A Safety, Efficacy and Pharmacokinetic Study of BTCT4465A (Mosunetuzumab) as a Single Agent and Combined With Atezolizumab in Non-Hodgkin's Lymphoma (NHL) and Chronic Lymphocytic Leukemia (CLL)

Summary

This is a Phase 1/2 dose-escalation study of BTCT4465A (Mosunetuzumab) administered as a single agent and in combination with atezolizumab in participants with relapsed or refractory B-cell NHL and CLL. The study will consist of a dose-escalation stage and an expansion stage where participants will be enrolled into indication-specific cohorts.

Timeline

Start

2015-09-15

Primary completion

2024-05-21

Completion

2025-09-01

Outcome

Mixed primary results

paper The observed complete response rate was significantly higher than the historical control complete response rate with copanlisib of 14% (p<0·0001), thereby meeting the primary study endpoint. PMID 35803286 ↗

paper CR rate did not reach statistical significance vs the historical control (P = .36). PMID 37067952 ↗

Publications

• Bartlett NL, Sehn LH, Assouline S, Giri P, Kuruvilla J, Schuster SJ, Yoon SS, Fay K, Hess G, Dreyling M, Gutierrez NC, Cybulski E, Sabalvaro F, Penuel E, Teodoro V, Tracy S, Kuruvilla D, Chen J, Wiebking V, Wei MC, Budde LE. Fixed-Duration Subcutaneous Mosunetuzumab in Relapsed/Refractory Follicular Lymphoma: Pivotal Phase 2 Primary Analysis. Am J Hematol. 2026 May;101(5):986-997. doi: 10.1002/ajh.70225. Epub 2026 Mar 20.
• Lewis KL, Assouline SE, Baker R, Bartlett NL, El-Sharkawi D, Giri P, Ku M, Matasar M, Schuster S, Radford J, Wei MC, Yin S, Kwan A, To I, Raghavan V, Budde LE, Cheah CY. Mosunetuzumab monotherapy is active and tolerable in patients with relapsed/refractory Richter transformation. Blood Adv. 2026 May 12;10(9):3011-3019. doi: 10.1182/bloodadvances.2025017914.
• Danilov AV, Kambhampati Thiruvengadam S, Linton K, Cumings K, Chirikov V, Mutebi A, Bains Chawla S, Chhibber A, Rivas Navarro F, Marques Goncalves F, Wang A, Ding Z, Alshreef A, Favaro E, Hoehn D, Sureda A. Indirect comparison of epcoritamab vs chemoimmunotherapy, mosunetuzumab, or odronextamab in follicular lymphoma. Blood Adv. 2025 Aug 12;9(15):3754-3765. doi: 10.1182/bloodadvances.2024015274.
• Li J, Liao MZ, Wilkins J, Penuel E, Wang B, Vadhavkar S, Peng K, Cao J, Li Z, Zhang Y, Li W, Li D, Zhou M, Wei MC, Kwan A, Zhao R, Li C, Li CC, Turner DC. Ethnic Sensitivity Assessment of Mosunetuzumab Pharmacokinetics and Pharmacodynamics in Chinese Patients With Relapsed or Refractory Follicular Lymphoma. Clin Transl Sci. 2025 May;18(5):e70211. doi: 10.1111/cts.70211.
• Chong EA, Penuel E, Napier EB, Lundberg RK, Budde LE, Shadman M, Matasar MJ, Bartlett NL, Flinn IW, Bosch F, Fay K, Goy A, Kumar A, Nastoupil LJ, Wei MC, Wu M, Yin S, Fraietta JA, Chong ER, Schuster SJ. Impact of prior CAR T-cell therapy on mosunetuzumab efficacy in patients with relapsed or refractory B-cell lymphomas. Blood Adv. 2025 Feb 25;9(4):696-703. doi: 10.1182/bloodadvances.2024013640.
• Sehn LH, Bartlett NL, Matasar MJ, Schuster SJ, Assouline SE, Giri P, Kuruvilla J, Shadman M, Cheah CY, Dietrich S, Fay K, Ku M, Nastoupil LJ, Wei MC, Yin S, To I, Kaufman D, Kwan A, Penuel E, Bolen CR, Budde LE. Long-term 3-year follow-up of mosunetuzumab in relapsed or refractory follicular lymphoma after >/=2 prior therapies. Blood. 2025 Feb 13;145(7):708-719. doi: 10.1182/blood.2024025454.
• Ray MD, Kanters S, Beygi S, Best T, Wulff J, Limbrick-Oldfield E, Patel AR, Oluwole OO. Matching-Adjusted Indirect Comparisons of Axicabtagene Ciloleucel to Mosunetuzumab for the Treatment of Relapsed/Refractory Follicular Lymphoma. Transplant Cell Ther. 2024 Sep;30(9):885.e1-885.e11. doi: 10.1016/j.jtct.2024.06.016. Epub 2024 Jun 19.
• Jemaa S, Ounadjela S, Wang X, El-Galaly TC, Kostakoglu L, Knapp A, Ku G, Musick L, Sahin D, Wei MC, Yin S, Bengtsson T, De Crespigny A, Carano RAD. Automated Lugano Metabolic Response Assessment in 18F-Fluorodeoxyglucose-Avid Non-Hodgkin Lymphoma With Deep Learning on 18F-Fluorodeoxyglucose-Positron Emission Tomography. J Clin Oncol. 2024 Sep 1;42(25):2966-2977. doi: 10.1200/JCO.23.01978. Epub 2024 Jun 6.
• Bender B, Li CC, Marchand M, Turner DC, Li F, Vadhavkar S, Wang B, Deng R, Lu J, Jin J, Li C, Yin S, Wei M, Chanu P. Population pharmacokinetics and CD20 binding dynamics for mosunetuzumab in relapsed/refractory B-cell non-Hodgkin lymphoma. Clin Transl Sci. 2024 Jun;17(6):e13825. doi: 10.1111/cts.13825.
• Budde LE, Assouline S, Sehn LH, Schuster SJ, Yoon SS, Yoon DH, Matasar MJ, Bosch F, Kim WS, Nastoupil LJ, Flinn IW, Shadman M, Diefenbach C, Cheah CY, Ma CY, Huang H, Kwan A, Wei MC, Yin S, Bartlett NL. Durable Responses With Mosunetuzumab in Relapsed/Refractory Indolent and Aggressive B-Cell Non-Hodgkin Lymphomas: Extended Follow-Up of a Phase I/II Study. J Clin Oncol. 2024 Jul 1;42(19):2250-2256. doi: 10.1200/JCO.23.02329. Epub 2024 Mar 28.
• Schuster SJ, Huw LY, Bolen CR, Maximov V, Polson AG, Hatzi K, Lasater EA, Assouline SE, Bartlett NL, Budde LE, Matasar MJ, Koeppen H, Piccione EC, Wilson D, Wei MC, Yin S, Penuel E. Loss of CD20 expression as a mechanism of resistance to mosunetuzumab in relapsed/refractory B-cell lymphomas. Blood. 2024 Feb 29;143(9):822-832. doi: 10.1182/blood.2023022348.
• Bosch F, Kuruvilla J, Vassilakopoulos TP, Maio DD, Wei MC, Zumofen MB, Nastoupil LJ. Indirect Treatment Comparisons of Mosunetuzumab With Third- and Later-Line Treatments for Relapsed/Refractory Follicular Lymphoma. Clin Lymphoma Myeloma Leuk. 2024 Feb;24(2):105-121. doi: 10.1016/j.clml.2023.09.007. Epub 2023 Sep 28.
• Sanchez Alvarez J, Jaber M, Blanchet Zumofen MH. Multiple Real-World Data Sources in a Bayesian Framework to Inform Long-Term Survival Estimates of Mosunetuzumab in Patients with Follicular Lymphoma. Oncol Ther. 2023 Dec;11(4):495-511. doi: 10.1007/s40487-023-00245-4. Epub 2023 Oct 18.
• Bartlett NL, Assouline S, Giri P, Schuster SJ, Cheah CY, Matasar M, Gregory GP, Yoon DH, Shadman M, Fay K, Yoon SS, Panizo C, Flinn I, Johnston A, Bosch F, Sehn LH, Wei MC, Yin S, To I, Li CC, Huang H, Kwan A, Penuel E, Budde LE. Mosunetuzumab monotherapy is active and tolerable in patients with relapsed/refractory diffuse large B-cell lymphoma. Blood Adv. 2023 Sep 12;7(17):4926-4935. doi: 10.1182/bloodadvances.2022009260.
• Budde LE, Sehn LH, Matasar M, Schuster SJ, Assouline S, Giri P, Kuruvilla J, Canales M, Dietrich S, Fay K, Ku M, Nastoupil L, Cheah CY, Wei MC, Yin S, Li CC, Huang H, Kwan A, Penuel E, Bartlett NL. Safety and efficacy of mosunetuzumab, a bispecific antibody, in patients with relapsed or refractory follicular lymphoma: a single-arm, multicentre, phase 2 study. Lancet Oncol. 2022 Aug;23(8):1055-1065. doi: 10.1016/S1470-2045(22)00335-7. Epub 2022 Jul 5.
• Budde LE, Assouline S, Sehn LH, Schuster SJ, Yoon SS, Yoon DH, Matasar MJ, Bosch F, Kim WS, Nastoupil LJ, Flinn IW, Shadman M, Diefenbach C, O'Hear C, Huang H, Kwan A, Li CC, Piccione EC, Wei MC, Yin S, Bartlett NL. Single-Agent Mosunetuzumab Shows Durable Complete Responses in Patients With Relapsed or Refractory B-Cell Lymphomas: Phase I Dose-Escalation Study. J Clin Oncol. 2022 Feb 10;40(5):481-491. doi: 10.1200/JCO.21.00931. Epub 2021 Dec 16.

Drugs

Evaluation	Drug	Modality	Dose	Route
Subject	Atezolizumab	Monoclonal antibody	1200 mg	Intravenous
Subject	Mosunetuzumab	Monoclonal antibody	30 mg	Intravenous
Subject	Mosunetuzumab	Monoclonal antibody	45 mg	Intravenous

Indications