SPEAR T-cells Targeting MAGE-A4 Demonstrate New Responses in Esophagogastric Junction (EGJ), Lung, and Head and Neck Cancers ...
May 29 2020 - 7:30AM
Adaptimmune Therapeutics plc (Nasdaq:ADAP), a leader in cell
therapy to treat cancer, presented updated data from its ADP-A2M4
Phase 1 trial at the American Society for Clinical Oncology (ASCO)
Annual Meeting. The data demonstrate durability and responses in
synovial sarcoma, supporting SPEARHEAD-1 as a potential
registrational trial. The ASCO presentation also describes a new
response in a patient with lung cancer, and a response in a patient
with head and neck cancer (reported in January).
The Company also announced new responses in the SURPASS trial,
confirming the potential for SPEAR T‑cell therapies targeting
MAGE-A4 to treat a broad range of cancers in addition to sarcoma.
These data further support the rationale for two new Phase 2 trials
– SPEARHEAD-2 in head and neck cancer, which will begin later this
year, and a second trial in esophagogastric junction (EGJ) cancer
planned for 1H 2021. A webcast of Dr. Elliot Norry, Adaptimmune’s
Chief Medical Officer, and Adrian Rawcliffe, Adaptimmune’s Chief
Executive Officer, summarizing these and other clinical data is
available here: https://bit.ly/3enqBBy.
“I am pleased to announce that we have identified a new
indication to progress into late stage development. We plan to
initiate a Phase 2 trial in esophagogastric junction cancer in the
first half of 2021, with our next-generation ADP-A2M4CD8 SPEAR
T-cells. In addition, the ASCO data demonstrate promising
durability for ADP-A2M4 in sarcoma bolstering our ambition to have
our first marketed therapy in 2022,“ said Adrian Rawcliffe, CEO.
“I’m thrilled with the responses in a broad range of tumors with
our programs targeting MAGE-A4 and AFP. I am confident that we will
be able to identify more indications for late stage development as
more patients are treated in our trials.”
During an oral presentation at ASCO, Dr. David Hong of the MD
Anderson Cancer Center reported positive durability and efficacy
data in synovial sarcoma from the ADP-A2M4 Phase 1 trial. Based on
these data, the Company believes that SPEARHEAD-1 can support
registration for ADP-A2M4. These positive data also supported
removal of the futility analysis from SPEARHEAD-1, reducing the
sample size from 60 to 45 patients.
Outside of sarcoma, Dr. Hong shared a new RECIST response in a
patient with lung cancer, as well as the response in a patient with
head and neck cancer reported earlier this year. Further, he
reported evidence of anti-tumor activity in ovarian cancer, bladder
cancer, and melanoma.
In the SURPASS trial, three patients have responded out of the
first four treated with ADP-A2M4CD8. One patient with EGJ cancer
treated in the first dose cohort had a confirmed partial response
(PR) reported in January, which remains ongoing approximately six
months post-infusion. As reported today, a second patient in the
first dose cohort, also with EGJ cancer, has an unconfirmed PR. The
third response in the trial is an unconfirmed PR in a patient with
head and neck cancer. Data from this trial will be updated and
presented in the second half of 2020 at a medical conference. Based
on these data, the Company plans to initiate a Phase 2 trial in EGJ
cancer in the first half of 2021.
In January, the Company reported one confirmed PR in a patient
with liver cancer from the ADP‑A2AFP Phase 1 trial. Subsequently,
this PR has been assessed as a confirmed complete response, which
remained ongoing at the last assessment (Week 24). The next two
patients with liver cancer (or hepatocellular carcinoma [HCC])
treated in Cohort 3 did not respond. A separate cohort for AFP
expressing tumors other than HCC was initiated and the one patient
treated to date has not responded. Detailed data will be presented
in a poster and an oral presentation at the International Liver
Congress (ILC) in August 2020 (rescheduled from April of this
year).
RECIST Responses with SPEAR T-cell Monotherapy in
Patients with Late Stage Cancers*
Indication |
Responses/(n) a |
SPEAR T-cell Target |
SPEAR T-cell product demonstrating responses |
New response reported today |
Synovial sarcoma |
8 PR b / 16 |
MAGE-A4 |
ADP-A2M4 |
Yes |
Head and neck |
2 PR b / 4 |
MAGE-A4 |
ADP-A2M4/ ADP-A2M4CD8 |
Yes |
EGJ |
2 PR b / 3 |
MAGE-A4 |
ADP-A2M4CD8 |
Yes |
Lung |
1 PR / 2 |
MAGE-A4 |
ADP-A2M4 |
Yes |
Melanoma |
1 PR c / 2 |
MAGE-A4 |
ADP-A2M4 |
No |
Liver (HCC) |
1 CR d / 3 |
AFP |
ADP-A2AFP |
No |
a: n=number of patients treated; b: includes one unconfirmed PR;
c: patient treated in radiation sub-study of ADP‑A2M4 Phase 1
trial; d: previously assessed as PRCR=complete response;
EGJ=esophagogastric junction; HCC=hepatocellular carcinoma;
PR=partial response* As of May 2020
ADP-A2M4 clinical update
- ASCO: Oral presentation by Dr. David Hong
titled: “Phase 1 Dose Escalation and Expansion Trial to Assess
Safety and Efficacy of ADP-A2M4 in Advanced Solid Tumors”
- Synovial sarcoma data
- 50% response rate with inclusion of unconfirmed PR
assessed after data cut-off (44% response rate without inclusion of
unconfirmed PR)
- Median duration of response ~28 weeks, progression free
survival ~20 weeks, median overall survival not reached
- 3 out of the 7 responders have continued to benefit as of their
one year assessments
- Disease control rate of 90% defined by best overall response
(BOR) of PR or stable disease (SD) at time of data cut off (April
6, 2020)
- Other cancer indications
- Confirmed responses in lung cancer (reported today) and head
& neck cancer (as reported in January)
- Of note, there was a response in a patient with rectal mucosal
melanoma from the radiation sub-study of this trial (still
recruiting) reported in January, which remains ongoing at Week 24.
This patient was not part of the ASCO dataset
- Most adverse events were consistent with those typically
experienced by cancer patients undergoing lymphodepletion cytotoxic
chemotherapy, and cellular therapy
- Trial closed for enrollment with the exception of ongoing
recruitment in the low-radiation sub-study
- SPEARHEAD-1
- Intended to be a registrational trial
- Based on the strength of the ADP-A2M4 Phase 1 data, futility
analysis removed reducing the sample size from 60 to 45
patients
- Recruiting patients in 20 centers in Canada, France, Spain, and
the US
- Screened more than half the patients likely required to
complete the trial
- Currently, there are more than 30 patients identified who would
be eligible based on HLA and MAGE-A4 expression
- Aim to complete SPEARHEAD-1 recruitment by 1H 2021 and launch
in the US in 2022
Other trials in the MAGE-A4 program
SURPASS
- Out of the first 4 patients treated (2 with EGJ cancer; 1 with
ovarian cancer, 1 with head and neck cancer) 3 have been assessed
as PRs (1 confirmed)
- 2 patients with EGJ cancer (1 confirmed PR announced in January
and a second unconfirmed PR announced today)
- 1 patient with head and neck cancer with an unconfirmed PR
- Based on the responses in EGJ cancer, the Company plans to
initiate a new Phase 2 trial in this indication
- Planning to present the full trial design in 2H 2020 and to
initiate the trial in 1H 2021
- Enrollment in the SURPASS trial will focus on indications for
which there have been early signs of efficacy, including responses,
with SPEAR T-cells targeting MAGE-A4. These indications include
lung, EGJ, head & neck, and bladder cancers
- Cohorts 2 and 3 were merged and 3 patients will be treated in
this new group with up to 5 billion SPEAR T-cells, before moving
into the expansion phase (subject to safety)
- Data will be presented at an upcoming medical oncology congress
in 2H 2020
SPEARHEAD-2
- The trial will enroll 10 patients with head and neck cancer
combining ADP-A2M4 with pembrolizumab following initiation of first
line pembrolizumab in the relapsed/metastatic setting
- This will be the first time that a SPEAR T-cell will be used in
sequence with first line systemic therapy
- All patients will be apheresed and have their cells
manufactured with the intent of having their SPEAR T-cells
available by the time of their first assessment on
pembrolizumab
- Patients who do not respond to pembrolizumab (published
response rate ~20%) or who progress after an initial response will
receive SPEAR T-cells and continue to receive pembrolizumab
- All clinical sites are in the process of being initiated
ADP-A2AFP clinical trial
- There is one confirmed complete response, reported in January
as a PR, in a patient with liver cancer – the first patient treated
at target dose in Cohort 3
- The next two patients in this cohort did not respond
- Following requests from investigators, the Company opened a
cohort for patients with non-hepatocellular carcinoma tumors that
express AFP and the one patient treated in this cohort has also not
responded
- Data will be presented at the International Liver Congress in
August
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 May 14, 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.
Adaptimmune Contacts:
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
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