Allist’s Furmonertinib Monotherapy Study Showcases Promising Results in First-Line Treatment of EGFR PACC Mutant NSCLC

On September 9, ArriVent BioPharma and Allist Pharmaceuticals unveiled groundbreaking data from their global Phase Ib proof-of-concept randomized study (FURTHER) at the IASCLC 2024 World Conference on Lung Cancer (WCLC). Conducted on patients with EGFR PACC mutant non-small cell lung cancer (NSCLC), the study focused on the efficacy of Furmonertinib as a first-line monotherapy.

In the 240mg QD dosing group, the best objective response rate (ORR) assessed by a blinded independent central review (BICR) was an impressive 81.8%, with a confirmed ORR (cORR) of 63.6%. Among patients with central nervous system (CNS) metastases, the cORR was 46.2%. Notably, 90.9% (n=20/22) of patients who had shown a confirmed response remained in the study, with the median duration of response (DoR) yet to be reached at the time of data analysis.

About the Phase Ib FURTHER Trial

Furmonertinib is an oral, once-daily, third-generation EGFR tyrosine kinase inhibitor (TKI) with strong CNS penetration and broad activity against EGFR mutations. The Phase Ib FURTHER trial evaluated its preliminary clinical efficacy and safety profile as a first-line treatment for EGFR PACC mutant NSCLC, yielding the following key results:

1. First Global Multi-Center Randomized Study: This is the first global multi-center randomized clinical study evaluating a third-generation EGFR-TKI specifically for EGFR PACC mutant NSCLC patients.

2. Significant Systemic and CNS Responses By June 20, 2024:

- The BICR-assessed ORR for the 240mg QD and 160mg QD dosing groups were 81.8% and 47.8%, respectively.

-The BICR-confirmed ORR (cORR) for the 240mg QD and 160mg QD dosing groups were 63.6% and 34.8%, respectively, with one unconfirmed partial response (PR) in each dosing group awaiting confirmation.

- The median duration of response (DoR) was yet to be reached; 90.9% (n=20/22) of patients with confirmed responses were still under study.

- In first-line patients with baseline brain metastases, the CNS ORR determined by BICR-RECIST 1.1 was 46.2% (n=6/13).

3. Good Tolerability: The treatment was generally well-tolerated, consistent with prior Furmonertinib data.

- Common treatment-related adverse events (TRAEs) included diarrhea, rash, dry skin, stomatitis, and elevated liver enzymes.

- No discontinuations due to TRAEs were observed.

Furmonertinib has shown dose-dependent activity in treating metastatic EGFR PACC mutant NSCLC, including significant CNS anti-tumor activity consistent with its high CNS penetrance capabilities.

About Furmonertinib

Furmonertinib is a selective EGFR inhibitor with high oral bioavailability and CNS permeability, effective against both common and rare EGFR mutations, including PACC and Exon20ins. It was approved in March 2021 for the second-line treatment of adult patients with locally advanced or metastatic NSCLC who have progressed on prior EGFR TKI therapy and have confirmed EGFR T790M mutations. In June 2022, it received approval for the first-line treatment of adult patients with locally advanced or metastatic NSCLC harboring EGFR exon 19 deletions or exon 21 L858R substitution mutations. Both indications are now covered under the national health insurance reimbursement scheme.

In the first half of 2024, Furmonertinib achieved a revenue of 1.555 billion RMB, with total cumulative revenue reaching 4.558 billion RMB since its launch. In June 2021, Allist entered into an exclusive overseas licensing agreement with ArriVent Biopharma, Inc. Under this agreement, ArriVent holds exclusive rights to develop and commercialize Furmonertinib outside of Mainland China, Hong Kong, Macau, and Taiwan, while Allist retains these rights within these regions. The agreement includes a $40 million upfront payment to Allist, along with equity in ArriVent and potential milestone payments up to $765 million, in addition to double-digit percentage royalties on sales.

About EGFR-TKI

EGFR inhibitors function by competitively binding to the epidermal growth factor receptor (EGFR), thereby blocking EGFR's interaction with adenosine triphosphate (ATP) and inhibiting its activation. This disruption leads to the inhibition of downstream signaling pathways, ultimately preventing tumor cell proliferation. EGFR has now become one of the primary targets for the treatment of non-small cell lung cancer (NSCLC), with approximately 40% of Chinese NSCLC patients harboring EGFR-sensitive mutations.

Currently, there are three generations of epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs). The primary resistance mechanisms for first- and second-generation EGFR inhibitors include the T790M mutation and other alterations such as MET amplification. The third-generation EGFR inhibitors are specifically developed to target the T790M mutation and possess a molecular framework that is entirely different from the first and second generations. These inhibitors can overcome T790M resistance mutations, significantly enhancing their ability to inhibit tumor cells.

AstraZeneca’s Osimertinib has effectively addressed the T790M resistance problem, successfully extending the overall survival time of lung cancer patients to 38.6 months, thereby becoming a mainstream EGFR-TKI. With a revenue of $5.799 billion in 2023 and a sales figure of $3.203 billion in the first half of this year alone—a 13% increase compared to the previous year—Osimertinib ranks fifth in global oncology drug sales for the first half of 2024.

The Challenge from Allist Pharma

Allist Pharma's confidence comes from a series of preliminary research data. For Furmonertinib, initiating such an international multi-center randomized controlled clinical trial to directly compare itself with Osimertinib demonstrates significant courage, deserving respect from all in the pharmaceutical community. Of course, we eagerly anticipate the subsequent clinical progress and hope that it can mark another glorious moment in the history of innovative drugs in China.

About EGFR PACC Mutation

The concept of the EGFR PACC mutation was first proposed by the MD Anderson Cancer Center in a 2021 Nature publication titled "Structure-based classification predicts drug response in EGFR-mutant NSCLC." Researchers classified EGFR mutations based on drug sensitivity and structural changes into classic mutations, T790M mutations, Exon20ins mutations, and PACC mutations. EGFR-PACC mutations occur in exons 18-21 and include G719X, L747X, S768I, L792X, and T854I mutations, accounting for approximately 12% of EGFR mutations. Globally, over 80,000 new patients with EGFR PACC-mutant NSCLC are diagnosed annually, and there are currently no approved effective treatments for these mutations. Furmonertinib, as the first third-generation EGFR-TKI to show clinical benefit for patients with EGFR PACC mutations, has the potential to become the first approved drug for this indication.

About Allist Pharma

Founded in 2004, Allist Pharma is an innovative drug company focused on addressing unmet clinical needs for patients worldwide. The company has successfully developed and received approval for two first-in-class new drugs: Allisartan (transferred to Salubris in 2012) and Furmonertinib Mesylate Tablets.

In the first half of 2024, Allist Pharma achieved total revenue of 1.576 billion RMB, a 110.57% year-on-year increase, primarily due to the inclusion of Furmonertinib Mesylate Tablets’ first-line treatment indication into the medical insurance scheme. As a result, sales volume continued to grow steadily, with the market share gradually increasing. Furmonertinib generated 1.555 billion RMB in revenue for the first half of 2024. The company’s net profit attributable to shareholders was 656 million RMB, a 214.82% year-on-year increase; excluding non-recurring gains and losses, the net profit amounted to 647 million RMB, a 251.94% year-on-year increase. These substantial profit gains were achieved through effective cost control in conjunction with significant revenue growth. 

In addition to Furmonertinib, Allist Pharma is also advancing KRAS G12D inhibitor AST2169 to Phase I clinical research. The KRAS G12D mutation is a common subtype of KRAS mutations, present in various cancer types, including NSCLC, colorectal cancer, and pancreatic cancer. Currently, no KRAS G12D inhibitors are approved globally. 

To further expand its oncology R&D pipeline, on August 30, Allist Pharma signed a strategic collaboration agreement with Jacobio Pharmaceuticals, acquiring the exclusive rights in China to research, develop, produce, register, and commercialize Jacobio's KRAS G12C inhibitor Glecirasib.

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