RAPT Therapeutics, Inc. (Nasdaq: RAPT), a clinical-stage,
immunology-based biopharmaceutical company focused on
discovering, developing and commercializing oral small molecule
therapies for patients with significant unmet needs in oncology and
inflammatory diseases, today announced positive initial clinical
data from its ongoing Phase 1/2 trial for FLX475 in multiple cancer
indications.
Initial observations as of November 10, 2020 from the ongoing
trial for FLX475 include preliminary:
- evidence of monotherapy
activity,
- encouraging efficacy in combination
with the PD-1 checkpoint inhibitor pembrolizumab (marketed as
Keytruda®) and
- biomarker data supporting FLX475’s
mechanism of action.
In addition, FLX475 demonstrated a favorable safety profile,
both as monotherapy and in combination with pembrolizumab.
“We are pleased with the early evidence of clinical activity of
FLX475, both as monotherapy and in combination with pembrolizumab
in multiple charged tumor types,” said Brian Wong, M.D., Ph.D.,
President and CEO of RAPT. “Based on these encouraging data, we
have determined that three cancer indications, EBV+ lymphoma,
nasopharyngeal cancer and head and neck cancer, have generated
sufficient early evidence of efficacy to advance into expanded
Phase 2 evaluation. We continue to enroll patients and generate
data in this multi-cohort, multi-indication trial and look forward
to providing updates on all remaining cohorts and additional
go-forward decisions next year.”
Scott Antonia, M.D., PhD., Professor of Medicine and Director of
the Duke Cancer Institute Center for Cancer Immunotherapy and a
member of RAPT’s Scientific Advisory Board, added, “FLX475 is a
potent non-depleting CCR4 antagonist that is designed to block
regulatory T cells that interfere with an effective anti-tumor
immune response. These data are particularly impressive as the
immunotherapy field has long recognized Treg as important targets
in oncology, but until FLX475, others have not been able to
selectively target these cells in the tumor microenvironment
without affecting beneficial cells. These data demonstrate
that RAPT’s oral small molecule approach with FLX475 holds promise
in treating a variety of charged cancers.”
Charged cancers are tumors that contain high levels of both
regulatory T cells (Treg) and CD8 T cells and express high levels
of the ligands for CCR4.
Phase 1/2 Clinical Trial
DesignThe ongoing open-label Phase 1/2 study is
enrolling patients with multiple types of cancer at leading cancer
centers across the United States, Australia and Asia. The Phase 1
portion of the trial is focused on evaluating the safety,
pharmacokinetics and pharmacodynamics of FLX475 as a monotherapy
and in combination with pembrolizumab. The Phase 2 portion is
designed to evaluate the degree of antitumor activity of FLX475 as
a monotherapy and in combination with pembrolizumab specifically in
patients with several types of charged tumors. Changes in the tumor
microenvironment and other biomarkers are being evaluated in both
phases of the study. For more information please visit
clinicaltrials.gov identifier NCT03674567.
Phase 1 Dose Escalation
DataThe dose escalation Phase 1 portion of the
trial enrolled a total of 37 patients with cancers of different
types. Nineteen patients were treated with one of four doses (25
mg, 50 mg, 75 mg or 100 mg once daily) of FLX475 monotherapy and 18
were treated with one of three doses (50 mg, 75 mg or 100 mg once
daily) of FLX475 in combination with the standard dose of
pembrolizumab. Disease control, defined as a best response of
stable disease (SD), an unconfirmed or confirmed partial response
(PR) or complete response (CR), was observed in 14 of the 17
evaluable monotherapy patients, including an unconfirmed partial
response in a patient with relapsed metastatic cervical cancer. In
the combination cohorts, disease control was observed in 13 of the
14 evaluable patients. This includes two confirmed partial
responses: a patient with NSCLC who had progressed on prior
checkpoint treatment (atezolizumab) and who remains on study after
18 months of treatment, and a patient with checkpoint
inhibitor-naïve urothelial cancer who was on study for over nine
months of treatment. In addition, preliminary data show an increase
in the CD8 to Treg ratio after treatment, which is consistent with
the hypothesis that a CCR4 antagonist can block the recruitment of
tumor Treg, increase the CD8 to Treg ratio and potentially enhance
antitumor immunity.
The Phase 1 results also show FLX475 had a favorable safety
profile, with no maximum tolerated dose reached. Two dose-limiting
toxicities (DLTs) of asymptomatic QTc prolongation were observed in
the monotherapy cohorts, one in the 75 mg cohort and one in the 100
mg cohort. No DLTs were observed in the Phase 1 combination
cohorts. Based on the Phase 1 data, 100 mg was selected as the
recommended Phase 2 dose for both the monotherapy and combination
therapy cohorts.
Phase 2 DataThe ongoing
Phase 2 portion of the trial is enrolling a minimum of 80
patients with several types of charged tumors, 10 in each of eight
cohorts, with four cohorts evaluating FLX475 as a monotherapy and
four cohorts evaluating FLX475 in combination with pembrolizumab.
The charged cancers include Epstein-Barr Virus (EBV)- or Human
Papillomavirus (HPV)-associated cancers such as nasopharyngeal
cancer, cervical cancer, and subsets of Hodgkin and non-Hodgkin
lymphomas as well as head and neck cancer. Other charged tumor
types include non-small cell lung cancer and triple-negative breast
cancer. The protocol calls for expansion of cohorts to generate
additional data based on promising clinical activity.
Based on the promising early results from the Phase 1/2 trial
with FLX475 observed to date, RAPT has selected three cancer
indications for expansion:
- EBV+ lymphoma – Early data from the
first two patients with EBV+ lymphoma treated with FLX475
monotherapy show significant target tumor reduction, including one
patient (1/2) who achieved a durable complete metabolic response
and continues on study after more than nine months. RAPT plans to
expand the EBV+ lymphoma monotherapy cohort and initiate a separate
expansion cohort in EBV+ lymphoma in combination with
pembrolizumab.
- Checkpoint inhibitor-naïve
nasopharyngeal cancer (NPC) – Of the 10 evaluable patients with NPC
treated with FLX475 monotherapy, seven of 10 (7/10) patients
exhibited stable disease as best response. Seven of the 10 patients
crossed over to combination therapy where significant clinical
activity has been observed. Of the six evaluable patients who
crossed over, five were checkpoint inhibitor naïve. All five (5/5)
of the checkpoint inhibitor-naïve patients demonstrated significant
tumor shrinkage, with three (3/5) of these patients showing a
partial response (two confirmed and one unconfirmed). Based on
these results, RAPT plans to open a combination cohort in
checkpoint inhibitor-naïve NPC.
- Checkpoint inhibitor-naïve head and
neck cancer – Of the 10 evaluable patients with head and neck
cancers treated with FLX475 monotherapy, five of 10 (5/10) patients
exhibited stable disease as best response. Six patients initially
treated with monotherapy crossed over to combination therapy, with
one achieving a partial response and a second patient with an
unconfirmed partial response (2/6). Seventeen patients are enrolled
in a separate combination treatment cohort, of which 10 are
evaluable so far. Substantial tumor reduction has been observed in
four of the 10 (4/10), including one confirmed complete response
and three patients with greater than 20 percent tumor reduction.
Based on these results, RAPT plans to expand the combination cohort
in checkpoint inhibitor-naïve head and neck cancers.
In these Phase 2 cohorts, FLX475 demonstrated a favorable safety
profile with once-daily oral dosing both as monotherapy and in
combination with pembrolizumab.
Phase 2 Stage 1 Cohortsa |
Evaluable (N) |
ORR (%)b |
DCR (%)c |
EBV+ lymphoma monotherapy |
2 |
50% |
50% |
Nasopharyngeal monotherapy |
10 |
- |
70% |
Nasopharyngeal (CPI-naïve) crossover |
5 |
60% |
100% |
Head and Neck (CPI-naïve) monotherapy |
10 |
- |
50% |
Head and Neck (CPI-naïve) crossover |
6 |
33% |
66% |
Head and Neck (CPI-naïve) combination |
10 |
10% |
60% |
a Interim data as of November 10, 2020 from the ongoing
FLX475-02 Phase 1/2 study; data subject to change.bORR = objective
response rate defined as unconfirmed and confirmed PR or CRcDCR =
disease control rate defined as unconfirmed and confirmed PR or CR
and SD as best response
Conference Call InformationThe Company will
host a webcast conference call accompanied by a slide presentation
to discuss initial data from the Phase 1/2 study of FLX475 today at
8:30 a.m. Eastern Time. The call can be accessed by dialing (833)
672-0665 (domestic) or (929) 517-0344 (international) and refer to
conference ID 6772479. The webcast will be available for replay for
two weeks.
About FLX475 FLX475 is a small molecule CCR4
antagonist designed to block the migration of regulatory T cells
(Treg) specifically into tumors, but not healthy tissues.
Treg represent a dominant pathway for downregulating the
immune response, generally correlate with poor clinical outcomes
and may limit the effectiveness of currently available therapies
such as checkpoint inhibitors. RAPT is developing FLX475 for the
treatment of a broad range of “charged” tumors, which represent
cancer types the Company believes are most likely to respond to
FLX475, where a large quantity of Treg cells are likely to be
the cause of immune suppression within the tumor. FLX475 may
restore naturally occurring antitumor immunity alone and may
synergize with a variety of both conventional and immune-based
therapies, such as radiation, chemotherapy, checkpoint inhibitors,
immune stimulators, cancer vaccines and adoptive T cell
therapy.
About RAPT Therapeutics, Inc.RAPT
Therapeutics is a clinical stage immunology-based biopharmaceutical
company focused on discovering, developing and commercializing oral
small molecule therapies for patients with significant unmet needs
in oncology and inflammatory diseases. Utilizing its proprietary
discovery and development engine, the Company is developing highly
selective small molecules designed to modulate the critical immune
drivers underlying these diseases. RAPT has discovered and advanced
two unique drug candidates, FLX475 and RPT193, each targeting C-C
motif chemokine receptor 4 (CCR4), for the treatment of cancer and
inflammation, respectively. The Company is also pursuing a range of
targets, including hematopoietic progenitor kinase 1 (HPK1) and
general control nonderepressible 2 (GCN2), that are in the
discovery stage of development.
Forward-Looking StatementsThis press release
contains forward-looking statements. These statements relate to
future events and involve known and unknown risks, uncertainties
and other factors that may cause our actual results, performance or
achievements to be materially different from any future
performances or achievements expressed or implied by the
forward-looking statements. Each of these statements is based only
on current information, assumptions and expectations that are
inherently subject to change and involve a number of risks and
uncertainties. Forward-looking statements include, but are not
limited to, statements about clinical development progress, the
significance of early results from Phase 1/2 clinical trials of
FLX475 and plans with respect to Phase 2 expansions. Detailed
information regarding risk factors that may cause actual results to
differ materially from the results expressed or implied by
statements in this press release may be found in RAPT’s most recent
Form 10-Q filed with the Securities and Exchange Commission and
subsequent filings made by RAPT with the Securities and Exchange
Commission. These forward-looking statements speak only as of the
date hereof. RAPT disclaims any obligation to update these
forward-looking statements.
RAPT Media Contact:Angela
Bittingmedia@rapt.com(925) 202-6211
RAPT Investor Contact:Sylvia
Wheelerswheeler@wheelhouselsa.com
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