Adagrasib has shown “clinically meaningful activity” in patients with KRASG12C-mutated solid tumors who had no remaining treatment options, according to an ASCO Plenary Series presentation.

Survival outcomes and response rates were particularly “noteworthy” in pancreatic ductal adenocarcinoma (PDAC) and biliary tract cancer (BTC), said study presenter Shubham Pant, MD, of the University of Texas MD Anderson Cancer Center in Houston.

These results come from KRYSTAL-1, a phase 1/2 trial of patients with KRASG12C-mutated cancers ( Identifier: NCT03785249). The cohort included 64 patients with unresectable or metastatic solid tumors who had no potentially curative treatment options available.

The patients had PDAC (n=21), BTC (n=12), appendiceal cancer (n=10), ovarian cancer (n=5), cancer of unknown primary (n=4), gastroesophageal junction/esophageal cancer (n=4) endometrial cancer (n=3), small bowel cancer (n=3), breast cancer (n=1), and glioblastoma (n=1).

The cohort was a “relatively heavily pretreated population,” Dr Pant said, noting that about a third of patients had received 3 or more prior lines of therapy. The median was 2 prior lines (range, 0-7).

Patents received adagrasib monotherapy orally at 600 mg twice daily. The median follow-up was 16.8 months.

A total of 57 patients had measurable disease at baseline. In this group, the overall response rate (ORR) was 35.1%, and the disease control rate (DCR) was 86%. All 20 responses were partial responses, and 29 patients had stable disease.

The median duration of response was 5.3 months, and the median time to response was 1.4 months. The median progression-free survival (PFS) was 7.4 months, and the median overall survival (OS) was 14.0 months.

Dr Pant highlighted the results in PDAC and BTC in particular. In patients with PDAC, the ORR was 33.3%, the DCR was 81.0%, the median PFS was 5.4 months, and the median OS was 8.0 months.

In patients with BTC, the ORR was 41.7%, the DCR was 91.7%, the median PFS was 8.6 months, and the median OS was 15.1 months.

In the overall cohort, most treatment-related adverse events (TRAEs) were grade 1-2. There was 1 grade 4 TRAE (febrile neutropenia) and no grade 5 TRAEs. TRAEs led to dose reductions in 39.7% of patients and dose interruptions in 44.4%. There were no discontinuations due to TRAEs.

“Adagrasib monotherapy demonstrated clinically meaningful activity in a variety of KRASG12C-mutated solid tumors for which no standard-of-care treatment options are available,” Dr Pant concluded. “The clinical activity of adagrasib in patients with pancreatic cancer and biliary tract cancer is noteworthy, as chemotherapy, as we know, has limited clinical activity in these patient populations in the second-line setting.”

Disclosures: This research was supported by Mirati Therapeutics. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.


Pant S, Yaeger R, Spira AI, et al. KRYSTAL-1: Activity and safety of adagrasib (MRTX849) in patients with advanced solid tumors harboring a KRASG12C mutation. ASCO Plenary Series. April 2023. Abstract 425082.