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-- 5F9 Well-Tolerated in Combination with Rituximab --
-- Durable Responses Observed in DLBCL and Indolent Lymphoma; Median Duration of Response Not Yet Reached --
-- Overall Response Rate (ORR) of 36% Observed in DLBCL and ORR of 61% Observed in Indolent Lymphoma --
-- FDA Feedback Suggests Single-Arm Pivotal Trial May Support Registration of 5F9 in Combination with Rituximab in Heavily Pre-Treated DLBCL Patients, Including Those Ineligible for CAR-T Therapy --
-- Forty Seven to Host Conference Call and Webcast at 8:00 am ET on Monday, June 17, 2019 --
MENLO PARK, Calif., June 15, 2019 (GLOBE NEWSWIRE) -- Forty Seven, Inc., a clinical-stage, immuno-oncology company focused on developing therapies to activate macrophages in the fight against cancer, today announced updated data from its ongoing Phase 1b/2 clinical trial evaluating 5F9 in combination with rituximab for the treatment of relapsed/refractory non-Hodgkin’s lymphoma (r/r NHL), including diffuse large B-cell lymphoma (DLBCL) and indolent lymphoma. The data will be presented in an oral session at the 24th Congress of the European Hematology Association (EHA) in Amsterdam, Netherlands. Also at EHA, Forty Seven will present data from its ongoing Phase 1b clinical trial evaluating 5F9 as a monotherapy and in combination with azacitidine for the treatment of myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML), which were previously presented at the 2019 American Society for Clinical Oncology (ASCO) Annual Meeting.
“Despite advancements in the treatment of newly-diagnosed NHL, there are very limited options for patients with advanced forms of the disease, who have failed multiple lines of treatment or are ineligible for existing therapies due to advanced age, numerous co-morbidities, and/or the diagnosis of aggressive, proliferating disease,” said Justin Kline, M.D., University of Chicago, Department of Medicine, an investigator for the clinical trial. “In treating these patients, our goal is to achieve durable responses and stave off the rapid disease progression that can limit overall survival to a matter of months. As such, I am encouraged by the updated data for 5F9 in combination with rituximab, which showed consistent clinical benefit across a range of patient populations -- including patients who are heavily pre-treated, ineligible for CAR-T therapy or suffering from primary refractory disease -- as well as durable responses in both DLBCL and FL. I am eager to continue evaluating this combination as a well-tolerated, chemotherapy-free regimen, with the potential to induce long-term remissions even in the sickest patients.”
“Today’s announcement marks a significant milestone in our development of 5F9 for the treatment of r/r NHL,” said Chris Takimoto, M.D., Ph.D., F.A.C.P., Chief Medical Officer of Forty Seven, Inc. “The design of our Phase 1b/2 clinical trial allowed us to continue to explore the clinical benefit of 5F9 in combination with rituximab in patients with DLBCL and indolent lymphoma, while also expanding into a subset of older, sicker DLBCL patients who have been deemed ineligible for CAR-T therapy. We are particularly gratified to see meaningful activity in this newly-defined population, which has never before been evaluated in clinical trials, and for whom there are few, if any, effective treatment options available. Importantly, following recent interactions with the U.S. Food and Drug Administration (FDA), we believe we may be able to pursue approval in a heavily pre-treated population, including DLBCL patients who have failed at least two prior lines of therapy or who are ineligible for CAR-T therapy, with a single-arm pivotal study serving as the basis for our BLA filing. These developments bring us closer to achieving our vision of establishing 5F9 as a cornerstone immunotherapy for the treatment of a broad range of cancers.”
Data from the Ongoing Phase 1b/2 Clinical Trial in r/r NHL
Forty Seven’s Phase 1b/2 trial, which is being funded in part by the Leukemia and Lymphoma Society (LLS) through the Therapy Acceleration Program® (TAP), is designed to evaluate 5F9 in combination with rituximab in patients with r/r B-cell NHL, who have failed standard-of-care therapies. All patients received a 1 mg/kg priming dose of 5F9 to mitigate on-target anemia. Patients in the Phase 1b portion of the trial were treated with 5F9 maintenance doses of 10 to 45 mg/kg, and patients in the Phase 2 portion of the trial were treated with 5F9 doses of either 30 or 45 mg/kg. All patients were also administered full doses of rituximab.
As of the data cutoff of May 2019, 115 patients had been treated in the Phase 1b/2 trial, including 70 patients with DLBCL, 41 patients with follicular lymphoma (FL) and four patients with marginal zone lymphoma (MZL). The median number of prior therapies across all patients was three (range one to 10), and 85% of all patients were refractory to a prior rituximab-containing regimen, with 59% of DLBCL patients having primary refractory disease. Additionally, 42 of the 47 DLBCL patients enrolled in the Phase 2 portion of the trial were ineligible for CAR-T therapy (89%).
As of the data cutoff, 5F9 was well-tolerated in combination with rituximab. Adverse events (AEs) were consistent with prior clinical experience. Most AEs were Grade 1 or Grade 2, and the most commonly-reported AEs were expected CD47-mechanism-based effects on red blood cells, which led to a temporary and reversible anemia, and infusion-site reactions. No autoimmune-related AEs were observed, nor were any significant late safety signals observed in patients treated with 5F9 for up to 24 months. No maximum tolerated dose was reached with up to 45 mg/kg of 5F9 dosing. Eight out of 115 patients discontinued treatment due to an AE (7%).
Clinical Activity Data
As of the data cutoff, 97 patients were evaluable for response assessment, including 21 relapsed/refractory DLBCL patients who were treated in the Phase 1b portion of the study, 38 DLBCL patients who were treated in the Phase 2 portion of the study and 38 indolent lymphoma patients (35 patients with FL and three patients with MZL).
|Best Overall Response||
N = 21 (%)
N = 38 (%)
3 Prior Lines of Therapy
N = 39 (%)
|Primary refractory disease or
relapsed/refractory to ≥ 2 prior
lines of therapy
relapsed/refractory to ≥ 2
prior lines of therapy and
ineligible for CAR-T
|Subgroup analysis of
combined Phase 1b and
Phase 2 Data
|ORR||10 (48)||11 (29)||15 (38)|
|CR||7 (33)||2 (5)||7 (18)|
|PR||3 (14)||9 (24)||8 (20)|
|SD||4 (19)||3 (8)||4 (10)|
Among patients treated in the Phase 1b portion of the trial, the median duration of response has not been reached, with a median follow-up of over 13.8 months. This includes one patient who has remained in a durable complete response (CR) for more than 24 months.
Phase 1b + 2
FL N = 35; MZL N = 3 (%)
|Relapsed/refractory to ≥ 2 prior lines of therapy|
Among patients treated in the Phase 1b portion of the trial, the median duration of response has not been reached with a median follow-up of over 21 months. This includes the patient who has remained in a durable CR for more than 28 months.
Additionally, 5F9 tumor penetrance was evaluated at 30 and 45 mg/kg as a key pharmacodynamic endpoint. Data show that the 30 mg/kg maintenance dose of 5F9 saturated the tumor microenvironment similarly to 45 mg/kg, with similar efficacy. As a result, a 30 mg/kg maintenance dose of 5F9 was selected as the recommended dose for use in future clinical studies.
Clinical Development Plans for 5F9 in r/r NHL
Based on feedback from a Type C meeting with the FDA in May 2019, Forty Seven believes that data from a single arm pivotal study evaluating ORR and durability may be sufficient to support the registration of 5F9 in combination with rituximab in patients with r/r DLBCL who have failed at least two prior lines of therapy, including those who have been deemed CAR-T ineligible. The Company is currently finalizing the operational components of the proposed registrational study, including details on trial design and chemistry, manufacturing and controls (CMC), and will provide a detailed update in the second half of 2019.
In parallel, the Company will continue ongoing efforts to evaluate 5F9 as part of additional combination regimens for patients with DLBCL, including in patients in earlier lines of treatment. This includes the planned triplet regimen of 5F9, rituximab and atezolizumab, which Forty Seven is evaluating in collaboration with Genentech, and the planned triplet regimen of 5F9, rituximab and acalabrutinib, which Forty Seven is evaluating in collaboration with Acerta Pharma, in addition to potential studies of 5F9 in combination with other targeted antibodies.
Forty Seven will also evaluate opportunities to advance 5F9 in combination with rituximab for patients with indolent lymphoma.
Data from the Ongoing Phase 1b Clinical Trial in MDS and AML
As Forty Seven previously presented at the 2019 ASCO Annual Meeting in June 2019, data from the ongoing Phase 1b clinical trial of 5F9 in MDS and AML showed an ORR of 100% and a CR rate of 55% in higher-risk MDS patients treated with 5F9 in combination with azacitidine and an ORR of 64% and a CR/complete response with incomplete blood count recovery (CRi) rate of 50% in untreated AML patients treated with 5F9 in combination with azacitidine. In addition, the combination was well-tolerated, with no evidence of increased toxicities compared to azacitidine alone.
Based on the favorable safety profile and encouraging clinical activity observed in this Phase 1b clinical trial, expansion cohorts have been initiated in patients with both higher-risk MDS and untreated AML with 5F9 in combination with azacitidine. In addition, based on feedback from a Type B meeting with the FDA in May 2019, Forty Seven believes that data from a single pivotal study may be sufficient to support the registration of 5F9 in combination with azacitidine in patients with untreated, higher-risk MDS. The Company is finalizing the details of the proposed registrational study, and will provide a detailed update in the second half of 2019.
Investor Conference Call and Webcast Information
Forty Seven will host a live conference call and webcast on Monday, June 17, 2019 at 8:00 a.m. ET to review the clinical data presented at EHA. The conference call may be accessed by (866) 953-0780 (domestic) or (630) 652-5854 (international), and by referring to conference ID 3236239. A webcast of the conference call will also be in the Investors section of the Forty Seven website at www.fortyseveninc.com. The archived webcast will be available approximately two hours after the conference call and will be available for 30 days following the call.
5F9 is a monoclonal antibody against CD47 that is designed to interfere with recognition of CD47 by the SIRPα receptor on macrophages, thus blocking the "don't eat me" signal used by cancer cells to avoid being ingested by macrophages. Forty Seven, Inc. is initially developing 5F9, an investigational medicine, for the treatment of patients with solid tumors, acute myeloid leukemia, non-Hodgkin's lymphoma and colorectal cancer. 5F9 has been granted Fast Track designation by the U.S. Food and Drug Administration for the treatment of relapsed or refractory diffuse large B-cell lymphoma and follicular lymphoma, two forms of B-cell non-Hodgkin's lymphoma, and Orphan Drug designation by the U.S. Food and Drug Administration and European Medicines Agency for the treatment of acute myeloid leukemia.
About Forty Seven Inc.
Forty Seven, Inc. is a clinical-stage immuno-oncology company that is developing therapies targeting cancer immune evasion pathways based on technology licensed from Stanford University. Forty Seven’s lead program, 5F9, is a monoclonal antibody against the CD47 receptor, a “don’t eat me” signal that cancer cells commandeer to avoid being ingested by macrophages. This antibody is currently being evaluated in multiple clinical studies in patients with solid tumors, myelodysplastic syndrome, acute myeloid leukemia, non-Hodgkin’s lymphoma, ovarian cancer and colorectal carcinoma.
Forward Looking Statements
Statements contained in this press release regarding matters that are not historical facts are "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995. Words such as "may," "will," "expect," "anticipate," "estimate," "intend," “potential,” “believe” and similar expressions (as well as other words or expressions referencing future events, conditions, or circumstances) are intended to identify forward-looking statements. These statements include those related to the overall advancement of 5F9 in clinical trials; the potential of 5F9 as a monotherapy and in combination with azacitidine for the treatment of MDS and AML; the potential of 5F9 as a tolerable treatment option for patients with MDS and AML as a monotherapy and in combination; the sufficiency of the Company’s single arm pivotal trial design and results from such trial for FDA registration of 5F9 in combination with azacitidine for the treatment of patients with untreated higher-risk MDS; Forty Seven’s plans to continue development of 5F9 as a monotherapy and in combination with azacitidine; the potential of 5F9 in combination with rituximab for the treatment of r/r NHL, including DLBCL, and indolent lymphoma; the sufficiency of the Company’s single arm pivotal trial design evaluating ORR and durability and results from such trial for FDA registration of 5F9 in combination with rituximab in patients with r/r DLBCL; and Forty Seven’s plans to continue development of 5F9 in triplet combination with rituximab and atezolizumab and acalabrutinib, as well as in combination with other targeted antibodies.
Because such statements are subject to risks and uncertainties, actual results may differ materially from those expressed or implied by such forward-looking statements. The product candidates that Forty Seven develops may not progress through clinical development or receive required regulatory approvals within expected timelines or at all. In addition, clinical trials may not confirm any safety, potency or other product characteristics described or assumed in this press release. Such product candidates may not be beneficial to patients or successfully commercialized. The failure to meet expectations with respect to any of the foregoing matters may have a negative effect on Forty Seven's stock price. Additional information concerning these and other risk factors affecting Forty Seven's business can be found in Forty Seven's periodic filings with the Securities and Exchange Commission at www.sec.gov. These forward-looking statements are not guarantees of future performance and speak only as of the date hereof, and, except as required by law, Forty Seven disclaims any obligation to update these forward-looking statements to reflect future events or circumstances.
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