CSCO2021 Professor Li Jin: New hope for HER2-positive solid tumors, Phase I study of new ADC drug MRG002 announced

On September 25-29, 2021, the 24th National Conference on Clinical Oncology and the 2021 CSCO Academic Annual Meeting will be held as scheduled to promote the continuous development of China's oncology field
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The HER2 target is very mature in the development of solid tumors, and its precise treatment has also been innovated with the progress of clinical research
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On the first day of the conference, the MRG002 phase I study led by Professor Li Jin from Dongji University Affiliated Hospital (Shanghai Dongfang Hospital) detonated anti-HER2 diagnosis and treatment hotspots.
From HER2-positive gastric cancer to breast cancer, the new ADC drug MRG002 initially demonstrated the efficacy and safety , Ignite new hope for patients
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On September 25, 2021, in the main venue on the first day of the CSCO Academic Annual Conference, Professor Li Jin, the chairman of the CSCO Conference, Dongji University Affiliated Oriental Hospital (Shanghai Oriental Hospital), issued the title "Evaluation of Recombinant Humanized Anti-HER2 Monoclonal Antibody for Injection" -MMAE conjugate (MRG002) in patients with HER2-positive advanced solid tumors, the safety, tolerability, dose escalation and expansion of clinical research" important report, for the development of anti-HER2 ADC drugs in China painted a strong color One stroke
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On behalf of the clinical trial team, Professor Li Jin expressed his gratitude to the conference for selecting this study as the keynote venue report, and then reviewed the background of the rapid development of ADC drugs in recent years, which are gradually becoming a new choice for the treatment of HER2-positive solid tumors
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ADC drugs are known as "magic bullets" and continue to expand their boundaries in solid tumors
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MRG002 is an emerging ADC drug independently developed in my country.
Professor Li Jin said that “its design is very clever”.
From the structure and mechanism point of view, its sugar-modified trastuzumab through the enzyme-cleavable vc linker and MMAE (methyl Australian Rstatin E) conjugated, and its chemotherapy part, MMAE, is a tubulin inhibitor widely used in ADC at present.
It can inhibit the polymerization of microtubules, interfere with mitosis and cause cell death.
It is "a powerful enough cytotoxic drug"
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Professor Li Jin emphasized that "The MRG002 linker is different from other ADCs.
It is a cleavable vc linker, which is more prone to bystander effect.
" This linker is stable enough in the blood and will be quickly cleaved after being internalized into the lysosome.
, The rapid release of MMAE molecules, and then the formation of the bystander effect, so that the anti-tumor effect is more prominently embodied, and it is a promising ADC drug in the current tumor field
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On the basis of fully analyzing the structure and mechanism of MRG002, Professor Li Jin announced the progress of the phase I clinical study of MRG002 applied to HER2-positive advanced solid tumors.
The study was led by Shanghai Dongfang Hospital affiliated to Tongji University and participated by 9 centers across the country.
On July 30, 2021, a total of 76 patients were enrolled, and they were divided into two stages: dose escalation (Ia) and dose expansion (Ib)
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25 patients in the phase Ⅰa dose escalation stage received 0.
3, 0.
6, 1.
2, 1.
8, 2.
2, 2.
6, 3.
0 mg/kg Q3W MRG002 treatment, covering breast cancer, parotid gland cancer, and gastric cancer
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Among 22 patients with evaluable solid tumors in Ia, 88% have received HER2 targeted therapy, the median number of previous treatment lines was 5, the overall ORR was 45%, the DCR was 82%, and the median PFS was 7.
4 months
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Mentioning this, Professor Li Jin believes: “For patients who have failed multi-line therapy, they can still obtain such a long PFS, and the prospects are promising!” In the safety results, Professor Li Jin pointed out that common adverse events are cytotoxic drugs.
The associated leukopenia and liver function effects are generally safe and tolerable
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Based on the efficacy and safety, the recommended dose at this stage is initially 2.
6 mg/kg (RP2D)
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The 51 patients enrolled in the phase Ⅰb dose expansion phase were studied with 2.
6mg/kg MRG002, covering breast cancer and gastric cancer.
The previous median systemic treatment was 5 lines, and 99% of the patients had previously received anti-her2 therapy.

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Among the 43 evaluable patients, 22 were PR, 18 were SD, and 3 were PD, with an ORR of 51% and a DCR of 93%; 2 PRs were observed in 6 patients who failed the previous T-DM1 treatment; another 8 patients are still taking medication, and Professor Li Jin has high hopes for the follow-up observation results
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Professor Li Jin further analyzed the effect of MRG002 on HER2-positive breast cancer and gastric cancer in the entire phase I study
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Among the 5 evaluable patients with trastuzumab-resistant gastric cancer who had previously received 2-line therapy, the ORR was 60% and the DCR was 80%
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Among the 47 evaluable HER2-positive breast cancers with doses above RP2D, the ORR reached 53%.
Among them, the ORR of 23 patients with liver metastasis was 61%, the ORR of 5 patients with liver+brain metastasis was 60%, and 22 patients with HER2 and HR double positive The ORR of sexual patients is 68%
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Regarding the safety of the Phase Ib study, the common adverse reactions were decreased neutrophil count (46%), increased LDH (43%), mostly grade 1 to 2; common (incidence rate ≥10%) grade 3 The only adverse reaction was a decrease in neutrophil count (17%), and there were no life-threatening adverse events
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Based on this, Professor Li Jin assessed: "The safety of MRG002 is very good, the adverse reactions are controllable and can return to normal in a short time
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" The preliminary results of the study have been announced at this year's ESMO meeting.
The anti-tumor activity and controllable safety and tolerability of the HER2-positive advanced solid tumor patient population have been widely recognized
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Professor Li Jin concluded that MRG002 has initially shown the efficacy of posterior treatment in HER2-positive gastric cancer and breast cancer, providing a new direction for clinical treatment, but it still needs to be further explored in the subsequent phase II and phase III studies.
Sex and safety
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After Professor Li Jin's explanation, under the auspices of Professor Guo Jun from Peking University Cancer Hospital, Professor Liang Jun and Professor Li Jin from Peking University International Hospital discussed the safety and drug resistance of ADC drugs
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Professor Li Jin pointed out that due to the characteristics of ADC drug targeted chemotherapy, it is safer than chemotherapy alone; however, in terms of drug resistance, drug resistance has been found in the first-line and second-line medications of ADC drugs currently on the market.
For MRG002, the current research is still at the median 5-line treatment line sequence, and no drug resistance has been observed for the time being.
It is hoped that the follow-up line sequence advancement research will be able to carry out related explorations
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At the end of this session, Professor Li Jin called on oncologists across the country to work together to speed up the process of follow-up trials, especially in the field of gastric cancer and breast cancer, to help MRG002 go on the market as soon as possible, and bring more choices and more benefits to patients
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