2022 CSCO Professor Li Ning: The urgent need for new drugs drives new options for the treatment of platinum-resistant recurrent ovarian cancer

preface

The 25th National Congress of Clinical Oncology and the 2022 CSCO Annual Conference were held
from November 5th to 12th.
The theme of this conference is "Precision Innovation, Intelligent Humanities", the conference focuses on the clinical frontier of oncology, joins hands with experts and scholars in the field of oncology across the country, shares clinical research and innovation results, and strives to comprehensively and accurately reflect new concepts and new trends
in the field of clinical oncology.
During the meeting, Yimaitong specially invited Professor Li Ning of the Cancer Hospital of the Chinese Academy of Medical Sciences to share with us the current status and cutting-edge progress
in the diagnosis and treatment of platinum-resistant recurrent ovarian cancer.

- Professor Li Ning -

• Deputy Chief Physician of Department of Gynecologic Oncology, Cancer Hospital of Chinese Academy of Medical Sciences

• Vice Chairman of the Youth Committee of the Gynecologic Oncology Professional Committee of the Chinese Anti-Cancer Association

• Member of the Standing Committee of the Gynecologic Oncology Expert Committee of the Chinese Society of Clinical Oncology

• Youth member of the Gynecologic Oncology Professional Committee of the Chinese Medical Association

• Vice Chairman of the Gynecologic Oncology Expert Committee of Beijing Medical Award Foundation

• Member of the Standing Committee of the Clinical Oncology Committee of the Chinese Association of Women Physicians

• Member of the National Health Commission's Expert Committee on Capacity and Continuing Education Oncology

• Member of the first family hereditary tumor professional committee of the Chinese Anti-Cancer Association

Medical Pulse: Ovarian cancer is one of the three major malignant tumors of the
female reproductive system.
At present, the treatment of platinum-resistant recurrent ovarian cancer is still a major problem
.
Could you please briefly introduce the current status of diagnosis and treatment of platinum-resistant recurrent ovarian cancer in China? What treatment options are available for these patients?

Professor Li Ning

Cancer Hospital, Chinese Academy of Medical Sciences

The treatment of platinum-resistant/recurrent ovarian cancer patients has long been a clinical challenge, and although there are many treatment options available, the overall efficacy is not satisfactory
.
The objective response rate (ORR) of non-platinum monotherapy chemotherapy is about 20%, and even if the combination of anti-angiogenic drugs increases ORR to some extent, and the progression-free survival (PFS) is extended by two to three months, it does not meet the clinical needs
of platinum-resistant/recurrent ovarian cancer patients.
In addition to macromolecular monoclonal antibodies, small molecule tyrosine kinase inhibitors (TKIs) have also been tried in combination with cytotoxic drugs for platinum-resistant/recurrent ovarian cancer, and the results have shown that ORR and PFS can be improved, but there is still a considerable gap
to meet clinical needs.
Therefore, the search for new effective drugs for these patients is particularly urgent, and there are many new drugs currently being developed, and we look forward to bringing more treatment options
to patients with platinum-resistant/recurrent ovarian cancer.

Yimaitong: At this CSCO annual meeting, you reported on the phase Ib study of IN10018 combined with doxorubicin liposomes (PLD) in patients with platinum-resistant ovarian cancer.
What will be the boon for patients with platinum-resistant recurrent ovarian cancer?

Professor Li Ning

Cancer Hospital, Chinese Academy of Medical Sciences

IN10018 is a highly selective plaquekinase (FAK) inhibitor
independently developed in China.
Studies have shown that FAK inhibitors can overcome the fibrosis barrier of tumor stroma, have a significant impact on the tumor microenvironment, effectively reverse a variety of chemotherapy and targeted therapies caused by tumor drug resistance, and enhance the response and efficacy of solid tumors in the process of immunotherapy, so FAK is considered to be a very potential new anti-cancer drug target
。 FAK expression is upregulated in a variety of solid tumors, especially in ovarian cancer, up to 75% of ovarian cancer patients have FAK overexpression, amplification or activation, and the prognosis of such patients is worse, these findings provide a theoretical basis
for the application of FAK inhibitors in ovarian cancer.

The safety of IN10018 was explored in a previous phase I study, and the study showed that IN10018 had a good safety profile and showed a good efficacy in ovarian cancer, so the efficacy
of IN10018 in combination with chemotherapy was further explored in a dose-extension study 。 PLD is one of the chemotherapy regimens we often choose in the clinic for the treatment of platinum-resistant ovarian cancer, and preclinical PDX and CDX mouse models suggest that IN10018 combined with PLD can better exert anti-tumor effects, so we chose to evaluate the safety, tolerability and anti-tumor efficacy of IN10018 combined with PLD in patients with platinum-resistant recurrent ovarian cancer, and presented
at this CSCO meeting 。 The study currently enrolls a total of 50 patients with platinum-resistant recurrent ovarian cancer, with an ORR of 54.
8% and a median PFS of 7.
26 months
among 42 patients with evaluable efficacy.
In terms of safety, the most commonly reported adverse events (AEs) were proteinuria, fatigue, etc.
, most of which were grade 1 or 2, and the incidence of AEs above grade 3 did not exceed 10%, and overall, the safety and tolerability of combination therapy were good
.
The findings also suggest the need to further expand the study cohort, and a randomized controlled study of IN10018 plus PLD versus PLD plus placebo has been initiated
.
At present, only two FAK inhibitors in the world are in the clinical research and development stage, and IN10018, as an innovative drug independently developed by China, is at the leading level
in the world.

Yimaitong: There are a large number of unmet treatment needs in patients with platinum-resistant recurrent ovarian cancer, and more new treatment strategies
are still being explored.
Can you talk about what research directions are worth paying attention to?

Professor Li Ning

Cancer Hospital, Chinese Academy of Medical Sciences

In addition to FAK inhibitors, many new drugs with innovative mechanisms are being developed, including PARP inhibitors and antibody drug conjugates (ADCs).

In platinum-resistant ovarian cancer, ADC drug Mirvetuximab soravtansine has achieved gratifying results
both alone and in combination with bevacizumab.
The new dual-targeted-ligand conjugate drug CBP-1008 targeting FRa and TRPV6 has also been clinically studied in China, and preliminary results show that it has a significant effect, especially in patients with platinum-resistant ovarian cancer, and may become a new treatment option
for platinum-resistant ovarian cancer in the future.
In addition, new target drugs such as Wee1 kinase inhibitors and AKT kinase inhibitors are being developed at an accelerated pace, and combination drugs are the main research direction
.

Exploring combination therapy strategies based on existing drugs, such as PARP inhibitors combined with antiangiogenic drugs, and immune checkpoint inhibitors
, is also the focus of current research.
Since ovarian cancer is an immune desert tumor, the efficacy of immune checkpoint inhibitors in ovarian cancer is not outstanding, and the efficacy rate of immune monotherapy is less than 10%.

With the continuous exploration of immunocombination therapy strategies, it is expected to bring new hope
for platinum-resistant recurrent ovarian cancer in the future.

Edited by Faline

Reviewer: Professor Li Ning

Typesetting: Faline

Execution: Yuna

This platform is designed to deliver more medical information
to healthcare professionals.
The content published on this platform cannot replace professional medical guidance in any way, nor should it be regarded as diagnosis and treatment advice
.
If such information is used for purposes other than understanding medical information, this platform does not assume relevant responsibilities
.
The content published by this platform does not mean that it agrees with its description and views
.
If copyright issues are involved, please contact us and we will deal with
it as soon as possible.