Suzhou's CStone Pharma (HK: 2616) released positive results from a China Phase II trial of its PD-L1 candidate (CS1001) as a monotherapy in relapsed or refractory extranodal natural killer (NK)/T-cell lymphoma (rr-ENKTL). CS1001, developed using Ligand's OMT OmniAb® transgenic rodent platform which can generate fully human antibodies in one step, produced an overall response rate of 41%, a complete and durable response rate of 32% and a benign safety profile. The company says studies have shown links between Epstein-Barr virus (EBV) infection and ENKTL. EBV infection induces immune tolerance by upgrading PD-L1 expression in tumor cells, promoting tumor growth. CStone is developing a pipeline of 15 oncology drug candidates. In February, it completed a $285 million Hong Kong IPO.

CS1001 is currently being tested in several clinical trials, including one Phase I bridging study in the US. In China, its clinical program includes one multi-arm Phase Ib study, two pivotal Phase II studies, and three Phase III studies for various tumor types.
CStone will present results from the trial at the 2019 American Society of Hematology (ASH), including updated data from the CS1001-201 trial in a poster presentation at the conference.

CS1001-201 is a single-arm, multicenter Phase I clinical trial. Its primary endpoint is objective response rate (ORR) assessed by an independent committee; the secondary endpoints include investigator-assessed ORR, 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.

"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.

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.

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.

Results

• 15 (51.7%) of the 29 enrolled patients remained on treatment, and 14 (48.3%) discontinued 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).

Efficacy:

• 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.

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Disclosure: none.