◆ The ORR (objective response rate) and the DCR (disease control rate) in the frontline setting of glecirasib (KRAS G12C Inhibitor) in combination with JAB-3312 (SHP2 inhibitor) were 65.5% (38/58) and 100% respectively in all dose groups of advanced non-small cell lung cancer (NSCLC), among which, in the dose group of 800 mg glecirasib (once daily) in combination with 2 mg JAB-3312 (once daily for 1 week on, then 1 week off), the ORR was 86.7% (13/15), and the DCR was 100%.
◆ The results of this clinical trial validated the safety and efficacy of the combination therapy of glecirasib and JAB-3312, which laid a foundation for a further registrational clinical trial.
Beijing, Madrid, Oct 22, 2023— Jacobio Pharma (1167.HK), a clinical-stage oncology company focusing on undruggable targets, is pleased to announce that the clinical data of glecirasib in combination with JAB-3312 was published in the form of a proffered paper presentation at the 2023 European Society for Medical Oncology Congress (ESMO 2023).
Jacobio presented results of a Phase I/IIa study of glecirasib in combination with JAB-3312. The trial consisted of seven dose groups, including glecirasib of 400 mg and 800 mg in combination with JAB-3312 at different doses and dosing intervals, aiming to explore the safety, efficacy, and tolerability through different dose groups, and to provide a basis for a subsequent registrational clinical trial. As of August 4, 2023, a total of 144 KRAS G12C mutant patients were enrolled, including 129 NSCLC patients, 14 patients with colorectal cancer, and 1 patient with pancreatic cancer.
Among the 129 NSCLC (non-small cell lung cancer) patients involved in the trial, 107 patients had undergone at least one tumor assessment using RECIST1.1 criteria, and 58 of them were first-line therapy patients (spread across the seven dose groups), with an ORR of 65.5% (38/58) and a DCR of 100%. The ORR was 86.7% (13/15) in the dose group of 800 mg glecirasib in combination with 2 mg JAB-3312. The mPFS (median progression-free survival) and duration of response are still under observation as the patients are still undergoing treatment.
The incidence of grades 3 and 4 TRAEs (treatment-related adverse events) was 39.6% across all the dose groups, whereas the incidence of grades 3 and 4 TRAEs was 36.7% in the dose group  of 800 mg glecirasib in combination with 2 mg JAB-3312.
Relevant studies have shown that the SHP2 inhibitor is one of the most promising drug partners for the KRAS G12C inhibitor in NSCLC.
"In KRAS G12C mutant NSCLC patients, the combination therapy of glecirasib with JAB-3312 has shown positive efficacy signals. Compared with monotherapy, combination therapy can synergistically inhibit tumor growth. In addition, both drugs are administered orally, so patients do not need to be hospitalized, which is more convenient for patients,” said Prof. Jie WANG from the Cancer Hospital, Chinese Academy of Medical Sciences, the principal investigator of this trial. "We look forward to further validating the clinical efficacy of the combination therapy through follow-up studies.”
“The data provides the basis for the registrational clinical study of glecirasib in combination with SHP2 inhibitor. The research team will determine the following registrational clinical trial plan based on the optimal dose combination of this trial after the PFS data matures,” said Andrea WANG-GILLAM M.D., Ph.D., Chief Medical Officer of Jacobio. “SHP2 is a target for which there are no approved or marketed inhibitors anywhere in the world. We hope that through this study, we can bring confidence to SHP2 inhibitor investigators, improve the response rate of the KRAS G12C inhibitor as monotherapy, prolong patients' survival periods, and improve their quality of life.”
 Once daily for 1 week on, then 1 week off.
For more information, please visit the official website of ESMO: https://www.esmo.org/.
Conference Call Information
Jacobio will host a live conference call on Oct. 24, 2023, at 14:00-15:00 (UTC+8). Participants must register in advance of the conference call. Registration Link: https://goldmansachs.zoom.us/webinar/register/WN_6sS33tpzRMWy2vFSPSx11Q
Glecirasib is a KRAS G12C inhibitor developed by Jacobio. A number of Phase I/II clinical trials of glecirasib are currently ongoing in China, the United States and Europe for patients with advanced solid tumors harboring KRAS G12C mutation. These include a pivotal clinical trial in NSCLC in China; a monotherapy study for STK11 co-mutated NSCLC in the front-line setting, and combination therapy trials with SHP2 inhibitor JAB-3312 in NSCLC and with Cetuximab in colorectal cancer.
JAB-3312 is a highly selective SHP2 allosteric inhibitor with best-in-class potential. Jacobio is currently conducting clinical trials of JAB-3312 in monotherapy and combination therapies with glecirasib and other agents in China, the United States and Europe.
Jacobio Pharma (1167.HK) is committed to developing and providing new and innovative products and solutions to improve people's health. Our pipeline revolves around novel molecular targets on six major signaling pathways: KRAS, immune checkpoints, tumor metabolism, P53, RB and MYC. We aim for our key projects to be among the top three in the world. Our vision is to become a global leader recognized for our impact in drug R&D together with our partners. Jacobio has R&D centers in Beijing, Shanghai and Boston with our Induced Allosteric Drug Discovery Platform (IADDP) and our iADC Platform.