On April 1, 2024 Zai Lab Limited (NASDAQ: ZLAB; HKEX: 9688) partner Bristol Myers Squibb (NYSE: BMY) reported the pivotal Phase 3 KRYSTAL-12 study, evaluating KRAZATI (adagrasib) as a monotherapy in patients with pretreated locally advanced or metastatic non-small cell lung cancer (NSCLC) harboring a KRASG12C mutation, met the primary endpoint of progression-free survival (PFS) and the key secondary endpoint of overall response rate (ORR) as assessed by Blinded Independent Central Review (BICR) at final analysis for these endpoints (Press release, Zai Laboratory, APR 1, 2024, View Source; [SID1234641684]). The study remains ongoing to assess the additional key secondary endpoint of overall survival. Results of the confirmatory trial showed that KRAZATI demonstrated a statistically significant and clinically meaningful benefit in PFS and ORR compared to standard-of-care chemotherapy as a second-line or later treatment for these patients. KRAZATI had no new safety signals and the safety data was consistent with the known safety profile.

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"We are delighted to see these data underscoring the potential of adagrasib as a therapy for patients with KRASG12C mutated NSCLC in second or later line treatment," said Rafael G. Amado, M.D., President, Head of Global Oncology Research and Development, Zai Lab. "Lung cancer is the most common cancer in China, and adagrasib is one of several important products in Zai Lab’s growing lung cancer pipeline. We are proud to have contributed to the KRYSTAL-12 study and are looking forward to bringing adagrasib to patients in need in China."

Bristol Myers Squibb will complete a full evaluation of the available data and will share the results with the scientific community at an upcoming medical conference as well as discuss the results with health authorities.

Zai Lab expects to submit the New Drug Application (NDA) for adagrasib to the National Medical Products Association (NMPA) for KRASG12C mutated NSCLC in second or later line treatment in China this year.

In addition to KRASG12C-mutated NSCLC, KRAZATI and KRAZATI-based combinations have shown encouraging meaningful benefit in Phase 2 clinical trials across several tumors, including advanced colorectal cancer, pancreatic cancer and other solid tumors. In February, the U.S. FDA accepted for priority review the supplemental new drug application (sNDA) for KRAZATI in combination with cetuximab for the treatment of patients with previously treated KRASG12C-mutated locally advanced or metastatic colorectal cancer (CRC). The FDA assigned a Prescription Drug User Fee Act (PDUFA) goal date of June 21, 2024.

Zai Lab thanks the patients and investigators involved in the KRYSTAL-12 clinical trial.

About NSCLC in China
According to the World Health Organization, the incidence of lung cancer in China in 2020 was 815,563 cases, with 714,699 deaths. Lung cancer consists of NSCLC in approximately 85% of cases and small cell lung cancer (SCLC) in approximately 15% of cases. KRASG12C is the most common KRAS mutation in NSCLC. The mutation is a biomarker of poor prognosis in Chinese patients with NSCLC.

ABOUT KRAZATI (adagrasib)
KRAZATI (adagrasib) is highly selective and potent oral small-molecule inhibitor of KRASG12C that is optimized to sustain target inhibition, an attribute that could be important to treat KRASG12C-mutated cancers, as the KRAS protein regenerates every 24-48 hours. In China, it is estimated that there are around 42,000 patients each year with KRASG12C-mutated NSCLC and colorectal cancer indications alone.

In 2022, KRAZATI was granted accelerated approval for treatment of adult patients with KRASG12C-mutated locally advanced or metastatic NSCLC, as determined by an FDA-approved test, who have received at least one prior systemic therapy. This indication is approved under accelerated approval based on objective response rate (ORR) and duration of response (DOR). Continued approval for this indication may be contingent upon verification and description of a clinical benefit in a confirmatory trial(s).

In 2023, Medicines and Healthcare products Regulatory Agency (MHRA) granted conditional marketing authorization for KRAZATI as a targeted treatment option for adult patients with KRASG12C-mutated advanced non-small cell lung cancer and disease progression after at least one prior systemic therapy followed by the European Commission (EC) in 2024.

KRAZATI continues to be evaluated as monotherapy and in combination with other anti-cancer therapies in patients with advanced KRASG12C-mutated solid tumors, including non-small cell lung cancer and colorectal cancer.

In 2022, the FDA granted breakthrough therapy designation for KRAZATI in combination with cetuximab in patients with KRASG12C-mutated advanced colorectal cancer whose cancer has progressed following prior treatment with chemotherapy and an anti-VEGF therapy.

For U.S. Prescribing Information, visit KRAZATI.

About KRYSTAL-12
KRYSTAL-12 is an open-label, multicenter, randomized Phase 3 study evaluating KRAZATI compared to standard-of-care chemotherapy alone, in patients with KRASG12C-mutated non-small cell lung cancer. The primary endpoint of the study is PFS as assessed by BICR. Secondary endpoints included overall survival (OS), overall response rate (ORR), duration of response (DOR), and safety.