- [Resource Hub](/) - [Publication](/?resource-type=publication#library) - Copanlisib in combination with nivolumab for microsatellite stable colorectal cancer: a phase 1/2 trial # Copanlisib in combination with nivolumab for microsatellite stable colorectal cancer: a phase 1/2 trial Christenson ES, Wala JA, Parkinson R, Collins NB, Jakubowski C, Lin JR, et al. Nature Communications . 2026;17:7114. DOI [10.1038/s41467-026-72985-6](https://doi.org/10.1038/s41467-026-72985-6). How to cite ### AMA Christenson ES, Wala JA, Parkinson R, Collins NB, Jakubowski C, Lin JR, et al. Copanlisib in combination with nivolumab for microsatellite stable colorectal cancer: a phase 1/2 trial. Nat Commun . 2026;17:7114. doi:10.1038/s41467-026-72985-6 ### APA Christenson, E. S., Wala, J. A., Parkinson, R., Collins, N. B., Jakubowski, C., Lin, J.-R., et al. (2026). Copanlisib in combination with nivolumab for microsatellite stable colorectal cancer: a phase 1/2 trial. Nature Communications , 17, 7114. https://doi.org/10.1038/s41467-026-72985-6 ### BibTeX @article{christenson2026copanlisib, title = {Copanlisib in combination with nivolumab for microsatellite stable colorectal cancer: a phase 1/2 trial}, author = {Christenson, E. S. and Wala, J. A. and Parkinson, R. and Collins, N. B. and Jakubowski, C. and Lin, J.-R. and others}, journal = {Nature Communications}, volume = {17}, pages = {7114}, year = {2026}, doi = {10.1038/s41467-026-72985-6} } In a phase 1/2 trial, the pan-PI3K inhibitor copanlisib was paired with the PD-1 inhibitor nivolumab in 39 heavily pretreated patients with metastatic microsatellite stable colorectal cancer — a setting that accounts for roughly 95% of metastatic disease and has historically not responded to single-agent checkpoint blockade. A molecularly defined subgroup achieved remarkable, durable clinical benefit: every partial response occurred in tumors carrying PI3K-pathway alterations, with progression-free survival spanning 24.2 to more than 33.7 months. What set those responders apart was the question the study set out to answer — and answering it meant reading complex immune architecture from small metastatic core biopsies without exhausting the finite tissue a trial depends on. Investigators profiled 38 pre- and on-treatment core biopsies from 20 patients with RareCyte Orion 18-plex multiplex immunofluorescence, reading the tumor immune microenvironment at subcellular resolution from a single 5 μm tissue section. Responders began treatment with more cytotoxic T cells already inside the tumor — a difference Orion could measure directly in scarce biopsy material — and the same imaging traced how those immune cells changed on treatment, and why recruitment into the tumor was not, on its own, enough. [Read publication at Nature Communications](https://doi.org/10.1038/s41467-026-72985-6) ## Key findings - On baseline biopsies, Orion resolved an immune signature that set responders apart. Across the 18 pre-treatment biopsies that met quality control, clinical responders carried significantly higher intratumoral CD3+CD8+ T-cell density and an elevated CD8+/FOXP3+ Treg ratio; and while PIK3CA-mutant tumors were broadly enriched for CD163+ macrophages, patients with a higher ratio of macrophage-to-tumor PD-L1 expression were significantly more likely to achieve a partial response. - Paired biopsies showed treatment pulled T cells into the tumor, yet the tumor’s own signaling blunted the benefit. Intratumoral CD3+CD8+ T-cell infiltration rose in 100% of evaluable paired biopsies — 8 of 8 patients at 6 weeks (Cycle 2 Day 15) — corroborating within tissue the systemic expansion of activated CD8+ T cells that 34-plex mass cytometry (CyTOF) had registered in the blood. But Orion’s spatial view showed recruitment alone was not enough: localized, tumor-intrinsic ERK/MAPK signaling continued to drive resistance. - Orion’s single-section read matched an orthogonal cyclic method on scarce biopsy tissue. Its quantitative T-cell infiltration measurements — from single-pass, 18-plex imaging of one 5 μm FFPE section at subcellular resolution — reached high analytical concordance when cross-validated against serial-section t-CyCIF on a RareCyte CyteFinder platform, so a single imaging round conserved finite core-biopsy material without giving up agreement. ## Orion in the methods “Orion multiplex immunofluorescence (IF) imaging uses specialized fluorophores with narrow excitation and emission spectra to provide for 18-plex IF in a single imaging run. We employed Orion multiplex IF to provide a basic characterization of the immune microenvironment of the full set of available specimens using a previously standardized antibody panel (Supplementary Table 1) and which have been previously validated. Unstained 5 µm thick FFPE slides were deparaffinized and stained with a fluorophore-conjugated IF antibodies. Stained slides were then imaged with our Orion instrument (RareCyte). Raw microscopy images were then stitched together with MCMICRO software.” — Christenson et al., Nature Communications (2026), Methods, “Orion multiplex immunofluorescence” [Back to all resources](/#library) ## Related resources [Article](https://www.selectscience.net/article/advanced-spatial-biology-sheds-new-light-on-therapeutic-research) Orion SelectScience ### Advanced spatial biology sheds new light on therapeutic research [Read Article](https://www.selectscience.net/article/advanced-spatial-biology-sheds-new-light-on-therapeutic-research) [Article](https://www.selectscience.net/editorial-articles/bringing-spatial-biology-to-the-clinic-a-new-lens-on-cancer-biology/?&artID=58147) Orion SelectScience ### Bringing spatial biology to the clinic: “A new lens on cancer biology” [Read Article](https://www.selectscience.net/editorial-articles/bringing-spatial-biology-to-the-clinic-a-new-lens-on-cancer-biology/?&artID=58147) [Article](https://www.selectscience.net/article/how-to-unlock-the-complexity-of-tumor-microenvironments) Orion SelectScience ### How to unlock the complexity of tumor microenvironments [Read Article](https://www.selectscience.net/article/how-to-unlock-the-complexity-of-tumor-microenvironments) [Brochure](https://go.pardot.com/l/455452/2020-07-15/8p7453/455452/1606951069teslfZQe/BR21_101_Orion_Brochure_201202.pdf) Orion ### Orion Spatial Proteomics Platform [View Brochure](https://go.pardot.com/l/455452/2020-07-15/8p7453/455452/1606951069teslfZQe/BR21_101_Orion_Brochure_201202.pdf) [Spec Sheet](https://pardot.rarecyte.com/l/455452/2026-02-24/965v3w/455452/1771949067AeuR6syb/Orion_HT_spec_sheet.pdf) Orion ### Orion HT [View Spec Sheet](https://pardot.rarecyte.com/l/455452/2026-02-24/965v3w/455452/1771949067AeuR6syb/Orion_HT_spec_sheet.pdf) [Spec Sheet](https://pardot.rarecyte.com/l/455452/2025-10-31/961nyb/455452/1761933957WEJWJyeN/2025.07.14___SS___Orion__LE_.pdf) Orion ### Orion LE [View Spec Sheet](https://pardot.rarecyte.com/l/455452/2025-10-31/961nyb/455452/1761933957WEJWJyeN/2025.07.14___SS___Orion__LE_.pdf) [Spec Sheet](https://go.pardot.com/l/455452/2020-07-15/8p742r/455452/1607104572nfrlJouR/DF_24_101_201203_Orion_Datafile.pdf) Orion ### Orion [View Spec Sheet](https://go.pardot.com/l/455452/2020-07-15/8p742r/455452/1607104572nfrlJouR/DF_24_101_201203_Orion_Datafile.pdf) [Research Spotlight](/resources/spatial-profiling-immune-correlates-mss-crc/) Orion 2026 ### Spatial Profiling Uncovers Immune Correlates of Durable Response in Phase 1/2 MSS Colorectal Cancer Trial [Read Spotlight](/resources/spatial-profiling-immune-correlates-mss-crc/) [Publication](https://doi.org/10.1158/2159-8290.CD-26-0171) Orion Cancer Discovery 2026 ### Spatial Integration of Protein and Chromosomal States Reveals Early Copy-Number Changes and Genotype-Associated Immune Neighborhoods in Serous Ovarian Cancer Evolution [View Publication](https://doi.org/10.1158/2159-8290.CD-26-0171) [Publication](https://www.nature.com/articles/s41467-026-74933-w) Orion Nature Communications 2026 ### Multiple human transgenes prolong survival of triple-carbohydrate knockout porcine kidney xenografts in nonhuman primates [View Publication](https://www.nature.com/articles/s41467-026-74933-w) [Video](https://www.youtube.com/watch?v=KOiToZIGN0g) Orion 2026 ### Dr. Tanjina Kader on mapping spatial proteomics and chromosomal changes on the same tissue section [Watch Video](https://www.youtube.com/watch?v=KOiToZIGN0g) [Blog](/resources/multiplex-if-choosing-right-technology/) Orion 2026 ### Understanding Multiplex Immunofluorescence: Choosing the Right Technology for Discovery, Biomarker Development, and Clinical Research [Read Blog](/resources/multiplex-if-choosing-right-technology/)