On December 9, 2019 CStone Pharmaceuticals ("CStone" or the "Company", HKEX: 2616) reported that results from the CS1001-201 trial in a poster presentation at the 2019 American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting (Press release, CStone Pharmaceauticals, DEC 9, 2019, View Source [SID1234552151]).

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CS1001-201 trial 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).

ENKTL is a subtype of mature T cell and NK cell lymphoma. It has a higher incidence in Asia than in Europe or North America. ENKTL is characterized by its rapid progression and poor prognosis. Currently, patients with rr-ENKTL lack effective treatment after failing an L-asparaginase-based combination chemotherapy regimen and targeted monotherapy only produces a complete response (CR) rate of below 10%.

"ENKTL accounts for approximately 6% of all lymphoma incidences, and there are vast unmet medical needs in this patient population that has failed the first-line treatment," said Dr. Frank Jiang, Chief Executive Officer and Chairman of CStone. "The CS1001-201 trial is the first clinical study of an anti-PD-L1 antibody in ENKTL worldwide. Our latest data have shown CS1001 to be well-tolerated with preliminary antitumor efficacy and survival benefit in rr-ENKTL patients. We will continue to advance this development program and hope that CS1001 will soon become a new treatment option for rr-ENKTL patients."

"CR is a critical outcome measure for the treatment of ENKTL. Studies have shown that ENKTL patients who achieved CR prior to autologous transplantations have a significantly better prognosis and longer survival than those who achieved partial response," said Dr. Jason Yang, Chief Medical Officer of CStone. "These latest results of CS1001 demonstrated a CR rate of 33.3% with durable response, an objective response rate of 43.3%, and a 1-year overall survival rate of 72.4%. These results represent a major breakthrough compared to current treatment options and support CS1001 as a potential conditioning regimen for hematopoietic stem cell transplantations."

Overview of the CS1001-201 trial

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 ORR assessed by an independent radiological review committee (IRRC);
Secondary endpoints include investigator-assessed ORR; IRRC-assessed CR and PR rates, time to response, duration of response, progression-free survival; overall survival, and safety.
Results reported in the poster at the 2019 ASH (Free ASH Whitepaper) Annual Meeting

As of October 8, 2019, 32 patients were enrolled in the study. Among them, 24 patients (75.0%) had Stage IV ENKTL at screening, 9 patients (28.1%) received 2 lines of prior treatments, and 7 patients (21.9%) received 3 or more lines of prior treatments. All 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 6.54 months (range, 0.72-15.64).

13 (40.6%) of the 32 enrolled patients remained on treatment, and 19 (59.4%) had discontinued from the study treatment.
Reasons for discontinuations included radiographic disease progression (12 patients), adverse events (AEs, 4 patients), and non-radiographic symptomatic progression (3 patients).
No deaths due to treatment-related AEs (TRAEs).
Preliminary efficacy data

CS1001 demonstrated promising antitumor activity and a favorable CR rate with durable response and survival benefit in rr-ENKTL patients.

Among the 30 efficacy-evaluable patients, the investigator-assessed ORR was 43.3%.
10 patients (33.3%) achieved CR and were still in remission.
3 patients (10.0%) achieved partial response (PR), and 1 additional patient achieved PR after pseudo-progression. The median duration of response (DoR) was not reached, and the maximum DoR was 10.9+ months.
The 1-year overall survival (OS) was 72.4% (95% CI: 52.0%-85.2%).
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 12.6 weeks (range, 3.0-69.1).
30 patients (93.8%) reported treatment-emergent AEs (TEAEs).
24 patients (75.0%) reported TRAEs, of which 3 (9.4%) had Grade >3 TRAEs.
Grade 5 AEs were reported in 3 patients (9.4%), and none was assessed as related to CS1001.
7 patients (21.9%) reported serious AEs (SAEs). 1 case of Grade 4 sinus node dysfunction and 1 case of Grade 1 myositis were assessed as related to CS1001 by the investigator. Both patients later recovered from the SAEs.
Immune-related AEs (irAEs) were reported in 5 patients (15.6%). Except for 1 Grade 3 rash, all irAEs were Grade 1 in severity.
TEAEs that led to permanent treatment discontinuation occurred in 4 patients (12.5%).
No deaths due to AEs were assessed as related to CS1001.
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 is similar to natural G-type immune globulin 4 (IgG4) human antibody, which can reduce the risk of immunogenicity and potential toxicities, 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 the Phase Ia study.

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.