Updated Data from the Phase 1/2 Study of Olomorasib in KRAS G12C-Mutant Advanced Solid Tumors Presented at the 2024 ASCO® Annual Meeting
Eli Lilly has released updated data from the Phase 1/2 clinical trial of olomorasib, an investigational second-generation KRAS G12C inhibitor. The data, presented at the 2024 ASCO Annual Meeting, showed promising efficacy and tolerability in patients with KRAS G12C-mutant advanced solid tumors, including NSCLC. Olomorasib demonstrated an objective response rate (ORR) of 35% across non-CRC solid tumors and 41% in NSCLC patients previously treated with a KRAS G12C inhibitor. In combination with pembrolizumab, the ORR for first-line metastatic NSCLC was 77%. Common treatment-related adverse events (TRAEs) were mostly mild, with diarrhea, nausea, and fatigue being the most frequent. The study also highlighted preliminary CNS activity in NSCLC patients with brain metastases. Eli Lilly aims to further investigate olomorasib in combination therapies for first-line NSCLC through the ongoing SUNRAY-01 trial.
- Olomorasib showed a 35% ORR across non-CRC solid tumors.
- In NSCLC patients previously treated with KRAS G12C inhibitors, olomorasib had a 41% ORR.
- Olomorasib in combination with pembrolizumab resulted in a 77% ORR for first-line metastatic NSCLC.
- Median progression-free survival was 7.1 months for KRAS G12C inhibitor-naive non-CRC tumors.
- Preliminary CNS activity observed in NSCLC patients with measurable brain metastases.
- Low discontinuation rate due to TRAEs: 1% for olomorasib monotherapy, 3% for combination therapy.
- Median treatment duration was 4.7 months, indicating a potential need for longer-term efficacy data.
- Patients experienced common TRAEs including diarrhea (23%), nausea (11%), and fatigue (10%).
- TRAEs led to the discontinuation of pembrolizumab in 11% of patients when combined with olomorasib.
- Concerns about the duration of follow-up in combination therapy, as median PFS was not reached.
Insights
Evaluating the updated Phase 1/2 clinical trial data for olomorasib, the findings highlight two critical points: the drug's efficacy across various KRAS G12C-mutant solid tumors and its potential synergistic effect when combined with pembrolizumab for NSCLC.
The observed Objective Response Rates (ORR) of 35% in non-CRC solid tumors and 41% in NSCLC patients previously treated with a KRAS G12C inhibitor are promising. A median Progression-Free Survival (PFS) of 7.1 months for non-CRC tumors and 8.1 months for previously treated NSCLC patients further underscores olomorasib's potential.
The news about preliminary CNS activity is especially noteworthy, considering the challenge of treating brain metastases. However, the data should be interpreted cautiously, as it is still in early stages.
In terms of safety, the tolerability of olomorasib, even in second-generation, appears acceptable with mostly Grade 1 TRAEs like diarrhea, nausea and fatigue. The low discontinuation rates (1%) due to adverse events are favorable, indicating a manageable safety profile.
For retail investors, this data provides a positive provisional outlook on olomorasib's development. If further confirmed in later stages, the drug could significantly impact treatment protocols for KRAS G12C-mutant cancers.
From a clinical perspective, the data on olomorasib provides several insights. The combination with pembrolizumab showcased an impressive ORR of 77% in first-line metastatic NSCLC patients, which is higher than many existing treatments. This highlights the drug's potential efficacy in enhancing immunotherapy regimens.
The lack of reached median PFS in the combination therapy group suggests durable responses, but longer follow-ups are essential for a more definitive conclusion. Encouragingly, the combination therapy's safety profile, with low discontinuation rates (only 5% for both drugs), is a substantial positive, suggesting patients can maintain therapy without severe side effects.
The continuation of the SUNRAY-01 trial is crucial, as it will provide larger-scale data to verify these preliminary results. Retail investors should watch for further updates from this trial to validate long-term efficacy and safety.
For investors, the data from Eli Lilly's olomorasib trial is significant, potentially altering the competitive landscape of cancer treatments. The combination therapy's high ORR and tolerable safety profile position olomorasib as a strong candidate in the market for KRAS G12C-mutant NSCLC treatments.
Given the current unmet needs in this patient population and the promising early data, olomorasib could capture substantial market share, pending successful Phase 3 results. This potential market disruption could benefit Eli Lilly's stock value in the long-term.
Additionally, the planned continuation into the registrational SUNRAY-01 trial emphasizes Eli Lilly’s strategic commitment to advancing olomorasib. Investors might see this as a commitment to innovation and a promising pipeline, suggesting confidence from the company in this drug's future marketability.
Data demonstrated promising monotherapy activity with olomorasib across a range of KRAS G12C-mutant solid tumors, including non-small cell lung cancer, and a tolerability profile in combination with pembrolizumab that is well-suited to first-line lung cancer development
"Despite recent advances, there remains a significant unmet need for patients with KRAS G12C-mutant cancers," said Timothy Burns, M.D., Ph.D., Associate Professor of Medicine, University of Pittsburgh Medical Center Hillman Cancer Center. "These data show efficacy with olomorasib across tumor types and, importantly, tolerability that suggests it can be combined with immunotherapy, the backbone of first-line treatment for KRAS-mutant NSCLC. In NSCLC, it is also exciting to see promising activity in patients previously treated with a KRAS G12C inhibitor as well as central nervous system (CNS) activity, consistent with the improved potency of this second generation KRAS G12C inhibitor. Collectively, these data point to a promising emerging profile for olomorasib, particularly in NSCLC where new options are needed to improve outcomes for patients."
"As a second generation KRAS G12C inhibitor, olomorasib was specifically designed to offer a differentiated profile that could potentially overcome limitations of currently available treatment options," said David Hyman, M.D., chief medical officer, Lilly. "With these updated data, we are pleased to see our thesis for olomorasib continuing to translate clinically. Through our SUNRAY-01 study, we look forward to further investigating the potential of olomorasib in combination with pembrolizumab-containing regimens in first-line NSCLC, where there remains great need to further impact the disease trajectory for patients with KRAS G12C-mutant lung cancers."
Data from the LOXO-RAS-20001 Phase 1/2 Study
Results presented at ASCO utilized a cutoff date of March 18, 2024. Efficacy results are based on investigator response assessments, and objective response rates (ORR) include responses that are confirmed, as well as those pending confirmation and ongoing.
Olomorasib as Monotherapy in KRAS G12C-Mutant Advanced Solid Tumors
An oral presentation (abstract #3007) detailed updated data for olomorasib monotherapy in patients with KRAS G12C-mutant advanced solid tumors. This dataset consisted of 184 patients, including 42 with NSCLC naïve to a KRAS G12C inhibitor (six with active brain metastases), 41 with NSCLC who had received a prior KRAS G12C inhibitor, 32 with colorectal cancer (CRC), 24 with pancreatic cancer, and 45 with other solid tumors. Patients had received a median of three prior lines of therapy (range 0-11).
Efficacy for olomorasib monotherapy was consistent across a range of solid tumors with an ORR of
Patients were on treatment for a median of 4.7 months and treatment-related adverse events (TRAEs) were predominantly grade 1 with only diarrhea seen in greater than
Olomorasib in Combination with Pembrolizumab in KRAS G12C-Mutant Advanced NSCLC
An oral presentation (abstract #8510) detailed updated data for olomorasib in combination with pembrolizumab in patients with KRAS G12C-mutant advanced NSCLC, studying the two doses (50mg and 100mg BID) under ongoing investigation in first-line NSCLC. This dataset consisted of 64 patients, including patients with first-line metastatic disease and those previously treated (prior KRAS G12C inhibitor, chemotherapy, and/or immunotherapy). Patients received a median of two prior lines of therapy (range: 0-8).
In patients with first-line metastatic NSCLC, across a range of PD-L1 levels, the ORR for olomorasib in combination with pembrolizumab was
The SUNRAY-01 trial (NCT06119581), a global, registrational study investigating olomorasib in combination with pembrolizumab or pembrolizumab plus chemotherapy in first-line NSCLC, is currently enrolling.
KEYTRUDA® is a registered trademark of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc.,
About the LOXO-RAS-20001 Study
LOXO-RAS-20001 is an open-label, multicenter, Phase 1/2 study evaluating the safety, tolerability and preliminary efficacy of olomorasib in patients with KRAS G12C-mutant advanced solid tumors (NCT04956640). The study includes a Phase 1a dose escalation phase of olomorasib monotherapy in KRAS G12C-mutant solid tumors and a Phase 1b dose expansion and optimization phase which are evaluating olomorasib as a monotherapy and in combination with other treatments.
About Olomorasib
Olomorasib (LY3537982) is an investigational, oral, potent, and highly selective second-generation inhibitor of the KRAS G12C protein. KRAS is the most common oncogene across all tumor types, and KRAS G12C mutations occur in
Olomorasib is currently being studied in the LOXO-RAS-20001 Phase 1/2 trial (NCT04956640) in patients with KRAS G12C-mutant NSCLC and other advanced solid tumors and in the pivotal, registrational SUNRAY-01 global study (NCT06119581) investigating olomorasib in combination with pembrolizumab with or without chemotherapy for first-line treatment of KRAS G12C-mutant advanced NSCLC. For additional information about olomorasib clinical trials, please refer to clinicaltrials.gov.
About Lilly
Lilly is a medicine company turning science into healing to make life better for people around the world. We've been pioneering life-changing discoveries for nearly 150 years, and today our medicines help more than 51 million people across the globe. Harnessing the power of biotechnology, chemistry and genetic medicine, our scientists are urgently advancing new discoveries to solve some of the world's most significant health challenges: redefining diabetes care; treating obesity and curtailing its most devastating long-term effects; advancing the fight against Alzheimer's disease; providing solutions to some of the most debilitating immune system disorders; and transforming the most difficult-to-treat cancers into manageable diseases. With each step toward a healthier world, we're motivated by one thing: making life better for millions more people. That includes delivering innovative clinical trials that reflect the diversity of our world and working to ensure our medicines are accessible and affordable. To learn more, visit Lilly.com and Lilly.com/news, or follow us on Facebook, Instagram and LinkedIn. P-LLY
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Cautionary Statement Regarding Forward-Looking Statements
This press release contains forward-looking statements (as that term is defined in the Private Securities Litigation Reform Act of 1995) about olomorasib as a potential treatment for people with certain KRAS G12C-mutant advanced solid tumors and reflects Lilly's current beliefs and expectations. However, as with any pharmaceutical product, there are substantial risks and uncertainties in the process of drug research, development, and commercialization. Among other things, there is no guarantee that planned or ongoing studies will be completed as planned that future study results will be consistent with study results to date, that olomorasib will prove to be a safe and effective treatment for people with certain KRAS G12C-mutant advanced solid tumors, that olomorasib receive regulatory approval, or that Lilly will execute its strategy as expected. For further discussion of these and other risks and uncertainties that could cause actual results to differ from Lilly's expectations, see Lilly's Form 10-K and Form 10-Q filings with the United States Securities and Exchange Commission. Except as required by law, Lilly undertakes no duty to update forward-looking statements to reflect events after the date of this release.
1 Canon J. et al. Nature 2019, 575, 217-223
2 Salem M. et al. Ann Oncol 2021, 32 (3 Suppl): S218
3 Peng S-B, Si C, Zhang Y, et al. Abstract 1259: Preclinical characterization of Ly3537982, a novel, highly selective and potent KRAS-G12C inhibitor. Cancer Research. 2021;81(13_Supplement):1259-1259. doi:10.1158/1538-7445.am2021-1259
Refer to: | Megan Talon; megan.talon@lilly.com; 463-209-1470 (Media) |
Joe Fletcher; jfletcher@lilly.com; 317-296-2884 (Investors) |
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FAQ
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