ASN007

P1/2, N=200, Active, not recruiting, Erasca, Inc. | Phase classification: P1b/2 --> P1/2 | Trial completion date: Nov 2024 --> Nov 2025 | Trial primary completion date: May 2024 --> May 2025

P1/2, N=102, Active, not recruiting, Erasca, Inc. | Recruiting --> Active, not recruiting | Phase classification: P1b/2 --> P1/2 | N=200 --> 102

P1b, N=24, Completed, Erasca, Inc. | Active, not recruiting --> Completed | N=200 --> 24 | Trial completion date: Mar 2024 --> Apr 2023

P1b/2, N=200, Active, not recruiting, Erasca, Inc. | Recruiting --> Active, not recruiting

ERAS-007+EC in pts with BRAF V600E CRC shows acceptable preliminary safety/tolerability and evidence of clinical activity. The highest dose of ERAS-007 evaluated and cleared by the safety review committee to date is 100 mg BID-QW when combined with EC. Observed PK, toxicity, and preliminary activity support continued evaluation of this combination in pts with BRAF V600E CRC.

ERAS-007 in combination with palbo in pts with KRASm/NRASm CRC or KRASm PDAC shows expected preliminary safety with reversible and manageable AEs. The highest dose evaluated and cleared by the safety review committee to date is ERAS-007 100 mg BID-QW in combination with the approved monotherapy dose of palbo 125 mg QD. Clinical trial information: NCT05039177.

P1b, N=200, Active, not recruiting, Erasca, Inc. | Recruiting --> Active, not recruiting | Phase classification: P1b/2 --> P1b

P1b/2, N=0, Withdrawn, Erasca, Inc. | N=120 --> 0 | Recruiting --> Withdrawn

In KRAS mutant CDX and PDX models, this MAPKlamp’s in vitro activity was observed in vivo where it achieved superior tumor growth inhibition and tumor regression relative to ERAS-601 and ERAS-007 monotherapy. This MAPKlamp showed in vitro and in vivo combination activity in KRAS mutant tumors, and these results support its clinical evaluation in RAS/MAPK pathway-driven tumors.

ERAS-007 demonstrated monotherapy activity and combination benefit in cell-based assays as well as superior combination efficacy in vivo relative to respective monotherapy control arms.In summary, ERAS-007 demonstrates promising preclinical activity across a wide range of RAS/MAPK pathway-driven CRC models both as a monotherapy and in combination that support further exploration in the clinic. Accordingly, ERAS-007 combinations with encorafenib + cetuximab in BRAFV600E CRC and with palbociclib in KRASmut CRC are currently being evaluated in the HERKULES-3 phase 1b/2 master protocol (NCT05039177).

In addition, combination treatment with ASN007 and EGFR TKIs significantly decreased the survival of resistant cells, enhanced induction of apoptosis, and effectively inhibited the growth of erlotinib-resistant xenografts, providing the preclinical rationale for testing combinations of ASN007 and EGFR TKIs in EGFR-mutated NSCLC patients. This study emphasizes the importance of targeting ERK signaling in maintaining the long-term benefits of EGFR TKIs by overcoming acquired resistance.

P1b/2, N=200, Recruiting, Erasca, Inc. | Not yet recruiting --> Recruiting

The PI3K inhibitor copanlisib enhances the antiproliferative activity of ASN007 both in vitro and in vivo due to dual inhibition of RAS/MAPK and PI3K survival pathways. Our data provide a rationale for evaluating ASN007 in RAS/RAF-driven tumors as well as a mechanistic basis for combining ASN007 with PI3K inhibitors.

P1, N=49, Completed, Asana BioSciences | Active, not recruiting --> Completed