Ongoing phase 1b/2 trials of mosunetuzumab investigating novel treatment regimens for patients with b-cell non-hodgkin lymphoma (nhl)

Background: There is an unmet need for more effective and less toxic treatments for patients (pts) with B-cell NHL. Mosunetuzumab is a CD20/CD3 bispecific antibody that directs T-cells to engage and eliminate CD20+ B-cells. Interim results from a phase 1/1b study show that mosunetuzumab-monotherapy (M) is clinically active with a manageable safety profile in pts with relapsed/refractory (R/R) NHL (Budde et al. ASH 2018). Here we present 3 ongoing phase 1b/2 studies in NHL with mosunetuzumab (Table), 2 in novel combinations, and 1 as monotherapy consolidation after first-line (1L) immunochemotherapy or initial 1L therapy in elderly/unfit pts. Methods: Two randomised, open-label, multicentre combination studies are being conducted to compare the following regimens across B-cell NHL: mosunetuzumab + cyclophosphamide, doxorubicin, vincristine and prednisone (M-CHOP); mosunetuzumab + cyclophosphamide, doxorubicin, and prednisone (M-CHP) + polatuzumab vedotin (M-CHP-pola); or rituximab-CHP-pola in 1L diffuse large B-cell lymphoma (DLBCL); M-pola compared with M-monotherapy, or immunochemotherapy in R/R NHL. A third study is evaluating M-monotherapy in DLBCL pts, either as consolidation after partial response (PR) to 1L immunochemotherapy or as 1L therapy in pts unfit for full-dose chemotherapy. Safety and efficacy data from these studies will further define the role of mosunetuzumab in the treatment of B-cell NHL. NCT03677141 GO40515 Phase 1b: R/R B-cell NHL Phase 2: 1L DLBCL ECOG PS ≤2 Age ≥18 years M + CHOP M + CHP-pola R + CHP-pola NCT03671018 GO40516 R/R B-cell NHL ECOG PS ≤2 Age ≥18 years M + pola M-monotherapy R + bendamustine-pola [DLBCL/transformed follicular lymphoma] or obinutuzumab + bendamustine followed by obinutuzumab maintenance or R-CHOP/CVP [follicular lymphoma] NCT03677154 GO40554 DLBCL ECOG PS ≤2 Group A: age ≥18 years; best response of PR to 1L immunochemotherapy Group B: age ≥80 or 60–79 years + unfit for full-dose chemotherapy Acknowledgement: These studies are funded by F. Hoffmann-La Roche. Third-party medical writing assistance, under the direction of Lihua Budde, was provided by Louise Profit and Russell Craddock of Gardiner-Caldwell Communications, and was funded by F. Hoffmann-La Roche Ltd. This abstract was previously submitted to ASCO 2019. Keywords: CD20; CD3; non-Hodgkin lymphoma (NHL). Disclosures: Budde, L: Consultant Advisory Role: Gilead, Genentech, AstraZeneca; Research Funding: Mustang Therapeutics, Merck & Co, Amgen; Other Remuneration: Gilead, AstraZeneca (speakers' bureau). Babu, S: Employment Leadership Position: Fort Wayne Medical Oncology & Hematology; Consultant Advisory Role: Bristol-Myers Squibb, Alexion Pharmaceuticals; Stock Ownership: Fort Wayne Medical Oncology & Hematology, Lutheran Hospital; Honoraria: Bristol-Myers Squibb, Alexion Pharmaceuticals, Lilly, Bayer, AstraZeneca; Research Funding: Bristol-Myers Squibb, Novartis, Genentech, Inc./Roche, AstraZeneca/MedImmune, HERON, Janssen Oncology, Amgen, Incyte, TG Therapeutics, Seattle Genetics, AbbVie, Lilly, Alexion Pharmaceuticals, Merck, Novartis; Other Remuneration: Alexion Pharmaceuticals (speakers' bureau); Bristol-Myers Squibb, Alexion Pharmaceuticals, Lilly (travel, accommodation and expenses). Lossos, I: Consultant Advisory Role: Seattle Genetics, Janssen Scientific. Alderuccio, J: Consultant Advisory Role: Agios, Inovio Pharmaceuticals, Puma Biotechnology, Foundation Medicine; Honoraria: Targeted Oncology. Chavez, J: Consultant Advisory Role: Genentech, Inc., Novartis, Kite, Bayer, Karyopharm; Other Remuneration: Genentech, Inc., Kite, AstraZeneca (speakers' bureau). Eradat, H: Consultant Advisory Role: Genentech, Inc., Roche, AbbVie; Honoraria: Genentech, Inc., AbbVie, Pharmacyclics, Takeda; Research Funding: Genentech, Inc., AbbVie, Pharmacyclics, Beigene, Kite, Gilead, Juno, ATARA, Miragen, Verastem; Other Remuneration: Genentech, Inc., AbbVie, Pharmacyclics, Takeda (speakers' bureau). Holmes, H: Consultant Advisory Role: Bayer, Celgene, Gilead, Rigel, Janssen, AstraZeneca; Honoraria: Janssen; Research Funding: Kite, Unum, Celgene, Novartis, Genentech, Inc., Seattle Genetics; Other Remuneration: Kite, Seattle Genetics, Rigel (speakers' bureau). Hamadani, M: Consultant Advisory Role: MedImmune, Cellerant Therapeutics, Janssen Research & Development, Incyte Coporation, Pharmacyclics, ADC Therapeutics, Puma Biotechnology; Honoraria: Celgene; Research Funding: Takeda, Spectrum Pharmaceuticals, Otsuka US, Astellas Pharma, Genzyme; Other Remuneration: Genzyme, Celgene (speakers' bureau). Karur, V: Employment Leadership Position: Baylor Scott and White Hospital. Olszewski, A: Employment Leadership Position: Rhode Island Hospital; Research Funding: Roche/Genentech, Inc., TG Therapeutics, Spectrum Pharmaceuticals. Seymour, E: Honoraria: Karyopharm; Research Funding: Karyopharm, Incyte; Other Remuneration: Karyopharm (travel, accommodation and expenses). Althaus, B: Employment Leadership Position: Genentech, Inc.; Stock Ownership: Roche. Medeiros, B: Employment Leadership Position: Roche/Genentech, Inc.; Stock Ownership: Roche/Genentech, Inc. Li, C: Employment Leadership Position: Genentech, Inc.; Stock Ownership: Roche. Kwan, A: Employment Leadership Position: Genentech, Inc./Roche; Stock Ownership: Genentech, Inc./Roche. Wei, M: Employment Leadership Position: Genentech, Inc.; Stock Ownership: Roche. Yin, S: Employment Leadership Position: Genentech, Inc.; Stock Ownership: Genentech, Inc.; Other Remuneration: Genentech, Inc. (travel, accommodation and expenses). O'Hear, C: Employment Leadership Position: Genentech, Inc.; Stock Ownership: Roche. Munoz, J: Consultant Advisory Role: Pharmacyclics LLC, Bayer, Gilead/Kite Pharma, Pfizer, Janssen, Juno/Celgene, Bristol-Myers Squibb; Other Remuneration: Kite Pharma, Gilead, Bayer, Pharmacyclics/Janssen, AstraZeneca (speakers' bureau).