Adaptimmune Therapeutics plc (Nasdaq: ADAP), a leader in cell
therapy to treat cancer, presented data from the dose escalation
cohorts of its Phase 1 SURPASS trial using ADP-A2M4CD8 in a poster
at the Society for the Immunotherapy of Cancer (“SITC”) Conference.
In these cohorts of heavily pre-treated patients with advanced
cancers (n=6), three were treated with target doses of
1 billion SPEAR T-cells, and three with target doses of 5
billion. Most adverse events were consistent with those typically
experienced by cancer patients undergoing cytotoxic chemotherapy or
cancer immunotherapy.
“We have seen responses in two out of six patients treated in
the safety cohorts of the SURPASS trial as well as antitumor
activity in five of them. The responses and antitumor activity we
have seen with our next-generation ADP-A2M4CD8 SPEAR T-cells,
across a range of solid tumors, support our belief that this is a
highly active product,” said Ad Rawcliffe, Adaptimmune’s Chief
Executive Officer. “Based on these data, we will initiate the Phase
2 trial in gastroesophageal cancers in the first half of 2021 and
look forward to identifying additional indications to take into
late-stage development.”
There were two confirmed partial responses (PRs): one in a
patient with esophagogastric junction (EGJ) cancer, previously
reported, and one in a patient with head and neck cancer, reported
as unconfirmed in May. The four other patients had best overall
responses of stable disease (SD). Overall, five out of six patients
treated had initial tumor shrinkage.
In vitro translational data using the manufactured products from
patients in the SURPASS trial indicate that co-expression of the
CD8α co-receptor on CD4+ ADP-A2M4 SPEAR T-cells enables them to
kill MAGE-A4 expressing target cells with equal potency as CD8+
SPEAR T-cells targeting MAGE-A4. These data, combined with the
responses and antitumor activity observed at low doses, indicate
that ADPA2M4D8 may be a more potent product than the
first-generation ADPA2M4 SPEAR T-cells.
Best Overall Response (BOR) and maximum changes from baseline in
target lesions in Cohorts 1 and 2
Indication |
Dose x 109 |
BOR |
Tumor reduction |
Head and neck |
4.6 |
PR |
-63.16% |
EGJ |
1.2 |
PR |
-51.52% |
EGJ |
1.0 |
SD |
-34.07% |
Ovarian |
1.1 |
SD |
-16.13% |
Esophageal |
6.0 |
SD |
-13.37% |
MRCLS |
5.7 |
SD |
+1.35% |
As of data cut-off: October 1, 2020
At SITC, Adaptimmune also presented a poster entitled
“Inhibition of AKT signaling during expansion of TCR-engineered
T-cells from patient leukocyte material generates SPEAR T-cells
with enhanced functional potential in vitro.” These preclinical
data indicate that AKT inhibition during the manufacture of SPEAR
T-cells results in a more consistent expansion and phenotype of the
final product. This process is currently being used for manufacture
of ADP-A2M4CD8 for the SURPASS trial.
The Company also presented two posters summarizing data for the
two completed Phase 1 trials with ADP-A2M10 (a previously
terminated program).
About AdaptimmuneAdaptimmune is a
clinical-stage biopharmaceutical company focused on the development
of novel cancer immunotherapy products for people with cancer. The
Company’s unique SPEAR® (Specific Peptide Enhanced Affinity
Receptor) T-cell platform enables the engineering of T-cells to
target and destroy cancer across multiple solid tumors.
Forward-Looking StatementsThis release contains
“forward-looking statements” within the meaning of the Private
Securities Litigation Reform Act of 1995 (PSLRA). These
forward-looking statements involve certain risks and uncertainties.
Such risks and uncertainties could cause our actual results to
differ materially from those indicated by such forward-looking
statements, and include, without limitation: the success, cost and
timing of our product development activities and clinical trials
and our ability to successfully advance our TCR therapeutic
candidates through the regulatory and commercialization processes.
For a further description of the risks and uncertainties that could
cause our actual results to differ materially from those expressed
in these forward-looking statements, as well as risks relating to
our business in general, we refer you to our Quarterly Report on
Form 10-Q filed with the SEC on November 5, 2020, and our other SEC
filings. The forward-looking statements contained in this press
release speak only as of the date the statements were made and we
do not undertake any obligation to update such forward-looking
statements to reflect subsequent events or
circumstances.
Media Relations:
Sébastien Desprez — VP, Communications and Investor RelationsT:
+44 1235 430 583M: +44 7718 453
176Sebastien.Desprez@adaptimmune.com
Investor Relations:
Juli P. Miller, Ph.D. — Senior Director, Investor RelationsT: +1
215 825 9310M: +1 215 460 8920Juli.Miller@adaptimmune.com
SITC Abstract
Title: Initial safety, efficacy, and product
attributes from the SURPASS trial with ADPA2M4CD8, a SPEAR T-cell
therapy incorporating an affinity optimized TCR targeting MAGE-A4
and a CD8α co-receptor
Authors: David S. Hong1, Jeffrey Clarke2,
Tanner Johanns3, Partow Kebriaei1, John V. Heymach1,
Ahmed Galal2, Samuel D. Saibil4, Adrian Sacher4, Francine E.
Brophy5, Gareth Betts6, Natalie Bath6, Will Spinner6,
Alex Tipping6, Jessica Tucci5, Raymond Luke5,
Trupti Trivedi5, Quan Lin5, JeanMarc Navenot5,
Paula M. Fracasso5, Karen Miller6, Elliot Norry5,
Mark Dudley5, Marcus O. Butler4
Affiliations
(Institution,
City, State,
Country):
1The University of Texas MD Anderson Cancer Center, Houston, TX,
United States of America, 2Duke Cancer Center, Durham, NC, United
States of America, 3Washington University School of Medicine, St.
Louis, MO, United States of America,4Princess Margaret Cancer
Centre, Toronto, Ontario, Canada, 5Adaptimmune, Philadelphia, PA,
United States of America, 6Adaptimmune, Abingdon, United
Kingdom
Abstract Body:
Background: The ongoing SURPASS trial
(NCT04044859) evaluates safety and efficacy of next-generation
ADP-A2M4CD8 SPEAR T-cells co-expressing the CD8α co-receptor with
the engineered MAGE-A4c1032 Tcell receptor (TCR).
Methods: First-in-human trial in HLA-A*02
positive patients (pts) with advanced cancers expressing MAGE-A4
antigen by immunohistochemistry. Eligible pts undergo apheresis,
Tcells are isolated, transduced with a Lentiviral vector containing
the MAGE-A4c1032 TCR and CD8α coreceptor, and expanded. Expansion,
transduction level, cellular composition and function of the
manufactured product (MP) are assessed in vitro. Prior to infusion,
pts receive lymphodepletion with fludarabine 30 mg/m2/day for
4 days and cyclophosphamide 600 mg/m2/day for 3 days.
Results: As of 16 July 2020, 5 pts
(1 with MRCLS, 2 with esophagogastric junction [EGJ] cancers, 1
with ovarian cancer, and 1 with head and neck cancer) were
treated with ADP-A2M4 CD8 (range ~1 to 5.7 billion transduced
cells). No DLTs or SAEs have been reported. To date, 1 pt with EGJ
cancer had a partial response (PR per RECIST) and has had
progression-free survival >6 months. One pt with head and neck
cancer also had a PR. All other pts have had best overall response
of stable disease.
MP expanded by an average of 15.3fold during manufacturing
(range 5.9 to 25.6-fold). On average, 43% of Tcells in the MP
expressed the TCR (range 23 to 63%). The fraction of CD4+ cells in
the final MP varied (range 45 to 84%). Coexpression of the MAGE-A4
TCR and CD8α in CD4+ T-cells in the patient MP enabled CD4+ T-cells
to kill tumor target cells directly in vitro. MAGE-A4 expression in
tumor biopsies varied (H-score range 55 to 300). Transduced T-cells
were detected in peripheral blood of all pts. IFNgamma increased
transiently in the serum of 1 pt who responded.
Conclusions: ADP-A2M4CD8 SPEAR T-cells have
shown an acceptable safety profile and pts with EGJ cancer and head
and neck cancer have demonstrated evidence of antitumor activity.
Translational data and early clinical results indicate that
co-expression of the CD8α co-receptor on CD4+ SPEAR T-cells may
increase the potency of the product by conferring additional
killing activity to the helper T-cell subset. This dose escalation
trial is ongoing and updated clinical and translational data will
be presented.
Adaptimmune Therapeutics (NASDAQ:ADAP)
Historical Stock Chart
From Aug 2024 to Sep 2024
Adaptimmune Therapeutics (NASDAQ:ADAP)
Historical Stock Chart
From Sep 2023 to Sep 2024