olomorasib (LY3537982)

P1, N=12, Active, not recruiting, Eli Lilly and Company | Recruiting --> Active, not recruiting

P1/2, N=550, Recruiting, Eli Lilly and Company | Trial completion date: Feb 2026 --> Jun 2026 | Trial primary completion date: Feb 2026 --> Jun 2026

P1, N=35, Completed, Eli Lilly and Company | Not yet recruiting --> Completed | N=56 --> 35

P3, N=936, Not yet recruiting, Jilin Cancer Hospital; Jilin Cancer Hospital

P1, N=12, Recruiting, Eli Lilly and Company | Trial completion date: Apr 2027 --> Jan 2026 | Trial primary completion date: Apr 2026 --> Jan 2025

P1/2, N=550, Recruiting, Eli Lilly and Company | Trial completion date: Sep 2025 --> Feb 2026 | Trial primary completion date: Sep 2025 --> Feb 2026

Olomorasib demonstrates efficacy across a range of KRAS G12C-mutant solid tumors with a favorable safety profile including in pts with prior G12Ci intolerance. Activity of the second-generation G12Ci olomorasib after prior exposure to G12Ci demonstrates the increased potency and target coverage these agents can deliver compared to first generation inhibitors. Phase 2 expansion is currently enrolling pts with PANC, and a global registrational study investigating olomorasib in combination with pembrolizumab in first-line NSCLC is ongoing (NCT06119581).

P1, N=12, Recruiting, Eli Lilly and Company | Not yet recruiting --> Recruiting

P1, N=12, Not yet recruiting, Eli Lilly and Company

P3, N=1016, Recruiting, Eli Lilly and Company | Not yet recruiting --> Recruiting

P1, N=30, Completed, Eli Lilly and Company | Recruiting --> Completed

P1/2, N=450, Recruiting, Eli Lilly and Company | Phase classification: P1a/1b --> P1/2

In pts with GI tumors, LY3537982 alone or in combination with cetuximab demonstrated preliminary efficacy and a favorable safety profile. Clinical trial information: NCT04956640. >aEfficacy evaluable pts are those who had at least 1 post-baseline response assessment or had discontinued treatment before the first post-baseline assessment.bDCR = PR+SD.c1 CRC, 2 PANC, and 1 duodenal cancer pt (other GI) have unconfirmed PR, ongoing and pending confirmation.dOther GI includes duodenal cancer (n=3), small intestine (n=2), esophageal cancer, jejunal adenocarcinoma (both n=1).e1 pt with small intestine cancer is not yet evaluable.f8 pts are not yet evaluable.g3 pts have unconfirmed PR, ongoing and pending confirmation.

P3, N=1016, Not yet recruiting, Eli Lilly and Company

P1, N=56, Not yet recruiting, Eli Lilly and Company

LY3537982 demonstrated a favorable safety profile, including the absence of high-grade liver toxicity, and tolerance in pts previously intolerant to other KRAS G12C inhibitors. Preliminary efficacy was observed with LY3537982 monotherapy across multiple tumor types. Updated data in more than 100 pts, including data in combination with pembrolizumab and cetuximab will be presented.Table: Preliminary LY3537982 Monotherapy EfficacyNSCLC (KRAS G12Ci naïve)(N=5)NSCLC(Prior KRAS G12Ci treated) (N=11)CRCd(N=17)PANCd(N=8)Other tumor typesd,f(N=15)Efficacy Evaluablea, n5915811ORR, n (%)3 (60%)01 (7%)3 (38%)4 (36%)BOR, n (%)PR, n (%)3 (60%)c01 (7%)e3 (38%)e4 (36%)gSD, n (%)1 (20%)6 (67%)13 (87%)4 (50%)6 (55%)PD, n (%)1 (20%)3 (33%)1 (7%)1 (13%)1 (9%)DCRb, n (%)4 (80%)6 (67%)14 (93%)7 (88%)10 (91%)Abbreviations: CRC, colorectal cancer; NSCLC, non-small cell lung cancer; PANC, pancreatic cancera Efficacy evaluable pts are those who had at least one post-baseline response assessment or had discontinued treatmentb DCR includes PR+SDc 3 NSCLC pts have unconfirmed PRs, ongoing and pending confirmation as of the data cut-off dated All pts KRAS G12C inhibitor naïve, prior KRAS G12C inhibitor therapy not permitted for tumor types other than NSCLCe 1 CRC pt and 1 PANC pt have unconfirmed PR, ongoing and pending confirmation as of the data cut-off datef Other tumor types include cholangiocarcinoma (n=4), chondrosarcoma (n=1), jejunal adenocarcinoma (n=1), large cell neuroendocrine of lung (n=1), nasal malignant melanoma (n=1), ovarian cancer (n=3), salivary adenoid cystic carcinoma (n=1), small intestine cancer (n=1), tracheal basaloid squamous cell carcinoma (n=1), and upper tract urothelial carcinoma (n=1)g PRs observed in pts with tracheal basaloid squamous cell carcinoma, cholangiocarcinoma, nasal malignant melanoma, and ovarian cancer (1 each)

P1a/1b, N=400, Recruiting, Eli Lilly and Company | Trial completion date: Nov 2023 --> Sep 2025 | Trial primary completion date: Nov 2023 --> Sep 2025

Key objectives of Phase 1b are to determine the safety and tolerability of LY3537982 monotherapy, and in combination with various agents: abemaciclib, erlotinib, cetuximab, an investigational ERK inhibitor (LY3214996), an investigational Aurora A kinase inhibitor (LY3295668), and an anti-PD1 antibody. Key exclusion criteria include presence of serious cardiac conditions, interstitial lung disease, symptomatic CNS malignancy, symptomatic CNS metastasis, or carcinomatous meningitis. The trial is currently enrolling patients (NCT04956640).

P1a/1b, N=260, Recruiting, Eli Lilly and Company | Not yet recruiting --> Recruiting

P1a/1b, N=260, Not yet recruiting, Eli Lilly and Company

LY3537982 inhibited KRAS-GTP loading with an IC50 value of 3.35 nM in the KRAS-G12C mutant H358 lung cancer cell line, while AMG510 and MRTX849 had IC50 values of 47.9 nM and 89.9 nM, respectively...Mechanism-based combinational screens have also identified certain targeted therapies that can synergize with LY3537982 to achieve better anti-tumor activity in vitro and in vivo, including abemaciclib, the selective AurA inhibitor LY3295668, and cetuximab. Together these data suggest that in certain biologic contexts, broader and more durable anti-tumor activity could be achieved with combination regimens. A first-in-human Phase 1 clinical trial is planned for 2021.