On September 13, 2021 Adaptimmune Therapeutics plc (Nasdaq: ADAP), a leader in cell therapy to treat cancer, reported updated data from its Phase 1 SURPASS trial in multiple solid tumors to be presented in a digital poster at the upcoming European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) annual meeting (Press release, Adaptimmune, SEP 13, 2021, View Source [SID1234587584]). The poster will be displayed on the ESMO (Free ESMO Whitepaper) congress web site on Thursday, September 16th. The Company has also released a video of Adrian Rawcliffe, Adaptimmune’s Chief Executive Officer (CEO), and Elliot Norry, Adaptimmune’s Chief Medical Officer, describing these data in more detail that can be accessed here: https://bit.ly/38ZQCGt.
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"It is no longer a question of whether our SPEAR T-cells are effective against a range of MAGE-A4 expressing tumors — they undoubtedly are. Now, our focus is on turning them into approved therapies. This begins with ongoing recruitment in this SURPASS trial for people with lung, bladder, gastroesophageal, head and neck, and now ovarian cancer, and continues with the recently initiated SURPASS 2 trial in esophageal and EGJ cancers," said Adrian Rawcliffe, Adaptimmune’s CEO. "These data bring us closer to identifying further indications to take into late-stage development and confirm our expertise in developing and enhancing cell therapies. ADP-A2M4CD8 does exactly what we designed it to do — kill cancer cells and more effectively engage the broader immune system to deliver improved potency and clinical benefit."
Dr. David Hong, Professor, Deputy Chairman in the Department of Investigational Cancer Therapeutics (Phase I Program) at The University of Texas MD Anderson Cancer Center said, "We are encouraged by these promising early data from the SURPASS trial. Having previously seen strong responses with afami-cel, this next-generation cell therapy appears safe and demonstrated antitumor activity for a majority of patients across many cancer indications."
Topline results from the Phase 1 SURPASS trial (data cut-off August 2, 2021)
Emerging efficacy and durability data are promising with responses in five solid tumor indications
As of the data cut-off date, 25 patients had received the next-generation cell therapy, ADP-A2M4CD8, in the Phase 1 SURPASS trial, 22 patients were evaluable for efficacy with at least one post-baseline scan meeting the ≥4-week duration for evaluation of stable disease
All patients had advanced metastatic disease and had received multiple prior regimens of systemic therapy (median: 3; range 1-6)
The overall response rate was 36% and the disease control rate was 86%
There was a complete response reported in a patient with ovarian cancer, which remains ongoing at 6 months post‑infusion (data on file at Adaptimmune)
Initial durability is encouraging. As of the data cut-off, 11 patients remain on study. Of the 8 responders, 5 remain in response with some remaining progression free >24 weeks
Best Overall Response (n=22)* Overall, n (%) Cancer Indication
(n=1 unless otherwise noted)
Complete response (CR) 1 (4.5) Ovarian
Partial response (PR) 7 (31.8) Ovarian (2); head and neck (2)**; esophagogastric junction (EGJ)**; bladder; synovial sarcoma
Stable disease (SD) 11 (50.0) Ovarian cancer (3); EGJ (2); esophageal (2); lung cancer, MRCLS, melanoma,
Progressive disease (PD) 3 (13.6) EGJ, lung, ovarian
Overall response rate (CR, PR) 8 (36.4)
Disease control rate (CR, PR, SD) 19 (86.4)
* Of 25 patients who received ADP-A2M4CD8, 3 were not evaluable at the time of data cut-off: 2 patients (ovarian or esophageal cancers) did not have post-baseline scans; 1 patient (EGJ) had a post-baseline scan that did not meet the ≥4-week duration for evaluation of stable disease
** One PR in head and neck cancer and one PR in EGJ cancer were reported previously at SITC (Free SITC Whitepaper) 2020
ADP-A2M4CD8 demonstrated an acceptable safety profile
Eighteen (72%) patients experienced cytokine release syndrome (CRS) related to T-cell infusion, most of which were lower grade: Grade 1 or 2 (n=14); Grade 3 (n=4)
The most common serious adverse event (SAE) of any grade (> 30% of patients) was CRS
Four (16%) patients experienced immune effector cell-associated neurotoxicity syndrome (ICANS) related to T-cell infusion: Grade 1 (n=1); Grade 2 (n=1); Grade 3 (n=2)
Five (20%) patients experienced prolonged cytopenia at Week 4
One patient experienced a fatal (Grade 5) SAE of pancytopenia (previously reported in the Company’s 10K Report filed with the Securities and Exchange Commission on February 25, 2021)
ADP-A2M4CD8 was designed to be more potent than the first-generation product
Adaptimmune’s Specific Peptide Enhanced Affinity Receptor (SPEAR) T-cell therapies are a mix of CD8+ ("killer") and CD4+ ("helper") T-cells engineered with a T-cell receptor (TCR) designed with Adaptimmune’s proprietary affinity enhancement technology to recognize a cancer target
ADP-A2M4CD8 is a next-generation T-cell therapy engineered to target MAGE-A4 positive tumors, and to express a CD8α co-receptor
ADP-A2M4CD8 uses the same engineered T-cell receptor that recognizes MAGE-A4 as Adaptimmune’s first-generation T-cell therapy, afami-cel, which has shown compelling results in synovial sarcoma and myxoid/round cell liposarcoma (presented at ASCO (Free ASCO Whitepaper) 2021)
Co-expression of CD8α adds CD8+ killer cell capability to CD4+ helper T-cells, while maintaining or enhancing the CD4+ helper function (i.e., producing the inflammatory cytokines IFN-γ and IL-2)
Initial translational data confirm that ADP-A2M4D8 is more potent and better engages the immune system, compared to the first-generation product
Patient manufactured product and serum samples from the first-generation Phase 1 afami-cel trial and the next-generation SURPASS trial were compared
In vitro tumor cell killing assays confirm that the next-generation product results in greater tumor cell killing by CD4+ SPEAR T-cells
Analyses of patient serum samples demonstrate increases in a subset of 22 measured serum cytokines confirming increased helper function of the next-generation CD4+ T-cells and engagement of the broader immune system
Additional serum analyses showed increased serum IL-12 in the SURPASS trial versus the first-generation Phase 1 trial, which is also consistent with engagement of the broader immune system, including dendritic cells, as IL-12 is not known to be produced by T-cells
Conclusions from the Phase 1 SURPASS Trial Data at ESMO (Free ESMO Whitepaper)
Initial efficacy and durability data are encouraging with responses across five different solid tumors including a complete response in a patient with ovarian cancer ongoing at 6 months
The safety profile of the next-generation ADP-A2M4CD8 cell therapy was acceptable
Data confirm preclinical observations that the enhanced TCR interaction in ADP-A2M4CD8 results in a more potent product
Safety and efficacy, including duration of response, will continue to be evaluated in the ongoing SURPASS trial, which is enrolling eligible patients with gastroesophageal, head and neck, lung, bladder, and ovarian cancers
A Phase 2 trial, SURPASS-2, has initiated for patients with esophageal and EGJ cancers
Overview of Phase 1 SURPASS trial design
This is a Phase 1, open-label, dose escalation clinical trial designed to evaluate the safety and antitumor activity of ADP-A2M4CD8 in patients with MAGE-A4+ tumors in the context of HLA-A*02
This is a first-in-human dose-escalation trial using a modified 3+3 design, with 2 dose cohorts plus an expansion cohort
The number of transduced cells ranged from 0.8×109 to 1.2×109 (Cohort 1 complete), 1.2×109 to 6.0×109 (Cohort 2 complete), and 1.2×109 to 10.0×109 (Expansion)
Dose-limiting toxicities are adjudicated by a Safety Review Committee, regardless of the investigator’s attribution
Responses are assessed per RECIST v1.1