On November 11, 2021 Adaptimmune Therapeutics plc (Nasdaq:ADAP), a leader in cell therapy to treat cancer, reported that it 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 (Press release, Adaptimmune, NOV 11, 2021, View Source [SID1234595287]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"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 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 × 109 transduced T-cells after receiving lymphodepleting chemotherapy.