On November 2, 2023 Kura Oncology, Inc. (NASDAQ: KURA), a clinical-stage biopharmaceutical company committed to realizing the promise of precision medicines for the treatment of cancer, and Mirati Therapeutics, Inc. (NASDAQ: MRTX), a commercial-stage targeted oncology company, reported a clinical collaboration and supply agreement to evaluate the combination of KO-2806, a next-generation farnesyl transferase inhibitor (FTI), and adagrasib, a highly selective KRASG12C inhibitor, in patients with KRASG12C-mutated non-small cell lung cancer (NSCLC) (Press release, Kura Oncology, NOV 2, 2023, View Source [SID1234636815]).

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"Recent findings suggest that combining KO-2806 with adagrasib can drive tumor regressions and enhance both duration and depth of antitumor response in preclinical models of KRASG12C-mutated NSCLC," said Stephen Dale, M.D., Chief Medical Officer of Kura Oncology. "This collaboration highlights the potential to address the urgent need for more durable and effective treatment options for patients with advanced solid tumors, and we look forward to collaborating with Mirati, an established leader in targeted oncology."

"We are pleased to collaborate with Kura Oncology on this clinical study of KO-2806 with adagrasib. Preclinical work demonstrates the ability of adagrasib, in combination with a FTI, to improve patient outcomes," said Alan Sandler, M.D., Chief Medical Officer, Mirati Therapeutics. "This collaboration exemplifies the potential combinability of adagrasib as a key differentiation from other KRASG12C inhibitors."

Under the terms of the agreement, Kura will sponsor the Phase 1 study of KO-2806 and adagrasib in patients with KRASG12C-mutated NSCLC. Mirati will supply Kura with adagrasib for the study.

About KO-2806

KO-2806 is a next-generation inhibitor of farnesyl transferase designed to improve upon potency, pharmacokinetic and physicochemical properties of earlier FTI drug candidates. Earlier this year, Kura received FDA clearance of its Investigational New Drug application for KO-2806. In addition to KRASG12C NSCLC, KO-2806 has demonstrated encouraging preclinical activity in clear cell renal cell carcinoma (ccRCC). The Company recently dosed the first patients in a Phase 1 dose-escalation trial of KO-2806 (FIT-001). Concurrent with dose escalation as a monotherapy, Kura also plans to evaluate KO-2806 in dose-escalation combination cohorts with other targeted therapies in advanced solid tumors, including adagrasib in KRASG12C-mutated NSCLC and a tyrosine kinase inhibitor in ccRCC.

About Adagrasib

Adagrasib is being evaluated as monotherapy and in combination with other anti-cancer therapies in patients with advanced KRASG12C-mutated solid tumors, including NSCLC, colorectal cancer, and pancreatic cancer. For more information, visit Mirati.com/science.

KRAZATI (adagrasib) U.S. Indication

KRAZATI is indicated for the treatment of adult patients with KRASG12C-mutated locally advanced or metastatic non-small cell lung cancer (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). For Prescribing Information, visit Mirati.com/KRAZATI_USPI.

KRAZATI (adagrasib) Important Safety Information

WARNINGS AND PRECAUTIONS

Gastrointestinal Adverse Reactions

In the pooled safety population, serious gastrointestinal adverse reactions observed were gastrointestinal obstruction in 1.6%, including 1.4% grade 3 or 4, gastrointestinal bleeding in 0.5% of patients, including 0.5% grade 3, and colitis in 0.3%, including 0.3% grade 3. In addition, nausea, diarrhea, or vomiting occurred in 89% of 366 patients, including 9% grade 3. Nausea, diarrhea, or vomiting led to dosage interruption or dose reduction in 29% of patients and permanent discontinuation of KRAZATI in 0.3%
Monitor and manage patients using supportive care, including antidiarrheals, antiemetics, or fluid replacement, as indicated. Withhold, reduce the dose, or permanently discontinue KRAZATI based on severity
QTc Interval Prolongation

KRAZATI can cause QTc interval prolongation, which can increase the risk for ventricular tachyarrhythmias (eg, torsades de pointes) or sudden death
In the pooled safety population, 6% of 366 patients with at least one post-baseline electrocardiogram (ECG) assessment had an average QTc ≥501 ms, and 11% of patients had an increase from baseline of QTc >60 msec. KRAZATI causes concentration-dependent increases in the QTc interval
Avoid concomitant use of KRAZATI with other products with a known potential to prolong the QTc interval. Avoid use of KRAZATI in patients with congenital long QT syndrome and in patients with concurrent QTc prolongation
Monitor ECGs and electrolytes prior to starting KRAZATI, during concomitant use, and as clinically indicated in patients with congestive heart failure, bradyarrhythmias, electrolyte abnormalities, and in patients who are taking medications that are known to prolong the QT interval. Withhold, reduce the dose, or permanently discontinue KRAZATI, depending on severity
Hepatotoxicity

KRAZATI can cause hepatotoxicity
In the pooled safety population, hepatotoxicity occurred in 37%, and 7% were grade 3 or 4. A total of 32% of patients who received KRAZATI had increased alanine aminotransferase (ALT)/increased aspartate aminotransferase (AST); 5% were grade 3 and 0.5% were grade 4. Increased ALT/AST leading to dose interruption or reduction occurred in 11% of patients. KRAZATI was discontinued due to increased ALT/AST in 0.5% of patients
Monitor liver laboratory tests (AST, ALT, alkaline phosphatase, and total bilirubin) prior to the start of KRAZATI, and monthly for 3 months or as clinically indicated, with more frequent testing in patients who develop transaminase elevations. Reduce the dose, withhold, or permanently discontinue KRAZATI based on severity
Interstitial Lung Disease /Pneumonitis

KRAZATI can cause interstitial lung disease (ILD)/pneumonitis, which can be fatal. In the pooled safety population, ILD/pneumonitis occurred in 4.1% of patients, 1.4% were grade 3 or 4, and 1 case was fatal. The median time to first onset for ILD/pneumonitis was 12 weeks (range: 5 to 31 weeks). KRAZATI was discontinued due to ILD/pneumonitis in 0.8% of patients
Monitor patients for new or worsening respiratory symptoms indicative of ILD/pneumonitis (eg, dyspnea, cough, fever). Withhold KRAZATI in patients with suspected ILD/pneumonitis and permanently discontinue KRAZATI if no other potential causes of ILD/pneumonitis are identified
Adverse Reactions

The most common adverse reactions (≥25%) are nausea, diarrhea, vomiting, fatigue, musculoskeletal pain, hepatotoxicity, renal impairment, edema, dyspnea, decreased appetite
Females and Males of Reproductive Potential

Infertility: Based on findings from animal studies, KRAZATI may impair fertility in females and males of reproductive potential
Please see Full Prescribing Information.