Study of Imprime PGG and Pembrolizumab in Advanced Melanoma and Triple Negative Breast Cancer

Summary

Objective: To determine the Overall Response Rate (ORR) to Imprime PGG + pembrolizumab in subjects with advanced melanoma or metastatic TNBC Safety: To characterize the safety of Imprime PGG + pembrolizumab given in combination Hypothesis: Restore (for melanoma) or enhance (for TNBC) sensitivity to checkpoint inhibitors (CPI) by appropriate and effective stimulation of the subject's innate and adaptive immune systems in those subjects who have failed 1st line therapy The study will incorporate Simon's optimal 2-stage design with sample size fixed at 12 subjects each in Stage 1 for advanced melanoma and for Triple Negative Breast Cancer (TNBC) subjects. The safety criterion of ≤ 4 (or ≤ 33%) subjects with Grade 3/4 adverse events in Cycle 1 within either tumor type must be met in order to proceed to Stage 2. The starting dose is 4 mg/kg for Imprime PGG. In the event there are a total of \> 4 (or \> 33%) of subjects with Grade 3/4 adverse events in Cycle 1, the dose of Imprime PGG will be reduced to 2 mg/kg, and Stage 1 will be repeated at a dose of 2 mg/kg with an additional cohort of n=12 subjects. For the dose that meets the safety criterion in Stage 1, at least 1 response in melanoma subjects and 2 responses in TNBC subjects amongst the 12 subjects within each tumor type must be observed in order to proceed to Stage 2. Stage 2 will enroll an additional 17 subjects with melanoma, and 30 subjects with TNBC. For the dose that meets the Stage 1 safety criterion, success will be declared if at least 4 amongst the total of up to 29 subjects with melanoma, and 13 amongst the total of up to 42 subjects with TNBC achieve an objective response.

Timeline

Start

2017-02-22

Primary completion

2020-12-31

Completion

2020-12-31

Publications

• Background Alison Stopeck, Michele Anne Gargano, Nick Niles, Blaine Rathmann, Michael Jon Chisamore, Nandita Bose, and Jose Luis Iglesias. A multicenter, open-label, phase 2 study of odetiglucan (IMPRIME PGG) and pembrolizumab in patients with metastatic breast cancer (mBCA) who have progressed through prior hormonal therapy. Journal of Clinical Oncology. 2022; Volume 40, Number 16_suppl. https://doi.org/10.1200/JCO.2022.40.16_suppl.TPS1115
• Background Chan ASH, Kangas TO, Qiu X, Uhlik MT, Fulton RB, Ottoson NR, Gorden KB, Yokoyama Y, Danielson ME, Jevne TM, Michel KS, Graff JR, Bose N. Imprime PGG Enhances Anti-Tumor Effects of Tumor-Targeting, Anti-Angiogenic, and Immune Checkpoint Inhibitor Antibodies. Front Oncol. 2022 May 26;12:869078. doi: 10.3389/fonc.2022.869078. eCollection 2022.
• Results Steven O'Day, Virginia F. Borges, Bartosz Chmielowski, Ruta D. Rao, Maysa M. Abu-Khalaf, Alison Stopeck, Petros Nikolinakos, Melinda L. Telli, Bin Xie, Montaser F. Shaheen, Paulette Mattson, Michele Anne Gargano, Joanna Cox, Vassiliki Karantza, Michael Jon Chisamore, Bruno Osterwalder, Nandita Bose, Mark T. Uhlik, and Jeremy Graff. An open label, multicenter phase II study combining imprime PGG (PGG) with pembrolizumab (P) in previously treated metastatic triple-negative breast cancer (mTNBC). Journal of Clinical Oncology. 2019; Volume 37, Number 15_suppl. https://doi.org/10.1200/JCO.2019.37.15_suppl.2550
• Results Uhlik M, et al. Response and clinical benefit assessment of the combination of the Dectin-1 agonist Imprime PGG and anti-PD-1 Pembrolizumab in chemotherapy-resistant metastatic triple negative breast cancer. San Antonio Breast Cancer Symposium. 2019. PD-02.
• Results Breast Cancer Plenary Session: O'Day S, et al. A phase 2 trial of pembrolizumab and a novel innate immune activator, Imprime PGG, in metastatic triple negative breast cancer. AACR 2020. (#10531)
• Results Late Breaking Abstract: Chan ASH, et al. Clinical benefit evident with early immunopharmacodynamic responses in prior-checkpoint failed metastatic melanoma patients treated with Imprime PGG and Pembrolizumab. SITC 2019. (#P862)
• Stopeck AT, Abu-Khalaf M, Borges V, Chmielowski B, Rao R, Xie B, Dudek AZ, Mina L, O'Shaughnessy J, Chisamore M, Mattson P, Gargano M, Cox J, Osterwalder B, Drees J, Harrison B, Chan ASH, Qiu X, Ottoson N, Bose N, Uhlik M, Graff J, Iglesias J. Phase 2 trial of imprime and pembrolizumab immunotherapy in metastatic triple negative breast cancer patients who have progressed beyond first line chemotherapy. J Immunol. 2025 Jul 1;214(7):1529-1538. doi: 10.1093/jimmun/vkaf079.

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