Daiichi Sankyo initiates phase 2 study of patritumab deruxtecan in advanced colorectal cancer

Daiichi Sankyo Company announced that the first patient has been dosed in a phase 2 study evaluating patritumab deruxtecan (U3-1402), a HER3 directed DXd antibody drug conjugate (ADC), in patients with advanced or metastatic colorectal cancer who are resistant, refractory, or intolerant to at least two prior lines of systemic therapy.

Standard treatment options for patients with advanced or metastatic colorectal cancer include surgery when possible, chemotherapy with or without targeted therapy, and radiation therapy. However, many patients with advanced colorectal cancer will progress through multiple lines of therapy, and prognosis remains poor after failure of these therapies.

It is estimated that up to 83 percent of patients with colorectal cancer overexpress the HER3 protein, which can be associated with an increased incidence of metastases, reduced survival and resistance to standard cancer treatment.

“The prognosis of patients with advanced or metastatic colorectal cancer remains poor, and there is a need to develop new treatment strategies, including targeting HER3,” said Gilles Gallant, BPharm, PhD, FOPQ, Senior Vice President, Global Head, Oncology Development, Oncology R&D, Daiichi Sankyo. “In this study, we are exploring whether the targeted delivery of cytotoxic chemotherapy with patritumab deruxtecan to cancer cells with varying levels of HER3 expression may be a potential treatment option for previously treated advanced or metastatic colorectal cancer.”

The multi-center, open-label, two-cohort, two-part, phase 2 study will evaluate the safety and efficacy of patritumab deruxtecan in patients with advanced or metastatic colorectal cancer who are resistant, refractory, or intolerant to at least two prior approved systemic therapies. Prior treatments must include chemotherapy (fluoropyrimidine, irinotecan and a platinum agent), an anti-EGFR agent if clinically indicated, and an anti-VEGF agent, unless contraindicated. Patients with confirmed microsatellite instability-high (MSI-H) colorectal cancer must have received treatment with an immune checkpoint inhibitor, unless contraindicated.

The first part of the study will include two cohorts of patients with varying levels of HER3 expression. One cohort will include patients with HER3 high expression (IHC 3+ or 2+), and the second cohort will include patients with HER3 low/HER3 negative expression (IHC 1+ or 0). Based on a preliminary review of the data, specifically treatment response in both cohorts, additional patients may be enrolled into a second part of the study, which will further assess treatment with patritumab deruxtecan in patients with either HER3 high expression or both HER3 high and low expression.

The primary objective of the study is to assess the antitumor activity of patritumab deruxtecan, and will evaluate objective response rate (ORR), as assessed by Blinded Independent Central Review per RECIST v1.1, as the primary endpoint. Secondary objectives of the study include the assessment of antitumor activity (evaluated by assessing duration of response (DoR), investigator-assessed ORR, disease control rate (DCR), time to response (TTR), progression-free survival (PFS) and overall survival (OS)), safety and tolerability, level of HER3 protein expression in tumor tissue and its relationship with efficacy, pharmacokinetics and immunogenicity. Secondary efficacy assessments (ORR, DOR, DCR, TTR, and PFS) will be assessed by BICR and investigator per RECIST v1.1.

The study is expected to enroll up to approximately 80 patients in the U.S., Europe and Japan.