• 02 Apr 2024
• Admin
• News Article

Bristol Myers Squibb’s KRYSTAL-12 for Krazati Meets Primary Endpoint

"Bristol Myers Squibb’s pivotal KRYSTAL-12 study of Krazati meets primary endpoint of PFS for patients with pretreated KRAS G12C-mutated locally advanced or metastatic NSCLC

Overview 

Bristol Myers Squibb announced that 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) harbouring 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. The study remains ongoing to assess the additional key secondary endpoint of overall survival.

Outcome

• 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.

Words from Bristol Myers Squibb

“Today’s news is an important reinforcement of the power of a targeted therapy for patients with locally advanced or metastatic KRASG12C-mutated lung cancer. FDA approval of Krazati in the US has allowed us to provide a new treatment option for these patients, and topline results of the KRYSTAL-12 confirmatory study will build greater trust in the medical and patient community,” said Abderrahim Oukessou, M.D., vice president, global programme lead, Krazati, Bristol Myers Squibb. “We are encouraged by the results from KRYSTAL-12 and look forward to helping more patients with KRASG12C-mutated lung cancer.”

Future Evaluation

The company will complete a full evaluation of the available data and looks forward to sharing the results with the scientific community at an upcoming medical conference as well as discussing the results with health authorities.

FDA Approval

• The US FDA granted accelerated approval for Krazati as a targeted treatment for patients with KRASG12C-mutated locally advanced or metastatic NSCLC who have received at least one prior systemic therapy in December 2022. 
• 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 NSCLC and disease progression after at least one prior systemic therapy followed by the European Commission (EC) in 2024.

Phase II Responses

• In addition to KRASG12C-mutated NSCLC, Krazati and Krazati-based combinations have shown encouraging meaningful benefit in phase 2 clinical trials across several tumours, including advanced colorectal cancer, pancreatic cancer and other solid tumours. 
• In February, the US 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.

Bristol Myers Squibb thanks the patients and investigators involved in the KRYSTAL-12 clinical trial.

About Krazati

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. 

KRASG12C mutations act as oncogenic drivers and occur in approximately 14% of non-small cell lung cancer, 3-4% of colorectal cancer, and 1-2% of several other cancers.

Approvals 

• 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).

MHRA Authorization

• 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.

Indication

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

BTD

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.

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.

Other Uses

• Krazati is indicated for the treatment of adult patients with KRASG12C-mutated locally advanced or metastatic non-small cell lung cancer, 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).

Bristol Myers Squibb: Vision

• Bristol Myers Squibb is inspired by a single vision — transforming patients’ lives through science. The goal of the company’s cancer research is to deliver medicines that offer each patient a better, healthier life and to make cure a possibility. 
• Building on a legacy across a broad range of cancers that have changed survival expectations for many, Bristol Myers Squibb researchers are exploring new frontiers in personalized medicine, and through innovative digital platforms, are turning data into insights that sharpen their focus. 
• Deep understanding of causal human biology, cutting-edge capabilities and differentiated research programs uniquely position the company to approach cancer from every angle. 
• Cancer can have a relentless grasp on many parts of a patient’s life, and Bristol Myers Squibb is committed to taking actions to address all aspects of care, from diagnosis to survivorship. 
• As a leader in cancer care, Bristol Myers Squibb is working to empower all people with cancer to have a better future.
• Bristol Myers Squibb is a global biopharmaceutical company whose mission is to discover, develop and deliver innovative medicines that help patients prevail over serious diseases.