ASCO review!

The 2021 American Society of Clinical Oncology (ASCO) annual meeting officially ended on June 8th, Eastern Time
.
According to the abstract of ASCO's annual meeting, many new drug researches developed by Chinese companies were selected as the oral reports of this conference this year

1.
Chia Tai Tianqing: Anlotinib

Mechanism of action: multi-target tyrosine kinase inhibitor

Abstract Number: 11505

Anlotinib is a new small-molecule multi-target tyrosine kinase inhibitor developed by Chia Tai Tianqing, which can effectively inhibit VEGFR, PDGFR, FGFR, c-Kit and other kinases

According to reports, the study aims to evaluate the efficacy and safety of anlotinib as a single agent in the treatment of patients with advanced synovial sarcoma compared with dacarbazine (a drug for the treatment of soft tissue sarcoma)
.
The data showed that the progression-free survival (PFS) of the anlotinib group was 2.
89 months, which was higher than the 1.
64 months of the control group, and reached the primary endpoint of the study; at the 4th, 6th and 12th months, receiving Anlotinib The progression-free proportions of patients treated with tinib were 48.
1%, 42.

2.
Baiji Gene: CLL1 targets CAR-T

Mechanism of action: Cell therapy products targeting CLL1

Abstract Number: 10000

CAR-T therapy has achieved remarkable success in the treatment of various blood cancers, such as CD19 targeted therapy for B-cell malignancies and BCMA targeted therapy for multiple myeloma
.
However, similar achievements have not been replicated in patients with relapsed and refractory acute myeloid leukemia (AML).

At this conference, this CAR-T therapy for the CLL1 target showed the results of a phase 1, multi-center, and mid-term clinical study initiated by the investigator in the form of an oral report
.
Data show that candidate therapies show rapid, efficient, precise and safe treatment effects in children with relapsed/refractory acute myeloid leukemia.

3.
Dizhe Pharmaceutical: DZD9008

Mechanism of action: EGFR-TKI

Abstract Number: 9008

Non-small cell lung cancer (NSCLC) accounts for 80%-85% of all lung cancers, and about 2-3% of NSCLC patients carry EGFR exon 20 insertion mutations.
These patients have poor response to common EGFR inhibitors, and the prognosis is particularly poor
.
In China, no innovative therapies for this type of patient group have been approved

At this ASCO conference, DZD9008 presented the results of a Phase 1 study in the form of an oral report
.
The data show that the candidate drug has good safety and tolerability, good oral absorption and utilization, and a long metabolic half-life in the human body

4.
Hengrui Medicine: Carrelizumab

Mechanism of action: anti-PD-1 monoclonal antibody

Abstract number: 4000, 6000

Five studies of Hengrui Medicine were selected as the oral report of the ASCO conference, involving the anti-PD-1 monoclonal antibody carrelizumab, the CDK4/6 inhibitor dapiciclib (dalpiciclib, SHR6390 tablets), PD-L1/TGF- β double anti-SHR-1701 and many other anti-tumor drugs
.
Among them, two phase 3 studies of carrelizumab for the first-line treatment of esophageal squamous cell carcinoma and nasopharyngeal carcinoma have received particular attention

One of them is a phase 3 ESCORT-1st study, which aims to evaluate the effect of carrelizumab combined with chemotherapy in untreated patients with advanced or metastatic esophageal squamous cell carcinoma
.
The data showed that after a median follow-up of 10.
8 months, carrelizumab combined with chemotherapy significantly improved the overall survival of patients (median OS, 15.
3 months vs 12.
0 months), PFS (median, 6.
9 months vs.
5.
6 months); In addition, the objective response rate (72.
1% vs 62.
1%) and the median sustained response time (7.
0 months vs 4.
6 months) of the carrelizumab group were also higher than those of the placebo group
.
The study believes that compared with placebo + chemotherapy, carrelizumab + chemotherapy can significantly improve patients' OS and PFS, with controllable safety, and may become the first-line treatment for patients with advanced or metastatic esophageal squamous cell carcinoma The new standard
.

Another phase 3 study is CAPTAIN-1st, which aims to evaluate the effect of carrelizumab combined with GP (gemcitabine + cisplatin) in the first-line treatment of recurrent/metastatic nasopharyngeal carcinoma
.
The data showed that the median PFS of the carrelizumab group was 10.
8 months and that of the placebo group was 6.
9 months; the ORR of the carrelizumab group evaluated by IRC was 88.
1%, and the ORR of the placebo group was 80.
6%; The median duration of remission (median DoR, 9.
9 months vs.
5.
7 months), DCR (96.
3% vs 94.
6%), and 18-month PFS rates (34.
8% vs 12.
7%) in the rilizumab group were also high In the placebo group
.
Based on the results of this study, the National Medical Products Administration (NMPA) of China has recently approved a new indication for carrelizumab, combined with cisplatin and gemcitabine for the first-line treatment of patients with locally recurring or metastatic nasopharyngeal carcinoma
.

5.
Sibiman Bio: C-CAR039, C-CAR066

Mechanism of action: CD20×CD19 dual-targeting CAR-T therapy, CD20 targeting CAR-T therapy

Abstract Number: 2507, 2508

At this conference, Sibman Biosciences had two researches on CAR-T therapy selected as oral reports
.
A clinical study to evaluate the safety and effectiveness of CD19×CD20 dual-target CAR-T cell therapy C-CAR039 for the treatment of relapsed or refractory B-cell non-Hodgkin’s lymphoma (B-NHL)
.
According to reports, C-CAR039 is a new type of second-generation 4-1BB dual-target CAR-T with an optimized dual-specific antigen-binding domain, which can act on both CD19 and CD20 dual targets at the same time, and can be combined in vivo.
Eliminate CD19/CD20 single-positive or double-positive tumor cells in vitro
.

The latest data show that: a median follow-up of 7 months, the best overall response rate was 92.
6%, of which a complete response (CR) rate was 85.
2%; among 24 patients with diffuse large B-cell lymphoma (DLBCL), 20 patients Obtained CR; the median time to remission was 1.
0 month, and the Kaplan Meyer assessment value of 6-month progression-free survival was 83.
2%, which did not reach the median duration of remission; 92.
9% of patients had cytokine release syndrome ( CRS), 2 patients developed grade 1 immune effector cell-related neurotoxicity syndrome
.
Studies believe that: C-CAR039 has shown good safety and promising efficacy in early clinical trials, which may make it different from existing treatment methods
.

Recurrence caused by loss of CD19 antigen is a challenge for CD19-targeted CAR-T therapy, and these patients generally have a poor prognosis
.
C-CAR066 is a new second-generation CAR-T therapy targeting CD20 antigen
.
This oral report published at the ASCO conference aims to evaluate the safety and effectiveness of C-CAR066 in patients with relapsed/refractory B-NHL who have previously received CD19-targeted CAR-T therapy
.

The data showed that the median follow-up was 4.
2 months, and the best total remission rate was 100%, of which the complete remission rate was 70.
0% (7/10); the median to remission time was 1.
0 months, and the median to complete remission time was 2.
7 The median duration of remission has not yet been reached; 4 patients developed disease progression, 2 of them lost the CD19 and CD20 antigens of their tumor cells; 1 patient suffered from CAR-T cells two months after C-CAR066 infusion Expansion and proliferation are lost and relapse; 6 patients are still in remission, 4 of which are still in CR state ten months after C-CAR066 infusion
.
The study believes that C-CAR066 has good safety and effectiveness for patients with relapsed/refractory B-NHL after failure of anti-CD19 CAR-T treatment, and it is expected to bring a new treatment plan for such patients
.

6.
Yasheng Pharmaceutical: APG-2575, APG-115

Mechanism of action: Bcl-2/Bcl-xL dual target inhibitor, small molecule MDM2 inhibitor

Abstract numbers: 7502, 2506

Bcl-2 protein is a new target for the treatment of hematological cancers, but the existing Bcl-2 inhibitors may increase the risk of adverse reactions such as tumor lysis syndrome and severe neutropenia
.
According to the press release of Ascent Pharmaceuticals, APG-2575 is China's first Bcl-2 selective inhibitor to enter the clinical stage.
It announced the latest data of a first human trial in the form of an oral report at this ASCO conference, targeting recurrence/ Patients with refractory (R/R) chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) and other hematological malignancies
.

The latest clinical data shows that APG-2575 initially shows good safety and potential anti-tumor activity for R/R CLL/SLL patients, with an objective remission rate of 80.
0%; for several other hematological malignancies, it is a candidate drug It also has potential disease control effects
.
At the same time, APG-2575 is well tolerated and adverse events are controllable
.
Yasheng Pharmaceutical believes that the product has outstanding "best-in-class" potential and will further evaluate its anti-tumor activity in other hematological tumors or solid tumors
.

At this conference, another study by Ascent Pharmaceuticals was selected as an oral report, namely: APG-115 combined with Pembrolizol in patients with unresectable/metastatic melanoma or advanced solid tumors who have failed immuno-oncology drug therapy Preliminary results of the Phase 2 clinical study of monoclonal antibodies
.
APG-115 is an oral, highly selective, small molecule MDM2 inhibitor developed by Yasheng Pharmaceutical, which restores the tumor suppressor activity of p53 by blocking the MDM2-p53 interaction
.

The latest data shows that APG-115 has preliminary clinical efficacy and good safety in a variety of refractory tumors and multiple related indications, especially for relapsed/refractory melanomas that have no standard treatment options.
Tumor
.
In the PD-1/PD-L1 inhibitor-resistant melanoma cohort, one patient achieved complete remission, with an ORR of 24.
1% and a disease control rate of 55.
2%
.
Ascent Pharmaceuticals believes that APG-115 combined with pembrolizumab is expected to break a variety of treatment dilemmas and has "first-in-class" potential
.

7.
Junshi Bio: Tereprizumab

Mechanism of action: anti-PD-1 monoclonal antibody

Abstract Number: LBA2

Teriprizumab is an anti-PD-1 monoclonal antibody developed by Junshi Biotech.
It has been approved in China for the treatment of melanoma, nasopharyngeal carcinoma, and urothelial carcinoma
.
At this conference, the Phase 3 study (JUPITER-02) of teriplimumab combined with GP (gemcitabine + cisplatin) in the first-line treatment of nasopharyngeal carcinoma was successfully selected as the oral report of this year's ASCO General Assembly
.
The Junshi Biotech press release pointed out that this research is the first Chinese local innovative drug research to be selected into the plenary meeting since the official record of the ASCO annual meeting
.

The data from the JUPITER-02 study showed that compared with chemotherapy alone, teriprizumab combined with GP chemotherapy in the first-line treatment of recurrent/metastatic nasopharyngeal carcinoma can achieve better progression-free survival (median PFS, 11.
7 months vs.
8.
0 months), higher ORR (77.
4% vs 66.
4%) and longer DoR (median, 10.
0 months vs 5.
7 months), and have good safety and tolerability
.
As of February 18, 2021, the OS in the JUPITER-02 study is not yet mature.
However, it has been observed that the combined treatment group of teriplizumab has a trend of overall survival benefit, and its risk of death has been reduced by 40%
.
Studies believe that the combination of teriprizumab and GP is expected to become a new standard for the first-line treatment of recurrent/metastatic nasopharyngeal carcinoma
.

In addition to the above studies, there are many Chinese new drug studies that have also been selected as oral reports of this conference.
Due to space limitations, this article will not introduce them one by one
.
It is hoped that these new anti-cancer drugs can come to patients as soon as possible and provide them with new treatment options
.