ASCO GI Kangfang Bio, Junshi Bio, and Innovent Announce the Latest Clinical Data

Article source: Pharmaceutical Guanlan

The 2022 American Society of Clinical Oncology Symposium on Gastrointestinal Oncology (ASCO-GI 2022) will be held January 20-22, 2022 in a live + virtual session
.
This year's ASCO GI discussed the most innovative scientific progress in the field of digestive system tumors.

Kangfang Bio: first-line treatment of advanced gastric cancer or gastroesophageal junction adenocarcinoma with caldoniri

Cardonili (R&D code: AK104) is a PD-1/CTLA-4 bispecific antibody developed by Asofang Bio
.
At this ASCO-GI conference, Professor Ji Jiafu, Dean of Peking University Cancer Hospital, orally reported the data of Phase 1b/2 clinical study of Cardonil combined with chemotherapy in the treatment of advanced gastric cancer or gastroesophageal junction adenocarcinoma (G/GEJ).

According to the press release, in this clinical study, patients were enrolled in the first-line untreated advanced gastric cancer regardless of PD-L1 expression levels
.
During the dose-escalation and dose-expansion phases of 1b, patients received AK104 (4 mg/kg, 6 mg/kg, 10 mg/kg Q2W or 15 mg/kg Q3W) and XELOX (oxaliplatin + capecitabine, respectively) ); in the dose-confirmation phase of Phase 2, patients received AK104 (6 mg/kg Q2W or 10 mg/kg Q3W) in combination with XELOX

The latest research results show that a total of 98 patients were enrolled in the study, and the proportion of the population with PD-L1 CPS ≥ 5 was only 15%
.
As of 2021/12/31, 91 patients had at least one post-baseline tumor assessment: the objective response rate (ORR) reached 68.

At the same time, AK104 still maintains significant efficacy and safety in patients with low PD-L1 expression: in patients with PD-L1 CPS ≥ 1 and CPS < 1, the median OS was 17.
41 months and 14.
65 months, respectively; In the mature data of the /kg and 6mg/kg dose groups, there is also a significant advantage for the population with PD-L1 CPS<5, the mOS reaches 17.
2 months, and the contribution to the whole population is better than that of PD-1 therapy
.
In addition, compared with PD-1 monoclonal antibody, AK104 found no new safety signal and has good safety

According to the press release of Kangfang Bio, this clinical study is the world's first clinical study of PD-1/CTLA-4 bispecific antibody combined with chemotherapy for the first-line treatment of metastatic gastric cancer.
exploration is of great significance
.
Currently, a Phase 3 pivotal registration trial of AK104 combined with chemotherapy in the first-line treatment of advanced gastric or gastroesophageal junction adenocarcinoma is underway, and multiple studies of the combination therapy in solid tumors have been conducted worldwide

Junshi Bio: Two studies of toripalimab in first-line treatment of hepatocellular carcinoma

At the conference, Junshi Bio announced two research results of the PD-1 inhibitor toripalimab in the first-line treatment of hepatocellular carcinoma (HCC)
.
One of them is a single-arm phase 2 study of toripalimab combined with bevacizumab in first-line treatment of advanced hepatocellular carcinoma.

The results showed that the objective response rate (ORR) and disease control rate (DCR) assessed by the investigator according to the RECIST 1.
1 criteria were 32.
7% and 78.
8%, respectively, and the ORR and DCR assessed by the independent review committee according to the mRECIST criteria were 46.
2% and 94.
2%, respectively.
%
.
In terms of clinical benefit, the median progression-free survival (PFS) was 9.

The other is a phase 2 study ALTER-H003 of anlotinib combined with toripalimab in first-line treatment of patients with unresectable hepatocellular carcinoma
.
The primary endpoint of the study was ORR, and secondary endpoints were PFS, OS, DCR, duration of response (DoR), and safety
.
As of September 18, 2021, the study has enrolled 31 patients with previously unresectable hepatocellular carcinoma (uHCC)
.

The latest results showed that among 26 patients with evaluable efficacy, the confirmed ORR and DCR were 34.
6% and 92.
3%, respectively (mRECIST criteria)
.
The preliminary median PFS was 10.
2 months, and the median OS was immature
.
DoRs ranged from 1.
38-9.
69 months
.
In terms of safety, the incidence of TRAEs was 90.
3% (28/31), the incidence of grade 3 and above TRAEs was 45.
2% (14/31), and no grade 4 TRAEs were observed
.
The researchers believe that the antitumor efficacy of toripalimab combined with anlotinib in the first-line treatment of unresectable hepatocellular carcinoma is promising and the toxicity is controllable
.

Innovent Biologics/Lilly: A study of sintilimab combined with bevacizumab in the treatment of advanced hepatocellular carcinoma

At ASCO GI 2022, Innovent and Eli Lilly and Company presented final clinical study results and biologics of sintilimab combined with bevacizumab in advanced hepatocellular carcinoma in phase 1b in abstract form Marker analysis
.

According to the press release, this is a phase 1b trial to evaluate the safety, tolerability and antitumor activity of the combination therapy in Chinese patients with locally advanced/metastatic hepatocellular carcinoma who have not been treated with systemic therapy or have failed systemic therapy
.
The study is divided into two parts, the first part is a dose escalation study and the second part is a dose expansion study
.
A total of 50 subjects were enrolled in the study, including 29 subjects in the low-dose group and 21 subjects in the high-dose group, respectively
.

The results of this test study are as follows:

In terms of efficacy, the overall objective response rate (ORR) was 34% (17/50), with ORRs of 31% and 38% in the low-dose and high-dose groups, respectively
.
The overall disease control rate (DCR) was 78% (39/50)
.
The median progression-free survival (PFS) was 10.
5 months, and the median overall survival (OS) was 20.
2 months
.

Further biomarker analysis showed that subjects with CD137 serum concentrations ≥31.
8 pg/mL had longer PFS (mPFS: 14.
2 vs.
4.
1 months) and OS (mOS: not reached vs.
15.
6 months)
.
Analysis of the tumor immune microenvironment showed that a high density of interstitial M1 macrophages (CD68+, CD163-) was significantly associated with better efficacy, longer PFS and OS
.

In terms of safety, the safety characteristics of the combined treatment regimen were consistent with the results of previously reported clinical studies, and there were no new safety signals
.
The most common treatment-related adverse events (TRAEs) included hypertension, proteinuria, and pyrexia
.
The incidence of grade ≥3 adverse events in the low-dose and high-dose groups was 13.
8% and 28.
6%, respectively
.

Note: The original text has been deleted

References:

[1] ASCO-GI22 | The study of toripalimab combined with anti-angiogenic drugs in the first-line treatment of liver cancer refills new evidence.
Retrieved Jan 19, 2022, from https://mp.
weixin.
qq.
com/s/j1IexqAqfvZ4r13NPz3hqg

[2] Innovent and Eli Lilly will jointly announce the final clinical results and biologics of the Phase Ib study of Dabosu (sintilimab injection) combined with bevacizumab in the treatment of advanced hepatocellular carcinoma at ASCO GI in 2022 Marker Analysis Results.
Retrieved Jan 22, 2022, from https:// The Phase Ib/II clinical study results of Cardonilide (PD-1/CTLA-4 dual antibody) in the first-line treatment of advanced G/GEJ adenocarcinoma will be released in 2022 ASCO GI.
Retrieved Jan 24, 2022, from https:// mp.
weixin.
qq.
com/s/9yYmbMN3J5Zcd6k_K-vi2w