On November 6, 2019 CStone Pharmaceuticals ("CStone" or the "Company", HKEX: 2616) reported that an abstract on the CS1001-201 trial (Abstract #2833) was accepted by the 2019 American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and has been published online yesterday on the meeting’s official website (Press release, CStone Pharmaceauticals, NOV 6, 2019, View Source;cstones-anti-pd-l1-antibody-demonstrates-a-complete-response-rate-of-31-8-in-patients-with-relapsed-or-refractory-extranodal-natural-killert-cell-lymphoma-300953456.html [SID1234550510]). Additionally, the Company will release further updated data from the CS1001-201 trial in a poster presentation at the conference.

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CS1001-201 is a single-arm, multicenter Phase II clinical study designed to evaluate CS1001 monotherapy in relapsed or refractory extranodal natural killer (NK)/T-cell lymphoma (rr-ENKTL). The primary endpoint of the trial is objective response rate (ORR) assessed by an independent radiological review committee (IRRC); the secondary endpoints include investigator-assessed ORR, IRRC-assessed complete and partial response (CR, PR) rates, time to response, duration of response, progression-free survival, overall survival, and safety.

ENKTL is a subtype of mature T cell and NK cell lymphoma, with a higher incidence in Asia than in Europe or North America. ENKTL is an aggressive malignancy characterized by its rapid progression and poor prognosis. Patients with rr-ENKTL lack effective standard treatment after failing an L-asparaginase-based combination chemotherapy regimen. Studies to date have shown that Epstein-Barr virus (EBV) infection is linked to the pathogenic mechanisms of ENKTL, as EBV infection induces immune tolerance by upgrading PD-L1 expression in tumor cells, thus promoting tumor growth.

"In China, ENKTL accounts for approximately 6% of all lymphoma incidences, and those relapsed or refractory patients in particular have urgent unmet clinical needs. CS1001-201 is the first clinical trial worldwide investigating an anti-PD-L1 antibody in ENKTL patients, and promising initial antitumor activity has already been observed in the trial," said Dr. Frank Jiang, Chairman and CEO of CStone. "I am glad that the preliminary results from this trial will be announced for the first time at the 2019 ASH (Free ASH Whitepaper) Annual Meeting. CStone remains committed to addressing treatment gaps in China and around the world. We hope this trial will continue its rapid progress and soon produce more breakthroughs in the treatment of ENKTL."

CStone’s Chief Medical Officer, Dr. Jason Yang, noted: "The close association between ENKTL and the increased PD-L1 expression resulted by EBV infection suggests that blocking the PD-1/PD-L1 pathway could be an effective treatment for ENKTL patients. In the abstract published by ASH (Free ASH Whitepaper), CS1001 demonstrated an ORR of 40.9%, a complete and durable response rate of 31.8% and a benign safety profile. These results represent a major breakthrough in the treatment of rr-ENKTL and support the further development of CS1001 as a treatment for rr-ENKTL. We look forward to sharing encouraging additional data updates in the poster presentation at the 2019 ASH (Free ASH Whitepaper) Annual Meeting."

Results in the abstract published by ASH (Free ASH Whitepaper)

As of June 17, 2019, 29 patients were enrolled into the study. Among them, 22 (75.9%) patients had Stage IV of the disease at screening, 8 patients received 2 lines of prior treatments, and 6 patients received 3 or more lines of prior treatments. All of the patients received 1200 mg CS1001 intravenously every 3 weeks for up to 2 years, until disease progression, intolerance, etc. The median duration of follow-up was 5.55 (range, 0.69-12.19) months.

Demographics and baseline characteristics

15 (51.7%) of the 29 enrolled patients remained on treatment, and 14 (48.3%) had discontinued from the study treatment.
Reasons for discontinuations included disease progression (12 patients) and adverse events (AEs, 2 patients).
No discontinuations or deaths due to treatment-related AEs (TRAEs).
Preliminary efficacy data
CS1001 demonstrated promising antitumor activity in rr-ENKTL patients

Among the 22 efficacy-evaluable patients, the investigator-assessed ORR was 40.9%. 7 (31.8%) patients achieved complete and durable response.
2 (9.1%) patients achieved partial response (PR), and 1 additional patient achieved PR after pseudo-progression.
The duration of response (DoR) ranged from 0.03+ to 8.61+ months, and the median DoR was not reached.
The IRRC assessments were not available at the time of data cut-off.
Safety data

CS1001 was well tolerated in patients with rr-ENKTL

The median duration of treatment was 11.7 (range, 2.9 – 53.0) weeks.
25 (86.2%) patients reported treatment-emergent AEs (TEAEs).
21 (72.4%) patients reported treatment-related AEs (TRAEs), of which 3 (10.3%) had Grade ≥3 TRAEs.
Grade 5 AEs were reported in 2 patients, and none was assessed as related to CS1001.
Serious AEs were observed in 5 (17.2%) patients, and 1 of them (sinus node dysfunction) was assessed as related to CS1001 by the investigator.
Immune-related AEs (irAEs) were reported in 5 patients (17.2%). Except 1 Grade 3 rash, all irAEs were Grade 1 in severity.
TEAEs that led to permanent treatment discontinuation occurred in 2 (6.9%) patients; but no permanent discontinuation or death due to AEs were assessed as related to CS1001.
After data cut-off date, 3 additional patients reached the response assessment time point, of which 2 patients achieved CR, elevating the ORR to 44.0% (11/25) and CR rate to 36.0% (9/25). More details of the updated data will be reported at the 2019 ASH (Free ASH Whitepaper) Annual Meeting.

About CS1001

CS1001 is an investigational monoclonal antibody directed against PD-L1 being developed by CStone. Authorized by the U.S. based Ligand Corporation, CS1001 is developed by the OMT transgenic animal platform, which can generate fully human antibodies in one step. As a fully human, full-length anti-PD-L1 monoclonal antibody, CS1001 mirrors natural G-type immune globulin 4 (IgG4) human antibody, which can reduce the risk of immunogenicity and potential toxicities in patients, potentially representing a unique advantage over similar drugs.

CS1001 has completed a Phase I dose-escalation study in China, in which CS1001 showed good tolerability and produced sustained clinical benefits during Phase Ia and Ib stages of the study in multiple indications.

CS1001 is being investigated in a number of ongoing clinical trials, including one Phase I bridging study in the U.S. In China, its clinical program includes one multi-arm Phase Ib study, two pivotal Phase II studies, and three Phase III studies for several tumor types.