Adaptimmune Reports Positive Results from its Pivotal SPEARHEAD-1 Trial in Patients with Synovial Sarcoma and MRCLS at CTOS
12 November 2021 - 1:00AM
Adaptimmune Therapeutics plc (Nasdaq:ADAP), a leader in cell
therapy to treat cancer, will report updated clinical and
translational data from its pivotal SPEARHEAD-1 trial with
afamitresgene autoleucel (afami-cel, formerly ADP-A2M4) in patients
with advanced synovial sarcoma or myxoid/round cell liposarcoma
(MRCLS) at the Connective Tissue Oncology Society (CTOS)
annual meeting.
“The positive results presented at CTOS further validate the
potential of this therapy to address a great unmet medical need for
patients with synovial sarcoma and MRCLS,” said Elliot Norry,
Adaptimmune’s Chief Medical Officer. “We are confident that these
data will support our BLA filing for afami-cel next year.”
“Afami-cel would provide a new treatment option for patients
with synovial sarcoma, offering benefits that we have rarely seen
with therapies currently available for this patient population,”
said Dr. Brian A. Van Tine, Professor of Medicine and of Pediatrics
at Washington University School of Medicine in St. Louis. “This is
a game changer for patients with a high unmet medical need.”
Clinical data will be presented in an oral presentation by Dr.
Brian Van Tine of the Washington University School of Medicine in
St. Louis (Abstract #1080870) during the Immunotherapy & Immune
Microenvironment Session starting at 10:00 a.m. EST on November
12th.
Preliminary translational insights from the Phase 2 SPEARHEAD-1
trial will also be presented in a poster (Abstract #1080366) by Dr.
Sandra P. D’Angelo of Memorial Sloan Kettering Cancer Center during
the Immunology & Immunotherapy Session beginning at 2:30 p.m.
EST on November 12th.
Efficacy data validate the meaningful clinical benefit
of afami-cel (data cut-off September 1, 2021)
- 50 patients had received afami-cel (42 with synovial sarcoma, 8
with MRCLS)
- Median age of patients was 41 years (range: 19 to 73) and they
had received a median of three prior lines of therapy (range: 1 to
12)
- The median dose was 8.5 billion transduced SPEAR T-cells
(range: 2.7 to 10)
- Three patients had scans awaiting Independent Review and 47
patients were evaluable
- The primary endpoint for SPEARHEAD-1 is response according to
RECIST v1.1 evaluated by Independent Review 1
- Based on the reported overall response rate, the trial will
meet its primary endpoint in the final analysis planned later this
year
- Per Independent Review, the overall response rate was 34%
(16/47 patients with partial responses [PRs])
- The overall response rate was 36% in patients with synovial
sarcoma, and 25% for patients with MRCLS
- The disease control rate (defined as stable disease, PR, or CR)
was 85% per Independent Review
- The overall response rate and disease control rate per
Independent Review were comparable to the assessments by
Investigator Review (34% and 84%, respectively)
- Durability is encouraging and the median duration of response
has not been reached
- 75% of patients with response remain ongoing and the duration
ranged from 4.3+ to 65.3+ weeks
Afami-cel was well-tolerated and has a
favorable benefit:risk profile as of data cut-off
- Thirty-three (66%) patients experienced adverse events of
cytokine release syndrome (CRS), most of which were lower grade:
Grade 1 or 2 (n=32); Grade 3 (n=1)
- The most common serious adverse event (SAE) of any grade was
CRS reported in 6% of patients
- Eight (16%) patients experienced ≥ Grade 3 cytopenia at Week
4
Emerging translational data support clinical benefit
seen in patients with afami-cel
- Afami-cel SPEAR T-cells successfully engrafted in all patients
and maintained high levels of persistence in most patients followed
for at least 6 months post-infusion
- CD8+ SPEAR T-cells in drug products administered killed >70%
tumor cells in vitro
- Serum cytokine response profile indicates an IFNγ-driven
mechanism of action, signaling an afami-cel induced immune
response
- Clinical benefit seen across a broad range of MAGE-A4
expression
- Post-infusion biopsies indicated that infiltrating afami-cel
SPEAR T-cells co-localize with tumor and additional immune cells,
with evidence of activated and proliferative state and
adaptive-immune response
Conclusion from the Phase 2 SPEARHEAD-1
trial
- The trial will meet its primary endpoint for efficacy for this
pivotal trial
- As of September 1, 2021, overall response rate was 34% with a
disease control rate of 85% per Independent Review in 47 heavily
pre-treated patients
- Durability of responses is encouraging, and the median duration
of response has not been reached
- The benefit:risk profile of afami-cel has been favorable, with
mainly low-grade CRS and tolerable/reversible hematologic
toxicities
- Translational data confirm that afami-cel is active against
MAGE-A4 expressing targets both in vitro and in vivo
- These data will be used to support Adaptimmune’s Biologics
License Application (BLA) submission next year
Overview of SPEARHEAD-1 trial designSPEARHEAD-1
is a Phase 2, open-label trial for people with advanced synovial
sarcoma or MRCLS to evaluate the efficacy, safety, and tolerability
of afami-cel. Afami-cel SPEAR T-cells target MAGE-A4+ tumors.
MAGE-A4 is highly expressed in synovial sarcoma and MRCLS in the
context of HLA-A*02. Compelling clinical responses in patients with
synovial sarcoma were previously reported with afami-cel in a Phase
1 trial (CTOS 2020).
Approximately 90 patients are planned to be treated: 45 in
Cohort 1 and 45 in Cohort 2. Enrollment in Cohort 1 is complete,
and Cohort 2 is currently recruiting. The primary efficacy analysis
will be for Cohort 1 only, which will be used to support the BLA
filing next year. No formal hypothesis testing is planned for
Cohort 2. Cohort 2 will strengthen the efficacy and safety database
and will aid in descriptive sub-group analyses.
Key eligibility criteria: ECOG performance status of 0 or 1;
HLA*02 positive with MAGE-A4 expression in ≥ 30% of tumor cells ≥
2+ by immunohistochemistry; aged ≥ 16 and ≤ 75 years; and
patients must have received either an anthracycline- or
ifosfamide-containing regimen. Eligible patients received afami-cel
doses between 1–10 × 109 transduced T-cells after receiving
lymphodepleting chemotherapy.
About Adaptimmune Adaptimmune 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 Statements This 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 Securities and Exchange Commission
(SEC) on November 4, 2021, 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, Corporate
Affairs and Communications T: +44 1235 430 583 M: +44
7718 453 176 Sebastien.Desprez@adaptimmune.com
Investor Relations: Juli P. Miller, Ph.D.
— VP, Investor Relations T: +1 215 825 9310 M: +1
215 460 8920 Juli.Miller@adaptimmune.com
1 The primary endpoint will be evaluated using a one-sided
exact-based Clopper-Pearson 97.5% confidence interval (CI). If the
lower bound of the CI exceeds the response rate reported with
historical second line therapy(ies) (18%), the trial will have met
the pre-specified threshold for demonstrating efficacy.
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