Completed dose-escalation shows combination
of AFM13 and pembrolizumab is well-tolerated; 3-month ORR compares
favorably to historical ORR of pembrolizumab alone
Additional preclinical data presented on
BCMA-targeting NK cell engager AFM26
Heidelberg, Germany, December 11, 2017 - Affimed
N.V. (Nasdaq: AFMD), a clinical stage biopharmaceutical company
focused on discovering and developing highly targeted cancer
immunotherapies, today announced the presentation of clinical and
preclinical data on its tetravalent, bispecific natural killer (NK)
cell engagers at the 59th American Society of Hematology
(ASH) Annual Meeting and Exposition 2017 in Atlanta, GA.
Phase 1b study of AFM13 in combination
with pembrolizumab (NCT02665650)A poster presentation
featured data from the completed dose-escalation part of Affimed's
ongoing Phase 1b study to evaluate the safety and tolerability of
the combination of the Company's lead product candidate AFM13 with
pembrolizumab (Keytruda®) as salvage therapy after failure of
standard therapies including brentuximab vedotin (BV) in relapsed
or refractory (R/R) Hodgkin lymphoma (HL). Overall, the combination
was well-tolerated and the 3-month ORR of 83% (5/6) compares
favorably to historical ORR of pembrolizumab alone in a similar
patient population (58-63%).
"We are pleased with this early data from our
ongoing Phase 1b trial which demonstrate that AFM13 can safely be
administered in combination with Keytruda," said Dr. Adi Hoess, CEO
of Affimed. "Importantly, we also report promising ORR data in
patients which have failed prior treatments including ASCT and BV.
While we have reported encouraging monotherapy data from earlier
trials in the past showing that AFM13 is able to induce remission
in heavily pretreated lymphoma patients, we believe that the
combination with Keytruda has great potential to provide additional
benefit to patients. These data mark significant progress towards a
safe and effective NK cell engager-based cancer immunotherapy. With
the extension cohort accruing, we look forward to continuing on
this path."
Patients received escalating doses of AFM13 in
combination with pembrolizumab at a flat dose of 200 mg
administered every 3 weeks following the classical 3+3 design.
Recruitment now continues into an extension cohort at the highest
dose level explored during dose escalation. Response assessment is
performed every 12 weeks by PET/CT according to the Lugano
Classification Revised Staging System for malignant lymphoma.
Safety ResultsThree patients were enrolled into
dose levels 1 (0.5 mg/kg) and 2 (1.5 mg/kg),
respectively, and six patients were enrolled into dose level 3
(7.0 mg/kg). One dose-limiting toxicity (DLT) was observed in
cohort 3, which was a repeated grade 2 infusion-related reaction
(IRR), leading to discontinuation of AFM13 treatment. This event
classified as a DLT according to the protocol definition. No
additional DLTs occurred. The dose extension cohort has been
initiated with the highest dose explored during dose escalation
(7.0 mg/kg).
Most of the adverse events (AEs) observed were
mild to moderate in nature and were manageable with standard of
care. The most frequently observed AEs were IRRs (83%), nausea
(42%), diarrhea (33%), headache (33%), pyrexia (33%) and rash
(33%). Most of these events were of grade 1 or 2 severity.
There was a total of four grade 3 AEs observed in the study with
three events being deemed at least possibly related to both AFM13
and pembrolizumab: grade 3 IRR, grade 3 nausea and grade 3
vomiting. The remaining grade 3 AE of a duodenal ulcer was
assessed as not related to either study treatment. The
maximum-tolerated dose (MTD) was not reached.
Efficacy ResultsThree-month metabolic responses
were reported based on both local and independent assessment. By
local assessment, in cohort 1, two Partial Metabolic Responses
(PmRs) and one Progressive Metabolic Disease (PmD) were observed.
In cohort 2, one Complete Metabolic Response (CmR), one PmR and one
PmD were observed. In cohort 3, five PmRs and one PmD were observed
by both local and independent assessments. This ORR of 83% (5/6)
compared favorably to the historical ORR of pembrolizumab as
monotherapy in R/R HL patients who were post autologous stem cell
transplantation (ASCT) or ineligible for ASCT and have failed BV
(58-63%). Additionally, a deepening of response was reported where
a single case of PmR was converted into CmR at the 6-month
assessment (independent assessment). Based on the risk/benefit
analysis and recommendation by an independent data review committee
(DRC) the extension cohort is currently recruiting.
Poster InformationAnsell et al.: A Phase 1 Study
Investigating the Combination of AFM13 and the Monoclonal Anti-PD-1
Antibody Pembrolizumab in Patients with Relapsed/Refractory Hodgkin
Lymphoma after Brentuximab Vedotin Failure: Data from the Dose
Escalation Part of the Study (Abstract #1522)
AFM26 effectively induces killing of
multiple myeloma cells in vitro
In a second poster presentation, preclinical
data on AFM26, Affimed's B-cell maturation antigen
(BCMA)/CD16A-targeting antibody were reported. Standard of care in
first line treatment of multiple myeloma (MM) in eligible patients,
high dose melphalan combined with ASCT, fails to eradicate minimal
residual disease (MRD) in the majority of patients, ultimately
leading to disease relapse.
AFM26 is designed to address the significant
medical need of achieving sustained MRD negativity in MM by
selectively engaging NK cells to induce myeloma cell lysis through
its high-affinity bivalent binding to the key activating receptor
CD16A. Thus, AFM26 can be used to "arm" NK cells for effective
killing of myeloma cells.
Employing a wide range of functional assays, the
data presented at ASH corroborated earlier studies, demonstrating
that AFM26 induces autologous NK cell-mediated lysis of primary
myeloma cells in a manner strictly dependent on target cell
contact. In particular, AFM26 induces NK cell cytotoxicity towards
cells expressing very low surface levels of BCMA, suggesting the
potential for broad and deep anti-MM activity. Moreover, AFM26
binds with high affinity to NK cells in the presence of
patient-derived IgG1 paraprotein, confirming that AFM26 is less
prone to interference by high levels of circulating serum IgG
compared to Fc-based antibodies. In addition, AFM26 possesses
prolonged NK cell retention times and induces markedly lower levels
of pro-inflammatory cytokines in peripheral blood mononuclear cell
(PBMC) cultures in the presence of target cells compared to
BCMA-directed T cell-activating approaches. In contrast to other
monoclonal antibodies (mAbs) developed as MM therapies such as
daratumumab and elotuzumab, AFM26 does not confer
target-independent NK cell activation or NK cell depletion.
Due to their early reconstitution following ASCT
and their ability to rapidly destroy malignant cells through direct
cytotoxicity, NK cells are promising effector cells to target MRD
in this setting. AFM26's safety profile anticipated based on
preclinical data suggests suitability for enhancing the
cytotoxicity of endogenous NK cells as well as adoptively
transferred NK cells. Redirecting NK cells through AFM26 may
therefore offer an effective treatment option for MM patients early
after or in conjunction with ASCT. Thus, AFM26 is
well-differentiated from other mAbs and a promising therapeutic
candidate to address the unmet medical need of eradicating MRD in
MM.
Poster InformationGantke et al.: AFM26 -
Targeting B Cell Maturation Antigen (BCMA) for NK Cell-Mediated
Immunotherapy of Multiple Myeloma (Abstract #3082)
About Affimed's NK cell engagersAffimed has
developed a novel technology platform of NK cell-engaging
antibodies to overcome the ability of tumor cells to evade immune
recognition. Affimed's NK cell engagers are tetravalent (four
binding domains) and bispecific (targeting two cell types, NK and
tumor cell). Affimed has selected CD16A, a key activating receptor
as NK cell target, allowing for high affinity and high specificity
binding of target cells even with low target expression. Binding to
CD16A redirects NK cells to recognize the tumor cell, triggering a
signal cascade that leads to the destruction of tumor cells.
Affimed has developed a pipeline of preclinical and clinical
product candidates designed to address the medical need in
hematologic and solid tumors as mono- and combination
therapies.
About AFM13AFM13 is a first-in-class
tetravalent, bispecific NK cell engager that specifically binds to
CD30 on tumor cells and to CD16A on NK cells. AFM13 is being
developed in Hodgkin lymphoma (HL) and in other CD30-positive
lymphomas. AFM13 has shown a favorable safety profile and signs of
therapeutic efficacy in a monotherapy setting in studies in HL and
CD30+ lymphoma with cutaneous manifestation. In addition, early
data from a combination study of AFM13 with Merck's anti-PD1
antibody Keytruda® (pembrolizumab) supports proof of principle for
the combination of NK cell engagement with checkpoint
inhibition.
About AFM26AFM26 is a first-in-class
tetravalent bispecific NK cell engager that specifically binds to
B-cell maturation antigen (BCMA) on myeloma cells and to CD16A on
NK cells. AFM26 is being developed in multiple myeloma (MM) and
offers a differentiated mode of action, targeting cells expressing
very low levels of BCMA, conferring NK cell cytotoxicity without
depleting NK cells, eliciting lower cytokine release compared to T
cell-activating approaches and with NK cell binding largely
unaffected by IgG competition. These unique features could position
AFM26 in patients receiving autologous stem cell transplant (ASCT)
at or shortly after transplant, a period in which no treatment is
currently available. AFM6 is currently in preclinical
development.
About Affimed N.V.Affimed (Nasdaq: AFMD)
engineers targeted immunotherapies, seeking to cure patients by
harnessing the power of innate and adaptive immunity (NK and T
cells). We are developing single and combination therapies to treat
cancers and other life-threatening diseases. For more information,
please visit www.affimed.com.
FORWARD-LOOKING STATEMENTSThis
press release contains forward-looking statements. All statements
other than statements of historical fact are forward-looking
statements, which are often indicated by terms such as
"anticipate," "believe," "could," "estimate," "expect," "goal,"
"intend," "look forward to", "may," "plan," "potential," "predict,"
"project," "should," "will," "would" and similar expressions.
Forward-looking statements appear in a number of places throughout
this release and include statements regarding our intentions,
beliefs, projections, outlook, analyses and current expectations
concerning, among other things, our ongoing and planned preclinical
development and clinical trials, our collaborations and development
of our products in combination with other therapies, the timing of
and our ability to make regulatory filings and obtain and maintain
regulatory approvals for our product candidates our intellectual
property position, our collaboration activities, our ability to
develop commercial functions, expectations regarding clinical trial
data, our results of operations, cash needs, financial condition,
liquidity, prospects, future transactions, growth and strategies,
the industry in which we operate, the trends that may affect the
industry or us and the risks uncertainties and other factors
described under the heading "Risk Factors" in Affimed's filings
with the Securities and Exchange Commission. Given these risks,
uncertainties and other factors, you should not place undue
reliance on these forward-looking statements, and we assume no
obligation to update these forward-looking statements, even if new
information becomes available in the future.
Contact:Anca Alexandru, Head of
Communications, EU IRPhone: +49 6221 64793341E-Mail:
a.alexandru@affimed.com, IR@affimed.com
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