Table of contents

• Overview of the Ly3537982 trials
• Conditions being studied
• Trial designs and phases
• Who can participate
• What the trials measure
• Trial-by-trial summary
• Patient-friendly terms

Overview of the Ly3537982 trials

Clinical research on Ly3537982 is focused on cancer patients with a specific genetic change called KRAS G12C.^[1] The studies look at Ly3537982 as a single treatment and also in combination with other anticancer medicines.^[1][2][3]

The trial data show three authorised interventional studies.^{[1][2][3] Two are large Phase 3 studies in non-small cell lung cancer, and one is an earlier Phase 1/2 study in advanced solid tumors.[1][2][3]}

Conditions being studied

One study includes people with KRAS G12C-mutant advanced solid tumors, which means different types of advanced cancers that share the same gene change.^[1] The other two studies focus on KRAS G12C-mutant non-small cell lung cancer.^[2][3]

In the lung cancer studies, one trial includes people with stage IIIB-IIIC or stage IV disease, while another includes people with resected or unresectable disease.^{[2][3] This shows that the research is aimed at both advanced cancer and different treatment settings in lung cancer.[2][3]}

Trial designs and phases

The first study is a Phase 1/2 interventional trial, which is an early research stage that checks safety, dose, and early signs of benefit.^[1] It studies Ly3537982 as monotherapy and in combination with other anticancer therapies.^[1]

The other two studies are Phase 3 trials, which are larger studies that compare treatment groups and measure how well the treatment works in real patient groups.^{[2][3] Both Phase 3 studies compare Ly3537982 combinations against placebo-based treatment plans.[2][3]}

In the first Phase 3 lung cancer study, the trial has a dose optimization part and a safety lead-in part, which means the researchers are first checking the best dose and early safety before comparing results.^[2] In the SUNRAY-02 study, the comparison is Ly3537982 with standard of care medicines versus placebo with the same background treatment.^[3]

Who can participate

People can join these studies only if their cancer has the KRAS G12C mutation.^{[1][2][3] The studies include adults with advanced cancer, and some studies are limited to people with specific lung cancer stages or surgery status.[1][2][3]}

One study includes patients with advanced solid tumors, while the lung cancer studies include stage IIIB-IIIC, stage IV, resected, or unresectable non-small cell lung cancer.^{[1][2][3] This means the trials are not for all cancer patients, but for people with a very specific cancer type and genetic profile.[1][2][3]}

What the trials measure

The Phase 1/2 study measures dose-limiting toxicity, other treatment-related safety problems, and antitumor activity.^[1] Dose-limiting toxicity means side effects that are serious enough to stop dose increases or limit how much treatment can be given.^[1]

That same study also tracks TEAEs, SAEs, deaths, and clinical laboratory abnormalities.^[1] TEAEs are treatment-emergent adverse events, meaning medical problems that appear or get worse after treatment starts, and SAEs are serious adverse events.^[1]

The Phase 3 lung cancer studies focus on cancer control over time, including progression-free survival and disease-free survival.^{[2][3] Progression-free survival means the time before the cancer gets worse, and disease-free survival means the time after treatment when no cancer is found.[2][3]}

One Phase 3 study also uses RECIST v1.1 by BICR for progression-free survival, which means the cancer is measured using standard rules and reviewed by an independent central team.^[2]

Trial-by-trial summary

NCT04956640 is a Phase 1/2 study in people with KRAS G12C-mutant advanced solid tumors.^[1] Its goal is to find the recommended Phase 2 dose, check safety and tolerability, and look for antitumor activity when Ly3537982 is used alone or with other cancer treatments.^[1]

2023-503412-33-00 is a Phase 3 study in stage IIIB-IIIC or stage IV KRAS G12C-mutant non-small cell lung cancer.^[2] It compares Ly3537982 with pembrolizumab against placebo with pembrolizumab, and in another part compares Ly3537982 with pembrolizumab, pemetrexed, and platinum against the same treatment without Ly3537982.^[2]

2024-512302-25-00, also called SUNRAY-02, is a Phase 3 study in resected or unresectable KRAS G12C-mutant non-small cell lung cancer.^[3] It compares Ly3537982 plus pembrolizumab versus placebo plus pembrolizumab in one part, and Ly3537982 plus durvalumab versus placebo plus durvalumab in another part.^[3]

Patient-friendly terms

Interventional study means the researchers give a treatment and then watch what happens.^{[1][2][3] This is different from a study that only observes people without changing treatment.[1][2][3]}

Placebo means a treatment that looks like the study medicine but does not contain the active drug.^{[2][3] It helps researchers compare results fairly.[2][3]}

Standard of care means the usual treatment given for a disease.^[3] In SUNRAY-02, Ly3537982 is studied together with standard treatment medicines, so researchers can see if adding it improves results.^[3]