On May 6, 2019 Adaptimmune Therapeutics plc (Nasdaq:ADAP), a leader in T-cell therapy to treat cancer, reported significant clinical progress with partial responses in 4 out of 5 synovial sarcoma patients treated with ~10 billion cells in the ADP-A2M4 pilot study, and tumor shrinkage seen in nearly all assessed synovial sarcoma patients (Press release, Adaptimmune, MAY 6, 2019, View Source;p=RssLanding&cat=news&id=2397170 [SID1234535732]). Based on these data, the Company will initiate the SPEARHEAD-1 trial in patients with synovial sarcoma and myxoid/round cell liposarcoma (MRCLS) later this year.
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Beyond sarcoma, there is evidence of antitumor activity with ADP-A2M4 and ADP-A2M10 in other solid tumors. Based on these data and translational findings, the Company is expanding its clinical trial program by initiating a radiation sub-study, as well as opening a next-generation ADP-A2M4CD8 study (SURPASS trial), for which the IND has been filed. Finally, the first patient with HCC was treated in Cohort 2 (1 billion SPEAR T-cells) of the ADP‑A2AFP study and showed good tolerability to treatment and a transient decrease in serum AFP as well as tumor shrinkage at first scan.
"Today is a watershed moment for the Company. We now have confirmed responses in an unmet medical indication, synovial sarcoma, with our wholly owned ADP-A2M4 SPEAR T-cells. As we prepare to start the SPEARHEAD-1 study, we are one step closer to realizing our ambition to be the first T-cell company with an approved therapy in solid tumors in 2022," said James Noble, Adaptimmune’s Chief Executive Officer. "There is also early evidence of activity in other solid tumors with all three products and I am delighted to announce that we have filed an IND for a more potent, next-generation program with MAGE-A4 as the target. Working with world-class clinical trial centers and having a robust manufacturing and supply capability, we look forward to making further progress across the entire portfolio in the coming months."
ADP-A2M4 responses and data in synovial sarcoma patients
10 patients treated
8 patients assessed, with 6 showing tumor shrinkage
3 confirmed partial responses, 1 unconfirmed partial response
3 stable diseases (SD) and 1 progressive disease (PD)
ADP-A2M4 SPEAR T-cells appear to show a favorable benefit:risk profile in patients with synovial sarcoma
Good tolerability overall. Most adverse events are consistent with those typically experienced by cancer patients undergoing cytotoxic chemotherapy or other cancer immunotherapies
SPEARHEAD‑1 protocol summary
Single-arm, Phase 2 study in more than 20 centers (North America & Europe) to include 60 patients with:
Advanced (metastatic or inoperable) synovial sarcoma or MRCLS patients who have received prior chemotherapy
HLA-A*02 & MAGE-A4 antigen positive
MAGE-A4 expression 30% (2+, 3+)
Primary endpoint will be overall response rate by RECIST v1.1 by independent review
Interim futility: 3 or more responses in the first 15 patients for study continuation
Safety endpoints with Independent Data Safety Monitoring Board
Exploratory endpoints with translational data and patient-reported outcomes
Treatment
Lymphodepletion: Flu: (30 mg/m2/ day) x 4 days; Cy (1800 mg/ m2/ day) x 2 days
Dose: up to 10 billion transduced SPEAR T-cells
Antitumor activity in other indications with ADP-A2M4 and ADP-A2M10
Tumor shrinkage seen in lung patients (ADP-A2M10), and melanoma and ovarian patients (ADP-A2M4)
7 patients treated with ADP-A2M4 in indications other than sarcoma in Cohorts 3 and Expansion phase
3 SDs, 3 PDs, and 1 patient expired due to disease progression before the first scan
7 patients treated with ADP-A2M10 in Cohort 3 and Expansion phase in the NSCLC and triple tumor studies
4 SDs, with one patient receiving a second infusion at Week 16, and 3 PDs to date
Adaptimmune continues to examine patient data to gain a clearer understanding of the best path forward to enhance RECIST responses
Adaptimmune is planning to start two new studies to transform currently observed activity in epithelial tumors into durable responses
Radiation sub-study at MD Anderson Cancer Center (MDACC) to initiate 2H 2019
Sub-study of the ADP-A2M4 clinical trial with up to 10 patients to be treated
Primary endpoint is safety and secondary endpoint is RECIST v1.1 responses
Radiation is 7Gy (low dose) per lesion or isocenter to be administered before lymphodepletion
SURPASS trial (ADP-A2M4CD8) – the first next-generation approach in the clinic in multiple solid tumors to initiate later this year
IND filed April 2019
Preclinical proof-of-concept data for this next-generation SPEAR T-cell therapy were presented at AACR (Free AACR Whitepaper) 2019 (https://bit.ly/2FGlRHN)
These data indicate that addition of the CD8α homodimer to the ADP-A2M4 cells effectively enables CD4+ "helper" T-cells to adopt a CD8+ "killer" like phenotype in vitro
This is intended to speed up initial antitumor activity and broaden the antitumor response in patients
Protocol summary:
Up to 30 subjects (HLA-A*02 with MAGE-A4+)
Primary endpoint: safety and tolerability
Secondary endpoint: antitumor activity
Lymphodepletion: Flu (30 mg/m2/day) × 4 days; Cy (1800 mg/m2/day) × 2 days
Shorter stagger between patients – anticipate faster dose escalation
Starting doses of ~1 billion cells (Cohort 1) and escalation through:
Cohort 2 (1.2 to 3.0 billion cells)
Cohort 3 (3.0 to 6.0 billion cells)
Expansion phase with up to 10 billion cells
Data expected in 2020
ADP-A2M10 studies are continuing and research plans will be reassessed as more data is accumulated across the two studies
ADP-A2AFP
Data from first HCC patient treated in Cohort 2
Continuing favorable safety data as was seen in Cohort 1 presented at AACR (Free AACR Whitepaper) 2019 (https://bit.ly/2FR8Lse)
Shows transient serum AFP decrease and tumor shrinkage at first scan
Data update will be provided in 1H 2020
Off-the-shelf program (allogeneic platform)
Substantial progress with update provided in an oral presentation at the American Society of Gene & Cell Therapy Annual Meeting 2019 by Dr. Jo Brewer, VP Allogeneic Research (https://bit.ly/2UWmqma)
Conference Call and Webcast Link for Clinical and Business Update Slide Presentation today (May 6th)
The Company will host a live teleconference and slide presentation at 8:00 a.m. EDT (1:00 p.m. BST) today (Monday May 6, 2019). The live webcast of the conference call and slides will be available at View Source An archive will be available after the call at the same address. To participate in the live webinar, if preferred, please dial (833) 652-5917 (U.S. and Canada) or
+1 (430) 775-1624 (International).