Citations 2
Phase 1b/2 study of BMS-813160, a CCR2/5 dual antagonist, in combination with chemotherapy or nivolumab in patients with advanced pancreatic or colorectal cancer
Folprecht, G., Varghese, Anna M. , Gutiérrez, Martín , Noel, Marcus Smith , Chen, Eric, Dayyani, Farshid, Davis, S Lindsey, BasuMallick, Atrayee, Garrido-Laguna, Ignacio, Osawa, Mayu, O’Brien, Shaun, Novosiadly, Ruslan D., Xu, Ke, Greenawalt, Danielle , Dutta, Santanu, Victor, Christina Twyman Saint, Lenz, Heinz-Josef, Folprecht, Gunnar , Chen, Eric , Osawa, Mayu , Le, Dung Thi , Trikalinos, Nikolaos A. , Chen, Eric X. , Dayyani, Farshid , Davis, S Lindsey, Wee, Wen , Garrido‐Laguna, Ignacio , O’Brien, Shaun, Dutta, Santanu , Victor, Christina Twyman-Saint , Lenz, Heinz‐Josef
Journal for ImmunoTherapy of Cancer | January 22, 2026 | Volume: 14 | Issue: 1 | Pages: e011284
Background Cysteine–cysteine chemokine receptors 2 (CCR2) and 5 (CCR5) contribute to immune suppression in tumor microenvironments. CCR2 and CCR5 antagonists have demonstrated antitumor activity in pancreatic ductal adenocarcinoma (PDAC) and colorectal cancer (CRC), respectively. This phase 1b/2, open-label study evaluated BMS-813160, a CCR2/5 dual antagonist, in combination with chemotherapy±nivolumab in advanced PDAC or metastatic CRC. Methods Part 1 included patients with metastatic untreated (first-line (1L)) PDAC, 1L CRC, or previously treated (second or third line (2/3L)) microsatellite stable (MSS) CRC. Patients received 2 weeks of BMS-813160 monotherapy (300 mg two times a day, 600 mg once daily, 300 mg once daily, or 150 mg once daily) and then BMS-813160+chemotherapy (gemcitabine+nab-paclitaxel (gem/nabP; 1L PDAC), 5-fluorouracil+leucovorin+irinotecan (FOLFIRI; 1L CRC)), or nivolumab (2/3L MSS CRC). Part 2 included patients with metastatic 1L PDAC or 2L CRC. Patients received BMS-813160 300 mg two times a day+gem/nabP±nivolumab (1L PDAC), BMS-813160 300 mg two times a day or 150 mg once daily+FOLFIRI (2L CRC), or chemotherapy alone. Primary endpoints were safety and pharmacodynamics (Part 1) and efficacy (Part 2). Results In Part 1, 22 of 75 (29%) and 54 of 72 (72%) patients experienced a treatment-related adverse event during monotherapy lead-in and overall, respectively. Two dose-limiting toxicities (rash and pericardial effusion with pericarditis, both grade 3) occurred. In Part 2, patients with 1L PDAC who received BMS-813160 300 mg two times a day+gem/nabP+nivolumab achieved an overall response rate (ORR) of 37% (13/35); the median duration of response (DOR) was 45 weeks (95% CI 26.1 to not evaluable). ORRs with BMS-813160 300 mg two times a day+gem/nabP and gem/nabP alone were 26% (9/35) and 28% (9/32), respectively; median DORs were 121 and 31 weeks, respectively. Progression-free survival rates at 24 weeks were 56% (BMS-813160 300 mg two times a day+gem/nabP+nivolumab), 56% (BMS-813160 300 mg two times a day+gem/nabP), and 50% (gem/nabP). ORRs in 2L CRC were 19% (6/32; BMS-813160 300 mg two times a day+FOLFIRI), 13% (4/32; BMS-813160 150 mg once daily+FOLFIRI), and 27% (7/26; FOLFIRI). Conclusions In 1L PDAC, BMS-813160 300 two times a day+gem/nabP±nivolumab demonstrated durable antitumor response and was well tolerated. BMS-813160 combination regimens were tolerable in other cohorts, but clinical efficacy was not demonstrated. Trial registration number NCT03184870 .
Clinical and Translational Results of a Phase II, Randomized Trial of an Anti–IGF-1R (Cixutumumab) in Women with Breast Cancer That Progressed on Endocrine Therapy
Gradishar, William J. , Sparano, Joseph A. , Chuang, Ellen, Northfelt, Donald W. , Schwartz, Gary N. , Youssoufian, Hagop , Tang, Shande, Novosiadly, Ruslan D., Forest, Amélie, Nguyen, Tuan S., Cosaert, Jan , Grebennik, Dmitri, Haluska, Paul , Yardley, Denise Aysel , Layman, Rachel M. , Sparano, Joseph A
Clinical Cancer Research | August 31, 2015 | Volume: 22 | Issue: 2 | Pages: 301-309
Abstract Purpose: This phase II trial evaluated the efficacy and safety of cixutumumab, a human anti–insulin-like growth factor receptor 1 (IGF-1R) monoclonal IgG1 antibody, and explored potential biomarkers in postmenopausal women with hormone receptor–positive breast cancer. Experimental Design: Patients with hormone receptor–positive breast cancer that progressed on antiestrogen therapy received (2:1 randomization) cixutumumab 10 mg/kg and the same antiestrogen (arm A) or cixutumumab alone (arm B) every 2 weeks (q2w). Primary endpoint was progression-free survival (PFS); secondary endpoints included overall survival (OS) and safety. Correlative analyses of IGF-1R, total insulin receptor (IR), and IR isoforms A (IR-A) and B (IR-B) expression in tumor tissue were explored. Results: Ninety-three patients were randomized (arm A, n = 62; arm B, n = 31). Median PFS was 2.0 and 3.1 months for arm A and arm B, respectively. Secondary efficacy measures were similar between the arms. Overall, cixutumumab was well tolerated. IGF-1R expression was not associated with clinical outcomes. Regardless of the treatment, lower IR-A, IR-B, and total IR mRNA expression in tumor tissue was significantly associated with longer PFS [IR-A: HR, 2.62 (P = 0.0062); IR-B: HR, 2.21 (P = 0.0202); and total IR: HR, 2.18 (P = 0.0230)] and OS [IR-A: HR, 2.94 (P = 0.0156); IR-B: HR, 2.69 (P = 0.0245); and total IR: HR, 2.72 (P = 0.0231)]. Conclusions: Cixutumumab (10 mg/kg) with or without antiestrogen q2w had an acceptable safety profile, but no significant clinical efficacy. Patients with low total IR, IR-A, and IR-B mRNA expression levels had significantly longer PFS and OS, independent of the treatment. The prognostic or predictive value of IR as a biomarker for IGF-1R–targeted therapies requires further validation. Clin Cancer Res; 22(2); 301–9. ©2015 AACR.