Dataset Information

A phase I study of LY3164530, a bispecific antibody targeting MET and EGFR, in patients with advanced or metastatic cancer.

ABSTRACT:

Purpose

The phase I study characterized the safety, pharmacokinetics, anti-tumor activity, and recommended phase II dose/schedule of LY3164530 in patients with advanced or metastatic cancer.

Methods

Patients received LY3164530 on days 1 and 15 (Schedule 1: 300, 600, 1000, and 1250 mg) or Days 1, 8, 15, and 22 (Schedule 2: 500 and 600 mg) of each 28 days cycle. Dose escalation used a modified toxicity probability interval model.

Results

Dose escalation defined a maximum tolerated dose (MTD) of 1000 mg on Schedule 1 and 500 mg on Schedule 2. Treatment-emergent adverse events related to study treatment were consistent with epidermal growth factor receptor (EGFR) inhibition and included maculopapular rash/dermatitis acneiform (83%, Grade 3/4 17%), hypomagnesemia (55%, Grade 3/4 7%), paronychia (35%), fatigue (28%, Grade 3/4 3%), skin fissures (24%), and hypokalemia (21%, Grade 3/4 7%). Partial response was achieved in three patients on Schedule 2 with colorectal cancer (n?=?2) or squamous cell cancer. Overall response rate (ORR) was 10.3%, disease control rate (ORR?+?stable disease [SD]) was 51.7 and 17.2% of patients had SD???4 months. The in vivo stability of the bispecific antibody was confirmed. Schedule 2 provided greater and more consistent inhibition of mesenchymal-epithelial transition (MET)/EGFR throughout the dosing interval than Schedule 1.

Conclusions

Although this study defined the LY3164530 MTD and pharmacokinetics on both schedules, significant toxicities associated with EGFR inhibition and lack of a potential predictive biomarker limit future development. Nonetheless, the results provide insight into the development of bispecific antibody therapy.

SUBMITTER: Patnaik A

PROVIDER: S-EPMC6105165 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature

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Publications

A phase I study of LY3164530, a bispecific antibody targeting MET and EGFR, in patients with advanced or metastatic cancer.

Patnaik Amita A Gordon Michael M Tsai Frank F Papadopoulos Kyriakos P KP Rasco Drew D Beeram Muralidhar M Fu Siqing S Janku Filip F Hynes Scott M SM Gundala Sushma R SR Willard Melinda D MD Zhang Wei W Lin Aimee Bence AB Hong David D

Cancer chemotherapy and pharmacology 20180620 3

<h4>Purpose</h4>The phase I study characterized the safety, pharmacokinetics, anti-tumor activity, and recommended phase II dose/schedule of LY3164530 in patients with advanced or metastatic cancer.<h4>Methods</h4>Patients received LY3164530 on days 1 and 15 (Schedule 1: 300, 600, 1000, and 1250 mg) or Days 1, 8, 15, and 22 (Schedule 2: 500 and 600 mg) of each 28 days cycle. Dose escalation used a modified toxicity probability interval model.<h4>Results</h4>Dose escalation defined a maximum tole ...[more]

PMID: 29926131

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Dataset Information

A phase I study of LY3164530, a bispecific antibody targeting MET and EGFR, in patients with advanced or metastatic cancer.

Purpose

Methods

Results

Conclusions

Publications

A phase I study of LY3164530, a bispecific antibody targeting MET and EGFR, in patients with advanced or metastatic cancer.

Similar Datasets

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