 - Houston/US

Abstract

Background

CPI have transformed melanoma treatment, however many patients remain refractory and subsequent treatment options are limited. IMO, a Toll-like receptor 9 agonist, may improve response to CPI by activating innate and adaptive immune responses to overcome immune escape. Initial clinical experience with IMO + ipi is promising (Uemera, ASCO-SITC 2017). Dose-finding is now complete and is the basis for this updated report.

Methods

Adults with unresectable or metastatic melanoma refractory to a PD-(L)1 inhibitor are eligible if they have tumor accessible to biopsy. IMO is administered i.t. to a single tumor at escalating doses during weeks 1,2,3,5,8, and 11 along with ipi or pem per the product label. The primary endpoint of Phase 1 is safety and for Phase 2 is overall response rate using a 2-stage design. Serial biopsies are obtained from both the injected and a non-injected lesion for immune analysis.

Results

A total of 22 subjects have been treated with either IMO-ipi (N = 18) or IMO-pem (N = 4) and dose-escalation is now complete for the IMO-ipi arm. Dose-limiting toxicities have not been reported. Immune-related AE were observed in 4 IMO-ipi subjects [hypophysitis (N = 2), hepatitis (1), colitis (1)]. These responded well to standard measures. Of 9 patients treated at the RP2D of 8mg, 6 have experienced clinical benefit (1CR, 1PR, 1uPR, 3 SD). Biopsies show maturation of the mDC1 subset (CD1c+CD303-), upregulation of PD-L1 by malignant cells, and an IFNα response gene signature. Biopsies of uninjected tumors show expression of CD56+ and Ki67+ effector CD8+T cells in responding patients, indicative of an abscopal effect. Phase 2 accrual using the 8 mg IMO dose is ongoing.

Conclusions

IMO + ipi is a viable strategy to revive the immune response in CPI-resistant tumors and shows preliminary clinical activity worthy of further development.

Clinical trial identification

NCT02644967

Legal entity responsible for the study

Idera Pharmaceuticals

Funding

Idera Pharmaceuticals

Disclosure

J. Geib, S. Swann: Employment by Idera Pharmaceuticals. M. Cornfeld: Employment at Idera Pharmaceuticals. All other authors have declared no conflicts of interest.