S95027 / Servier - LARVOL DELTA

[VIRTUAL] Safety and preliminary clinical activity of the MET antibody mixture, Sym015 in advanced non-small cell lung cancer (NSCLC) patients with MET amplification/exon 14 deletion (METAmp/Ex14∆). (ASCO 2020) - P1a | "Sym015 was well-tolerated at the RP2D with a response rate similar to MET TKI in MET-treatment naïve METAmp/Ex14Δ NSCLC and seems to delay disease progression in MET TKI pretreated NSCLC pts. Combination with MET TKI to delay or prevent resistance should be further explored. Research Funding: Symphogen A/S"

Clinical • Fatigue • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Thoracic Cancer

A phase Ia/IIa trial of Sym015, a MET antibody mixture, in patients with advanced solid tumours (ESMO 2019) - P1a; "Sym015 was well tolerated with early evidence of antitumor activity. Predictive biomarker analysis is underway. The study continues to enroll NSCLC patients with MET Amp and/or MET Ex14Δ ."

Clinical • P1/2 data

Sym015 (Anti-MET) in Patients With Advanced Solid Tumor Malignancies (clinicaltrials.gov) - P1a; N=57; Completed; Sponsor: Symphogen A/S; Active, not recruiting ➔ Completed

Clinical • Trial completion • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR • KRAS • MET

Anti-tumor effects of Sym015 in HGF overexpressing gastric cancer cell lines (AACR 2018) - "Consequently, Sym015 was effective in HGF overexpressing cell lines and HGF overexpression induced Sym015 sensitivity was shown in IM95m and the inhibitory effect of invasiveness was shown in SNU484. We suggest that HGF overexpression influences the sensitivity of MET inhibitor and could be a potential predictive marker in GC."

Preclinical • Gastric Cancer

ASCO 2020 Annual Meeting Conference Report - "'The two monoclonal antibodies of Sym015 bind to non-overlapping epitopes on MET,' explained Ross Camidge, MD...'The particular importance of this approach is that it’s an additional way of downregulating MET signaling separate from that of tyrosine kinase inhibitors and may well work when kinase inhibitors fail because of kinase domain mutations.'"

Media quote

MET antibody mixture Sym015 is safe and demonstrates clinical activity in NSCLC - P2, N=45; Basket (NCT02648724); Sponsor: Symphogen A/S; "'The two monoclonal antibodies of Sym015 bind to non-overlapping epitopes on MET', explained Ross Camidge...'The particular importance of this approach is that it’s an additional way of downregulating MET signaling separate from that of tyrosine kinase inhibitors and may well work when kinase inhibitors fail because of kinase domain mutations.'"

Media quote • P2 data

Sym015 shows superior specificity compared to TKIs for NSCLC (ecancer) - "Dr Ross Camdige speaks to ecancer online about his ASCO 2020 virtual presentation which discussed Sym015 for NSCLC....Combination with MET TKI to delay or prevent resistance should be further explored."

Video

Symphogen A/S advances Sym015 into clinical development using Selexis SGEs (Selexis Genetic Elements) (Businesswire) - "Selexis SA...announced today that Symphogen A/S...has progressed its Sym015 clinical candidate into a Phase 1 dose escalation trial in patients with solid tumors. Symphogen relied upon Selexis SGE (Selexis Genetic Elements) to facilitate the rapid, stable, and cost-effective expression of Sym015...."

New P1 trial • Oncology

Sym015 (MET) (IASLC-LCTT 2020) - No abstract available

Sym015 (Anti-MET) in Patients With Advanced Solid Tumor Malignancies (clinicaltrials.gov) - P1a; N=72; Active, not recruiting; Sponsor: Symphogen A/S; Recruiting ➔ Active, not recruiting; Trial primary completion date: Dec 2019 ➔ Oct 2020

Clinical • Enrollment closed • Trial primary completion date • EGFR • KRAS

Acquired resistance to a MET antibody in vivo can be overcome by the MET antibody mixture Sym015. (PubMed, Mol Cancer Ther) - "This study investigated mechanisms underlying in vivo resistance to two antibody therapeutics currently in clinical development: an analogue of the MET-targeting antibody emibetuzumab and Sym015, a mixture of two antibodies targeting nonoverlapping epitopes of MET. Importantly, both resistant models were sensitive to treatment with Sym015 in vivo due to antibody-dependent cellular cytotoxicity-mediated tumor growth inhibition, MET degradation, and signaling inhibition. Taken together, our data provide key insights into potential mechanisms of resistance to a single MET-targeting antibody, demonstrate superiority of Sym015 in preventing acquired resistance, and confirm Sym015 anti-tumor activity in tumors resistant to a single MET antibody."

Journal • Preclinical

Sym015 (Anti-MET) in Patients With Advanced Solid Tumor Malignancies (clinicaltrials.gov) - P1a; N=72; Recruiting; Sponsor: Symphogen A/S; Trial completion date: Sep 2019 ➔ Sep 2020; Trial primary completion date: Mar 2019 ➔ Dec 2019

Clinical • Trial completion date • Trial primary completion date