The 2022 CSCO | was full of wonderful and colorful flowers, and the special session on innovative drug clinical research data was held in Beijing

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The 25th National Congress of Clinical Oncology and the 2022 CSCO Annual Conference were held
in Beijing on November 5.
The conference focuses on the clinical frontier of oncology, invites well-known experts and scholars at home and abroad to make wonderful progress reports or lectures, and strives to comprehensively and accurately reflect new concepts and new trends
in the field of clinical oncology.
In the special session on clinical research data of innovative drugs, 12 professors brought 13 latest researches to share the research results and progress
of new drugs in various fields focusing on lung cancer, breast cancer, urothelial cancer, melanoma, ovarian cancer and other fields.

I.
Innovative Drug Clinical Research Data Session 1 Session 1 - Focus on the Frontier Progress of Lung Cancer and Sing the "Voice of China"

This part is co-chaired by Professor Yu Jinming, academician of the Chinese Academy of Engineering and president of Shandong Provincial Cancer Hospital, Professor Cheng Ying of Jilin Provincial Cancer Hospital, Professor Wang Jie and Professor Shi Yuankai of the Cancer Hospital of the Chinese Academy of Medical Sciences.

1.
Professor Cheng Ying: Phase I study of dose escalation and dose amplification of Lurbinectedin in the treatment of advanced solid tumors

This is a single-arm, open-label, multicenter, multiple-dose, dose-escalation and dose-expanded Phase I clinical trial conducted in China to evaluate the safety, tolerability, pharmacokinetic (PK) profile and preliminary efficacy
of Lurbinectedin in Chinese patients with advanced solid tumors, including recurrent small cell lung cancer (SCLC).
The study consisted of two phases, the first dose-escalation phase aimed to determine the dose-limiting toxicity and recommended dose
of Lurbinectedin monotherapy in patients with advanced solid tumors in China.
The subsequent expansion phase is to apply the established recommended dose to patients with recurrent SCLC after failure of first-line platinum-based chemotherapy to evaluate indicators such as
the efficacy and safety of Lurbinectedin in this population 。 The results suggest that the efficacy of Lurbinectedin in Chinese patients with recurrent SCLC who have failed first-line platinum-containing chemotherapy is comparable with the efficacy results of the SCLC cohort of the foreign phase II basket trial, with a better overall response rate (ORR: 45.
5% vs 30.
5%), and tends to have a better survival benefit (mPFS: 5.
6 months vs 3.
5 months, mOS: 11.
0 months vs 9.
3 months; IRC assessment, data immature).

The safety and tolerability of Lurbinectedin in Chinese groups were generally acceptable, and the PK characteristics of Chinese groups were similar
to those in European and American populations.

2.
Professor Duan Jianchun: Phase Ib clinical study of YK-029A in the treatment of treatment-naïve patients with EGFR ex20ins mutation in late NSCLC

This study is a multicenter, open-label, phase I registration clinical trial (clinical trial approval: 2018L02052), with a total of 15 cases enrolled in cohort 1 (treatment, 150mg, QD), 10 cases in cohort 2 (treatment, 200mg, QD) and 28 cases in cohort 3 (treatment-naïve, 200mg, QD), with the primary endpoint ORR and secondary endpoints including PFS, DOR, DCR and safety
。 The results showed that in this preliminary analysis of the early study, YK-029A tablets significantly improved the ORR (68.
4%) of NSCLC patients with treatment-naïve EGFR ex20ins mutation, with a DCR of 94.
7% and a 6-month DOR rate of 64.
6%.

At the cut-off time of data, median DOR and median PFS were not achieved at a median follow-up of 7.
3 months, indicating a lasting benefit and a manageable
safety profile.
Most participants had a good benefit after receiving YK-029A tablets and were not limited
by the presence or absence of brain metastases, type of EGFR ex20ins mutation, and location of insertion of EGFR ex20in mutations.
In addition, based on the data results of the phase Ib 20ins-naïve cohort, YK-029A tablets have been certified
as breakthrough therapies by NMPA.

3.
Professor Yuan Shuanghu: Stratified risk and prognosis of pIIIA-N2 non-small cell lung cancer with radical resection

In this review, patients with pIIIA-N2 non-small cell lung cancer who had radical resection were retrospectively included, and all patients underwent adjuvant chemotherapy or chemoradiotherapy according to the clinical situation, and the main indicators were the positive rate of NGS at postoperative margins, disease-free survival (DFS) and overall survival (OS).

This study explored whether the detection of minimal residual lesions (MRD) in surgical margin tissue can be used as a stratified marker for recurrence risk and prognosis of pIIIA-N2 non-small cell lung cancer with radical resection
.
The results suggest that the NGS test results can be used as a supplement to the pathological R0 detection, and the DFS and OS of postoperative patients with positive molecular margins are significantly lower than those in negative patients (p<0.
05), and postoperative molecular margin status is an independent predictor of recurrence risk in postoperative patients, and patients with positive molecular margins may suggest a new treatment strategy to replace adjuvant therapy
.

4.
Professor Mengzhao Wang: Preliminary results of a phase II pivotal study of suvortinib (DZD9008) in patients with non-small cell lung cancer with EGFR exon 20 insertion mutation

WU-KONG6 is a phase II, single-arm, multicenter clinical study
.
The results suggest that suvortinib (DZD9008) shows good antitumor efficacy at selected phase II dose levels in adult NSCLC patients with EGFR exon 20 insertion mutations who have failed or cannot tolerate previous platinum-containing chemotherapy, and both IRC and investigator-evaluated cORR are above 40%, showing significant and robust efficacy
of suvortinib.
The cORR assessed by IRC was 59.
8% (58/97 patients, 95% CI: 49.
3%, 69.
6%) and was effective
.
The maximum DoR > 8 months as of the cut-off date, and more than 70% of remission cases are still in treatment and remission
.
Efficacy was seen in participants with brain metastases at baseline, with an IRC-assessed cORR of 48.
4%.

Suvortinib is effective against all ERGFR exon 20 insertion mutation subtypes, with an ORR of 57.
1% to 63.
2%.

In addition, the effectiveness of suvortinib was largely independent of gender, age, smoking status, number of front-line treatment lines, and immunotherapy status, and the cORR assessed in each subgroup IRC was more than
45%.
Rapid onset of action after treatment with suvortinib, approximately 90% of remission occurred at the first tumor assessment, and the median onset of response time was 42.
0 days
.

5.
Professor Yu Yan: AdvanTIG-105: Phase Ib dose expansion study of oselsalimab + tislelizumab combined with chemotherapy in the treatment of metastatic squamous and non-squamous non-small cell lung cancer

The AdvanTIG-105 study (NCT04047862) is an open-label, multicenter, Phase Ib clinical trial that reported data
from Phase Ib dose expansion cohorts 1 and 2.
The results suggest that the ORRs of cohorts 1 and 2 were 57.
5% and 54.
8%, respectively, and that 23 patients in each cohort achieved partial remission, and the median DoR had not yet been reached
.
Oselsalimab and tislelizumab in combination with chemotherapy have shown antitumor activity in patients with metastatic squamous and non-squamous non-small cell lung cancer, and the safety profile of oselsalimab in Phase II recommended doses (RP2D) in combination with tislelizumab and chemotherapy is controllable
.

6.
Professor Yuming Zhu: A prospective, randomized controlled clinical study of recombinant human adenovirus type 5 injection combined with neoadjuvant chemotherapy for preoperative stage III lung cancer

This study is a prospective, randomized, open-label, controlled, single-center clinical trial of H101 combined with neoadjuvant chemotherapy in stage III lung cancer, aiming to evaluate the efficacy and safety of recombinant human adenovirus type 5 combined with neoadjuvant chemotherapy in patients with preoperative stage III lung cancer, and further analyze its efficacy in patients with p53 gene mutation, in order to provide a reference
for the formulation of more precise and individualized treatment plans for stage I lung cancer.
The study was divided into a screening period, a baseline period, a treatment period, and a follow-up period
.
The experimental group was given recombinant human adenovirus type 5 injection + neoadjuvant chemotherapy, the control group was given simple neoadjuvant chemotherapy, H101 was selected according to the size of the lesion, and the neoadjuvant chemotherapy regimen was selected
according to the tumor condition of the subjects.
The primary endpoint of this study was pathologically significant response rate, which is currently one of
the commonly used indicators reflecting neoadjuvant chemotherapy.
Recruitment began on January 20, 2022 and is expected to end
on December 30, 2022.

7.
Professor Shi Yuankai: Phase II clinical study of Iruac (WX-0593) in the treatment of crizotinib-resistant/unused ROS1-positive non-small cell lung cancer patients with crizotinib

This is an open-label, non-randomized, single-arm, multicenter, phase II clinical trial with primary endpoints of IRC-assessed ORR, and secondary endpoints including investigator-assessed ORR, DoR, DCR, PRF, TTP, intracranial objective response rate, OS, and adverse events
.
The results suggest that Iruac has shown good efficacy in ROS1-positive NSCLC patients who have not previously used crizotinib, with an overall ORR of 74% and a DCR of 96%.

Among the 13 patients with baseline brain metastases, the ORR was 61.
5% and the DCR was 100%.

Three patients had intracranial measurable lesions at baseline, one intracranial tumor reached PR, and two had SD.

In addition, Iruac showed efficacy signals in crizotinib-resistant ROS1-positive NSCLC patients, with an ORR of 22.
2% (2 PRs), a DCR of 66.
7%, and a 6-month response rate of 100% in 9 crizotinib-resistant patients, and as of data analysis, patients continued to take the drug
.
Moreover, Iruac has a good safety profile in patients with ROS1-positive NSCLC, and the safety profile is consistent
with previous reports.

8.
Professor Lu Shun: AdvanTIG-105: Phase Ib dose expansion study of osperlimab combined with tislelizumab in the treatment of metastatic non-small cell lung cancer

The AdvanTIG-105 study (NCT04047862) is an open-label, multicenter, Phase Ib clinical trial that reported data
from Phase Ib dose expansion cohort 3.
The results suggest that oselsalimab in combination with tislelizumab shows antitumor activity
in first-line PD-L1-positive (TC≥1%) patients with metastatic non-small cell lung cancer.
Combination therapy had antitumor activity in PD-L1 TC 1-49% and PD-L1 TC≥50% of patients, with PD-L1 TC≥50% having a higher
response rate.
The safety profile of oselsalimab in combination with tislelizumab was manageable, and most treatment-related adverse events were grade 1 or 2 in severity
.

2.
Innovative drug clinical research data session 1 session 2 - multi-tumor and multi-strategy, enjoy academic feast

The session was co-chaired by Professor Jiang Zefei, Vice President and Secretary-General
of the Chinese Society of Clinical Oncology (CSCO), and Professor Guo Jun of Peking University Cancer Hospital.

1.
Professor Yu Zhigang: Multicenter clinical study (cTRIO) of tislelizumab combined with carboplatin and albumin paclitaxel in neoadjuvant therapy in triple-negative breast cancer (TNBC): preliminary analysis data

cTRIO study is a national multicenter, open-label, phase II clinical study of immunoneoadjuvant therapy + adjuvant therapy in patients with early-stage TNBC, and is the first national multicenter TNBC immunoneoadjuvant therapy study
based on Chinese population.
The results suggest that tislelizumab combined with TP chemotherapy brought significant pCR benefit, with pCR (ypT0/Tis ypN0) reaching 62.
0% and pCR (ypT0ypN0) reaching 48.
0%.

The incidence of ≥ and 3rd grade TRAE in tislelizumab plus TP chemotherapy was 54.
0%, and no new safety signals
were identified.

2.
Professor Zhang Jian: DZD1516, a highly selective HER2 tyrosine kinase inhibitor that can completely penetrate the blood-brain barrier, preliminary data of non-clinical studies and phase I clinical studies

DZD1516 is an oral, highly effective, reversible and selective HER2 TKI
that fully penetrates the blood-brain barrier.
In animal models, DZD1516 was able to inhibit tumor growth in both HER2-expressing BT474c1 mouse brain metastases and subcutaneous models, and the efficacy was dose-related.
In the HER2-high expression BT474c1 mouse brain metastasis model, DZD1516 combined with T-DXd had a synergistic anti-tumor effect
.
In clinical trials that included patients with HER2-positive advanced breast cancer with or without central nervous system metastases who had failed or were intolerant to standard therapy, the aim was to assess the safety and tolerability of DZD1516 and determine the maximum tolerable dose (if possible).

The results suggest that DZD1516 has good safety and tolerability, and no adverse events (such as diarrhea, rash, etc.
) associated with wild-type EGFR suppression have been reported at MTD and below doses
.
DZD1516 has good pharmacokinetic properties and excellent blood-brain barrier permeability, and the combined systemic exposure of DZD1516 and DZ2678 increases
with dose increase in the dose range of 50mg-250mg.
In patients with brain metastases, the K_{puu and CSF} (arithmetic mean) of DZD1516 and DZ2678 were 2.
1 and 0.
76
, respectively.
DZD1516 may provide a new treatment option for patients with HER2-positive breast cancer, and follow-up clinical studies are planned
.

3.
Professor Guo Jun: A randomized controlled phase III clinical study of vedicitumab (RC48) combined with teripulimab in the first-line treatment of patients with locally advanced or metastatic urothelial cancer

The RC48-C014 study is a investigator-initiated Phase Ib/II study (ITT) to evaluate the safety and efficacy
of vedicitumab (RC48) in combination with teripulimab in locally advanced or metastatic urothelial cancer.
The efficacy data of 39 cases showed that the confirmed objective response rate reached 71.
8% (95% CI: 55.
1, 85), of which the objective response rate of first-line treatment was 73.
9%, and the disease control rate reached 92.
3%.

As of October 2022, 41 patients were enrolled overall, with a median PFS of 9.
5 months
.
The RC48-C016 study is a randomized, controlled, open-label, multicenter III clinical trial designed to evaluate the efficacy and safety
of vedicitumab (RC48) plus teripulimab versus gemcitabine plus cisplatin/carboplatin in first-line treatment of patients with urothelial carcinoma.
As of October 2022, 59 clinical research centers have been launched nationwide, and 45 patients
have been enrolled so far.
Overall, the safety is controllable and the efficacy is considerable
.

4.
Professor Guo Jun: Recombinant human GM-CSF oncolytic herpes simplex virus type II (OH2) injection monotherapy or in combination with HX008 in the treatment of patients with inoperable advanced melanoma: an open-label phase I study

Oncolytic viruses are a class of viruses
that are natural or genetically edited to specifically replicate in tumor cells and exert anti-tumor effects.
OH2 was genetically modified to delete the neurotoxic factor ICP34.
5 to promote selective replication of the virus in tumor cells and enhance safety; the virulence gene ICP47 was deleted, which reduced immunosuppression, promoted viral replication and enhanced anti-tumor efficacy; GM-CSF was inserted to induce a stronger, durable and specific anti-tumor immune response
.
The results of the clinical study of OH2 injection alone or in combination with HX008 in the treatment of unresectable advanced melanoma showed that in terms of safety, the common adverse reaction was fever and no DLT; The severity of adverse reactions in the single-agent group was grade 1/2, and the acute pancreatitis in the combined group was grade 3 (cured); During the clinical trial, no biosafety problems
such as virus shedding occurred.
In terms of efficacy, a trend towards survival benefit was observed, particularly in the subgroup of populations who failed PD-1 treatment and had disease stage III-IVM1a
.
In the OH2 injection monotherapy group, the median follow-up time was 19.
6 months, mOS was not achieved, ORR was 21.
6%, and DCR was 56.
8%.

The ORR of 8 participants who had previously failed PD-1 treatment and had disease stage III-IVM1a was 62.
5%.

5.
Professor Li Ning: PRIME study: Efficacy and safety of maintenance therapy with niraparib individualized starting dose for newly diagnosed advanced ovarian cancer, a randomized, double-blind, placebo-controlled, phase III trial

The PRIME study is a randomized, double-blind, placebo-controlled, phase III trial (NCT03709316) designed to prospectively evaluate the efficacy and safety of an individualized starting dose of niraparib as maintenance therapy for first-line platinum-based chemotherapy remission in patients with newly diagnosed advanced ovarian cancer, regardless of
biomarkers and postoperative residual disease status 。 The PRIME study prospectively demonstrated a statistically significant and clinically significant
benefit of niraparib as first-line maintenance therapy for newly diagnosed advanced ovarian cancer, regardless of biomarker status and postoperative residual disease status.
Although OS data were not yet mature, a trend of
benefit in the niraparib group was observed at data cut-off.
All patients were prospectively given an individualized starting dose, and the safety profile of niraparib improved
.
The PRIME data again confirm that niraparib monotherapy maintenance is the standard of care after first-line platinum-containing chemotherapy, regardless of
biomarker status.