2018 ASCO Annual Meeting!
Session: Melanoma/Skin Cancers
Type: Poster Session
Time: Monday June 4, 1:15 PM to 4:45 PM
Location: Hall A
Session: Melanoma/Skin Cancers
Type: Poster Discussion Session
Time: Monday June 4, 4:45 PM to 6:00 PM
A phase 2 study to evaluate the safety and efficacy of Intratumoral (IT) injection of the TLR9 agonist IMO-2125 (IMO) in combination with ipilimumab (ipi) in PD-1 inhibitor refractory melanoma.
2018 ASCO Annual Meeting
Poster Board Number:
Poster Discussion Session (Board #342)
J Clin Oncol 36, 2018 (suppl; abstr 9515)
Author(s): Adi Diab, Shah Rahimian, Cara L. Haymaker, Chantale Bernatchez, Robert Hans Ingemar Andtbacka, Marihella James, Douglas Buckner Johnson, Joseph Markowitz, Ravi Murthy, Igor Puzanov, Montaser F. Shaheen, Suzanne Swann; Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX; Idera Pharmaceuticals, Inc., Exton, PA; The University of Texas MD Anderson Cancer Center, Houston, TX; Huntsman Cancer Institute at the University of Utah, Salt Lake City, UT; Vanderbilt University Medical Center, Nashville, TN; The Ohio State University Wexner Medical Center, Columbus, OH; Department of Interventional Radiology, The University of Texas MD Anderson Cancer Center, Houston, TX; University of New Mexico Comprehensive Cancer Center, Albuquerque, NM; Idera Pharmaceuticals, Inc., Cambridge, MA
Background: PD-1/L1 inhibitors have transformed MM treatment, however many patients (pts) remain refractory. Subsequent treatment options including ipi offer modest benefit (~13% respond) (Long, SMR 2016). IT IMO, a Toll-like receptor 9 agonist, may improve response to ipi by activating innate and adaptive immune responses to overcome immune escape. Tumor biopsies obtained from both injected/local and uninjected/distant lesions during earlier studies show maturation of the mDC1 subset (CD1c+CD303-), upregulation of PD-L1 by tumor cells, and an IFNα response gene signature. On treatment( week 8) biopsies of uninjected/distant tumors show expression of CD56+ and Ki67+ effector CD8+T cells in responding pts, indicative of an abscopal effect. Initial clinical experience with IMO + ipi is promising resulting in the selection of 8mg as the RP2D. Here we report an analysis of the first 15 subjects that received 1+ doses of study drugs. Methods: This is a phase 2 study for adults with unresectable or MM refractory to a PD-1 inhibitor pts are eligible if they have an accessible tumor for IT administration of IMO. 8mg IMO is administered to a single tumor during weeks 1,2,3,5,8, and 11 along with ipi per the product label. The primary endpoint is overall response rate (ORR) using a 2-stage design. Results: A total of 24 pts have been treated with IMO + ipi including pts that received injections to deep visceral lesions and lymph nodes. Grade 3 /4 Immune-related AE were observed in 6 subjects [hypophysitis (N = 2), hepatitis (1), Gastritis (1), Guillain-Barre syndrome (1), Colitis (1), Neutropenia (1)]. These responded well to standard measures. Of 24 pts treated at the RP2D of 8mg, 15 were assessed for response with 47% ORR of and 67% disease control rate (1 Complete Response, 6 Partial Response(3 confirmed), 3 Stable disease). Phase 2 accrual is ongoing. Conclusions: IMO + ipi is a robust strategy to revive the immune response in PD-1/L1resistant tumors and the demonstrated substantial clinical benefit including durable responses in this clinically challenging pt population. This data supports the initiation of a phase 3 study compared to ipi alone. Clinical trial information: NCT02644967