- 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
- 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)
- 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 design
SPEARHEAD-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 × 10 9 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.
