Phase II DESTINY-CRC01 trial of Enhertu/Enhurtu demonstrated meaningful activity in patients with HER2 positive unresectable and/or metastatic colorectal cancer.- Daiichi Sankyo + AstraZeneca

Results from the phase II DESTINY-CRC01 trial of Daiichi Sankyo Company, Limited and AstraZeneca’s Enhurtu (fam-trastuzumab deruxtecan-nxki) demonstrated clinically meaningful activity in patients with HER2 positive unresectable and/or metastatic colorectal cancer who received at least two prior lines of standard treatment. These results were presented at the 2020 American Society of Clinical Oncology Virtual Scientific
Program (#ASCO20). Colorectal cancer is the third most common cancer and second most common cause of cancer death worldwide. There are currently no medicines approved to specifically treat HER2 positive colorectal cancer, which affects approximately two to five percent of patients with colorectal cancer.

The primary endpoint of confirmed objective response rate (ORR), also called a tumor response rate, which was assessed by independent central review, showed 45.3% of patients with HER2 positive advanced colorectal cancer (defined as IHC 3+ or IHC 2+/ISH+) treated with Enhurtu monotherapy (6.4mg/kg) achieved a tumor response. A disease control rate (DCR) of 83.0% was observed with a median progression free survival (PFS) of 6.9 months. Median duration of response (DoR) and overall survival (OS) have not yet been reached at the time of data cut-off. The overall safety and tolerability profile of Enhurtu in DESTINY-CRC01 was consistent with that seen in previously reported ENHERTU trials.

The most common grade 3 or higher treatment-emergent adverse events were decreased neutrophil count (25.6%) and anemia (14.1%). There were five cases (6.4%) of treatment related interstitial lung disease (ILD) and pneumonitis determined by an independent adjudication committee. Two were grade 2 and one was grade 3. Two deaths (grade 5) were determined to be due to ILD.

Prespecified exploratory analysis evaluated ORR in subgroups, including patients previously treated with a prior anti-HER2 regimen (n=16). In these patients an ORR of 43.8% was seen. Patients were treated with a median of four prior lines of therapy (range, 2-11) with all patients having received prior chemotherapy treatment with irinotecan and oxaliplatin. The median treatment duration was 4.8 months (range, 1-11). As of data cut-off on August 9, 2019, 38.5% (30 out of 78) remained on treatment across all cohorts.

Comment: The ongoing Phase II DESTINY-Gastric02 study will be used to support planned filings in the US and Europe.