As of October 22, 2021, 585 eligible patients were randomized with a median follow-up duration of 12.3 months. The median OS in the serplulimab group and the placebo group were 15.4 (95% CI 13.3–NE) and 10.9 (95% CI 10.0–14.3) months, respectively, with a hazard ratio (HR) of 0.63 (95% CI 0.49–0.82; p<0.001).
The 24-month OS rate in the two treatment groups were 43.1% and 7.9%, respectively. Median progression-free survival (PFS) assessed by the independent radiology review committee (IRRC) per RECIST v1.1 was 5.7 months in the serplulimab group and 4.3 months in the placebo group (HR 0.48, 95% CI 0.38–0.59).
Efficacy improvements were also observed in objective response rate (ORR) (80.2% vs. 70.4%) and duration of response (DOR) (median, 5.6 vs. 3.2 months) as assessed by the IRRC per RECIST v1.1.
Grade 3 and above treatment related adverse events (TRAEs) related to serplulimab/placebo occurred in 33.2% in serplulimab/chemo arm versus 27.6% in chemo control arm.
Henlius has submitted the data package for for ES-SCLC to China’s NMPA and plans to submit to the EMA in the second half of 2022. Serplulimab received orphan drug designation from the FDA in April 2022.
CStone’s sugemalimab in R/R ENKTL
CStone Pharmaceutical shared phase II data of PD-L1 antibody sugemalimab in patients with relapsed or refractory extranodal natural killer cell/T-cell lymphoma (R/R ENKTL).
CStone said its sugemalimab showed OS benefit as monotherapy in patients with R/R ENKTL. The OS rates at 6 months, 12 months and 24 months were 79.2%, 68.6% and 54.6%, respectively.
In 78 evaluable patients, ORR assessed by the IRRC was 46.2% with a complete response (CR) rate of 37.2%.
As of November 10, 2021, 80 patients were enrolled in the single-arm GEMSTONE-201 study and received sugemalimab monotherapy.
Based on the evaluation by the IRRC, durable objective response was observed in patients who responded to sugemalimab. Median DOR was not reached at the time of the analysis. The 6-month and 12-month DOR rates were 90.8% and 86.0%, respectively
Sugemalimab has been granted breakthrough therapy designation by the FDA for adults with R/R ENKTL.
Junshi’s icatolimab in lymphoma and solid tumors
At the ASCO meeting, Junshi Biosciences chose to highlight its anti-BTLA monoclonal antibody, icatolimab, in addition to its PD-1 inhibitor toripalimab. It said icatolimab is the first BTLA-targeted drug against tumors in clinical trials.
In a phase I study evaluating icatolimab as a single agent or in combination with toripalimab in 31 patients with R/R lymphoma, no dose limiting toxicity (DLT) was observed in either monotherapy or combination dose escalation as of April 26 2022 (median follow-up 31.9 weeks).
Among the 25 evaluable patients receiving monotherapy, one (partial response) PR and seven stable disease (SD) were observed per Lugano criteria. Among the six patients receiving the combination, three PR (ORR 50%) and one SD were observed.
In another phase Ia trial of icatolimab in patients with advanced solid tumors, no DLTs were observed as of April 31, 2022 (median follow-up 32 weeks). Among 19 evaluable patients, one PR and seven SD were observed as assessed by the investigator per RECIST v1.1 criteria.
Icatolimab has now entered the phase Ib/II dose expansion phase. Junshi is conducting a combination trial of icatolimab and toripalimab in multiple tumor types in China and the U.S.
OriCell’s GPRC5D-directed CAR-T therapy in MM
OriCell Therapeutics drew attention this year with its Ori-CAR017, an autologous GPRC5D-directed CAR-T cell in adults with measurable multiple myeloma (MM), R/R or intolerant to established MM therapies and relapsed after BCMA-targeted therapy.
In the phase I POLARIS study, single infusion of Ori-CAR017 demonstrated an early, deep and durable responses at all dose levels in heavily pretreated R/R MM patients, including those who relapsed from BCMA CAR-T therapy.
OriCell said ORR was 100% with CR/ stringent CR (sCR) rate of 60%, including five patients with prior BCMA CART therapy achieving two sCR, two very good PR and one PR. All patients were noted as progression free without additional therapy at data cutoff.
It added that no DLTs or serious adverse events were observed. There was no immune effector cell associated neurotoxicity syndrome either, but only grade 1/2 cytokine release syndrome. Most common grade 3/4 adverse events were cytopenia mainly due to lymphodepleting chemotherapy.
OriCell said it will focus on filling an IND with the NMPA and FDA for Ori-CAR017.
Gracell’s BCMA/CD19 dual-targeting CAR-T GC012F in MM
Gracell Biotechnologies is another cell therapy specialist taking aim at MM, pinning hopes on GC012F, its autologous BCMA and CD19 dual-targeting CAR-T candidate. It is the first dual-targeting CAR-T with clinical data in R/R MM.
The company enrolled 28 heavily pretreated R/R MM patients in a single-arm, open label, multicenter investigator-initiated trial with a single infusion of GC012F at three dose levels, 1x105 cells/kg (DL1), 2x105 cells/kg (DL2), and 3x105 cells/kg (DL3).
At the data cutoff of January 26, 2022, the response rate at different dose levels was 100% (2/2) in DL1, 80% (8/10) in DL2, and 93.8% (15/16) in DL3. All 27 MRD-assessable patients achieved minimal residual disease (MRD) negativity, and 21 patients treated achieved MRD- sCR.
The safety profile of GC012F was consistent with previous findings with mostly low grade of cytokine release syndrome (CRS) (Grade 0-2 (93%)). No Grade 4 or 5 CRS, or any Grade immune effector cell-associated neurotoxicity syndrome (ICANS) were observed.
In November 2021, GC012F was granted orphan drug designation for MM by the FDA. GC012F is now in investigator-initiated trials in China for MM and B-NHL.
More Chinese players
The annual gala was also attended by plenty of other Chinese biotech firms, such as Ascentage Pharma, Alphamab, Innovent Biologics, RemeGen and BeiGene.
Ascentage presented results from a phase Ib/II study of the third-generation tyrosine kinase inhibitor olverembatinib in patients with metastatic gastrointestinal stromal tumor (GIST) who were resistant to or failed prior TKI treatment. It also updated phase II data of MDM2-p53 inhibitor alrizomadlin plus pembrolizumab in adults and children with various solid tumors.
Alphamab provided updated data of its PD-L1/CTLA-4 bispecific antibody, KN046. The candidate is in a number of studies.
The list includes a phase III study combined with nab-paclitaxel and gemcitabine versus placebo combined with nab-paclitaxel and gemcitabine in patients with advanced pancreatic cancer; a phase II study as second-line and above treatment for unresectable locally advanced or metastatic pancreatic ductal adenocarcinoma; a phase II study combined with lenvatinib in advanced unresectable or metastatic hepatocellular carcinoma; and in a phase II study in thymic carcinoma who failed immune checkpoint inhibitors.
Innovent shared data of anti-LAG-3 monoclonal antibody, IBI110. This includes the data from a phase Ia/Ib clinical study as well as preliminary results from two phase Ib proof-of-concept clinical studies in advanced squamous non-small cell lung cancer and advanced gastric cancer.
RemeGen provided data of its HER2-targeted ADC disitamab vedotin, which it licensed to Seagen in a $2.6 billion deal in 2021. The data came from three studies centered on urothelial carcinoma.
Last but not least is BeiGene. It presented data of its BTK inhibitor zanubrutinib in Waldenström macroglobulinemia and R/R follicular lymphoma. The company also shared results of its PD-1 drug tislelizumab as first-line treatment for recurrent/metastatic nasopharyngeal cancer.