tarextumab (OMP-59R5) / Mereo Biopharma, Novartis - LARVOL DELTA

Results of a randomized, placebo-controlled, phase 2 study of tarextumab (TRXT, anti-Notch2/3) in combination with etoposide and platinum (EP) in patients (pts) with untreated extensive-stage small-cell lung cancer (ED-SCLC) (ESMO 2017) - P1b/2; "Pts were randomized 1:1 to platinum (cisplatin 75 mg/m2 or carboplatin AUC of 5 mg/ml*min on day 1, investigator’s choice) + etoposide (EP) 100 mg/m2 on days 1-3 + TRXT 15 mg/kg on day 1 or EP + placebo (pbo) every 21 days. Tarextumab in combination with platinum-based therapy did not improve PFS, OS, ORR in previously untreated SCLC. Biomarker analysis failed to establish a predictive marker for TRXT efficacy. Pts treated with TRXT experienced more toxicity."

Combination therapy • P2 data • Small Cell Lung Cancer

Results of a randomized phase II trial of an anti-notch 2/3, tarextumab (OMP-59R5, TRXT, anti-Notch2/3), in combination with nab-paclitaxel and gemcitabine (Nab-P+Gem) in patients (pts) with untreated metastatic pancreatic cancer (mPC). (ASCO-GI 2017) - P1b/2; "Addition of TRXT to Nab-P+Gem did not improve OS in 1st line mPC. A potential detrimental effect on PFS and ORR was seen in subjects with N3 < 25%ile.nBackground: Tarextumab (TRXT), fully human IgG2 antibody inhibits signaling of Notch2/ 3 receptors."

Clinical • P2 data • Biliary Cancer • Biosimilar • Gastrointestinal Cancer • Oncology • Pancreatic Cancer

Circulating Tumor Cells (CTCs) in patients with extensive stage small cell lung cancer and their association with clinical outcome (AACR 2017) - P1b/2; "...Tarextumab (TRXT, anti-Notch2/3, OMP-59R5) is a fully human monoclonal antibody that targets the Notch2 and Notch3 receptors. PINNACLE is a Phase 1b/2 trial of TRXT in combination with etoposide and platinum therapy (EP) in patients with untreated extensive stage small cell lung cancer (ES-SCLC)... Our findings suggest that CTCs are frequently detectable in patients and are a prognostic factor in ES-SCLC. CTCs decrease with TRXT and platinum-based chemotherapy. Updated results will be presented."

Biomarker • Clinical • Biosimilar • Lung Cancer • Oncology • Small Cell Lung Cancer

A Review on the Efficacy and Safety of Nab-Paclitaxel with Gemcitabine in Combination with Other Therapeutic Agents as New Treatment Strategies in Pancreatic Cancer. (PubMed, Life (Basel)) - "The seven therapeutic agents were ibrutinib, necuparanib, tarextumab, apatorsen, cisplatin, enzalutamide, and momelotinib. The triple regimen is emerging as the first-line option for patients with pancreatic cancer, albeit with some limitations. Thus, further studies of this regimen are recommended."

Combination therapy • Journal • Review • Gastrointestinal Cancer • Hepatology • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor

A randomized phase II trial of nab-paclitaxel and gemcitabine with tarextumab or placebo in patients with untreated metastatic pancreatic cancer. (PubMed, Cancer Med) - P1b/2 | "The addition of tarextumab to nab-paclitaxel and gemcitabine did not improve OS, PFS, or ORR in first-line metastatic PDAC, and PFS was specifically statistically worse in the tarextumab-treated patients."

Biomarker • Clinical • Journal • P2 data • Gastrointestinal Cancer • Hematological Disorders • Hepatology • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Thrombocytopenia

OncoMed achieves $72.5 million in milestone payments from Celgene; Announces year-end cash balance (GlobeNewswire) - "OncoMed achieved the $70 million safety milestone from Celgene based on an analysis of available Phase 1b and blinded interim Phase 2 clinical trial safety data associated with the demcizumab..."; Anticipated survival data of P1b pancreatic cancer study of demcizumab and Abraxane combination in ASCO GI 2016; Anticipated intiation of P1b of demcizumab in combination with pembrolizumab in Q1 2016; Anticpated enrollment Completion of P2 YOSEMITE trial; Anticipated results from P1b ovarian cancer trial of demcizumab plus paclitaxel; Anticipated P1b data of tarextumab plus chemotherapy in SCLC at 16th IASLC conference; Anticipated top-line results from the Phase 2 'ALPINE' trial; Anticipated initiation of P1b trial of Brontictuzumab in colorectal cancer; Anticipated initiation of P1a data of OMP-305B83."

Anticipated conference • Anticipated enrollment status • Anticipated new P1 trial • Anticipated P1 data • Anticipated P2 data • Commercial • Gastrointestinal Cancer • Hematological Malignancies • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Pancreatic Cancer • Small Cell Lung Cancer

EGFR/Notch Antagonists Enhance the Response to Inhibitors of the PI3K-Akt Pathway by Decreasing Tumour-Initiating Cell Frequency. (PubMed, Clin Cancer Res) - "These findings suggest that the co-blockade of EGFR and Notch signalling has the potential to increase the response to PI3K inhibition and PTG12 may gain clinical efficacy when combined with PI3K blockage in cancer treatment."

Journal • Oncology • Transplantation • Triple Negative Breast Cancer

OncoMed's phase 2 trial of tarextumab in small cell lung cancer does not meet endpoints (OncoMed Press Release) - P2, N=145; NCT01859741; "OncoMed Pharmaceuticals...today reported top-line results from...PINNACLE clinical trial of tarextumab...in previously untreated patients with extensive-stage small cell lung cancer...the trial did not meet its primary endpoint of progression-free survival or secondary endpoints of overall survival and biomarkers reflective of Notch pathway gene activation...it will discontinue enrollment in the Phase 1b clinical trial of brontictuzumab...in combination with trifluridine/tipiracil (Lonsurf®) in third-line colorectal cancer patients."

Enrollment closed • P2 data • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Small Cell Lung Cancer

MorphoSys: Leerink Partners Annual Emerging Biotech Conference (Morphosys) - Anticipated data from P2 ALPINE trial (NCT01647828) for pancreatic cancer in 2016

Anticipated P2 data • Oncology • Pancreatic Cancer

OncoMed announces abstracts accepted for presentation at the 2015 ASCO Annual Meeting (OncoMed Press Release) - "OncoMed will present new clinical data from clinical trials of its lead anti-cancer stem cell therapeutics, demcizumab and tarextumab. Final data from OncoMed's Phase 1b clinical trial of tarextumab (anti-Notch2/3, OMP-59R5) in small cell lung cancer...[and] New data from the company's Phase 1b clinical trials of demcizumab (OMP-21M18, anti-DLL4) in pancreatic cancer and non-small cell lung cancer (NSCLC) will be presented in posters during the meeting."

Anticipated conference • Anticipated P1 data • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer

Morphosys: J.P. Morgan Healthcare Conference (Morphosys) - Anticipated data from P2 trial in pancreatic cancer in 2016

Anticipated P2 data • Oncology • Pancreatic Cancer

"$OMED phase 2 PINNACLE SCLC trial completed enrollment. Data by EOY or early 2017." - @bradloncar

Anticipated P2 data • Enrollment closed • Oncology • Small Cell Lung Cancer

A Dose Escalation Study of OMP-59R5 in Subjects With Solid Tumors (clinicaltrials.gov) - P1; N=42; Completed; Sponsor: OncoMed Pharmaceuticals, Inc.; Active, not recruiting ➔ Completed

Trial completion • Biosimilar • Oncology

A Phase 1b/2 study of OMP-59R5 in combination with gemcitabine in subjects with previously untreated stage iv pancreatic cancer (ALPINE) (clinicaltrials.gov) - P1/2, N=154; Sponsor: OncoMed Pharmaceuticals; Not yet recruiting -> Recruiting

Enrollment open • Pancreatic Cancer

A phase 1b/2 study of OMP-59R5 in combination with etoposide and cisplatin in subjects with untreated extensive stage small cell lung cancer (PINNACLE) (clinicaltrials.gov) - P1/2, N=80; Sponsor: OncoMed; Recruiting; New P1/2 trial.

New P1/2 trial • Oncology

OncoMed: ASCO 2015 (OncoMed) - "TRXT in combination with EP was well tolerated up to 15 mg/kg Q3W. One DLT of Grade 3 nausea was observed in one pt (10 mg/kg Q3W)"; "Diarrhea, fatigue, nausea, decreased appetite and vomiting were the most common TRXT associated AEs (mostly Grade 1 or 2 events, and manageable with supportive care)"; "RECIST response (unconfirmed) to EP + TRXT(all dose cohorts) was 77%; greater tumor reduction at high dose TRXT (≥12.5mg/kg Q3W)"; "The median PFS and OS values were 4.4 mos and 8.2 mos for all 27 pts, respectively"; "There was a potential trend of longer survival in higher dose (TRXT≥ 12.5 mg/kg) cohorts, particularly in subjects with tumors with high Notch3 tumor levels. More follow-up is needed and this will be verified in the Ph2 randomized portion of the trial"

P1 data • Oncology • Small Cell Lung Cancer

OncoMed: 2017 Outlook (OncoMed) - Anticipated data presentation from P2 PINNACLE trial (NCT01859741) for small cell lung cancer at a medical meeting in H2 2017

Anticipated P2 data • Oncology • Small Cell Lung Cancer

Oncomed: Biocentury's NewsMakers In The Biotech Industry Conference (OncoMed) - "Anti-Notch2/3 (OMR-59R5) summary"; "Potential GSK Opt-In Program"; "Ph1a study completed: Oral Plenary Presentation: Mol Targets and Cancer Therapeutics 2012"; "Safety: Well tolerated in refractory solid tumor patients"; "Toxicity: On-target diarrhea"; "Maximum tolerated dose (MTD) established for 3 dosing schedules (QW, Q2W,Q3W)"; "Efficacy: Prolonged stable disease"; "Triple Negative BC (JAG1 amplification), Liposarcoma, Adeniod Cystic Carcinoma, Rectal Cancer, Kaposi Sarcoma"

P1 data • Oncology • Pancreatic Cancer

OncoMed: Q1 2014 Results (OncoMed) - Anticipated presentation of interim data from P1b PINNACLE trial in combination with etoposide and cisplatin for extensive-stage small cell lung cancer at ASCO (May 30-June 3, 2014); Anticipated initiation of P2 portion of P1/2 ALPINE trial for pancreatic cancer in 2014; Anticipated initiation of P2 portion of P1/2 PINNACLE trial for small cell lung cancer in 2014

Anticipated new P1/2 trial • Anticipated P1/2 data • Oncology • Pancreatic Cancer

OncoMed: Leerink Immuno-Oncology Roundtable Conference (OncoMed) - "Tarextumab Phase 1B PINNACLE: Biomarker and Survival Analysis"; "Dose response and biomarker trends observed"; "Potentially longer survival noted in patients who received higher doses of tarextumab + platinum therapy and among Notch3 high patients"

P1 data • Oncology

A first-in-human phase I study to evaluate the fully human monoclonal antibody OMP-59R5 (anti-Notch2/3) administered intravenously to patients with advanced solid tumors (ASCO 2012) - Presentation time: Sat, Jun 2, 1:15 PM - 5:15 PM; Anticipated presentation at ASCO 2012

Anticipated P1 data presentation • Oncology

A first-in-human phase I study to evaluate the fully human monoclonal antibody OMP-59R5 (anti-Notch2/3) administered intravenously to patients with advanced solid tumors (ASCO 2012) - Presentation time: Saturday June 2, 1:15 PM to 5:15 PM; P1, N=24; PK of OMP-59R5 was characterized by fast and dose-dependent clearance; Two patients (Kaposi’s sarcoma at 5mg/kg and adenoid cystic carcinoma at 2.5mg/kg) had prolonged stable disease for ≥110 days; PD analyses for Notch pathway modulation are ongoing

P1 pharmacokinetic data • Oncology

Phase 1b of anticancer stem cell antibody OMP-59R5 (anti-Notch2/3) in combination with etoposide and cisplatin (EP) in patients (pts) with untreated extensive-stage small-cell lung cancer (ED-SCLC) (ASCO 2014) - Presentation time: Saturday, May 31; 1:15 PM - 5:00 PM; Abstract #7601; P1, N=8; NCT01859741; Sponsor: Oncomed; "No DLTs have occurred. Frequently reported (>25%) adverse events (all grades, G) regardless of relationship were: fatigue(62.5%), nausea(62.5%), anemia(50%), diarrhea(50%), peripheral edema(50%), alopecia(37.5%), blood creatinine increase(37.5%), decreased appetite(37.5%), neutropenia(37.5%), and weight loss(37.5%)..."

Adverse events • P1 data • Non Small Cell Lung Cancer • Oncology

Phase 1b trial of anti-notch 2/3 antibody OMP-59R5 in combination with etoposide and cisplatin (EP) in patients (pts) with untreated extensive-stage small-cell lung cancer (ED-SCLC): The PINNACLE study (ESMO 2014) - Presentation time: 29.09.2014, 12:45 - 13:45, Abstract #1473P; P1, N=11; "OMP-59R5 with EP is well tolerated. The MTD has not been reached. Encouraging anti-tumor activity is observed."

P1 data • Oncology

Biomarker analysis in Phase 1b study of anti-cancer stem cell antibody tarextumab (TAR) in combination with nab-paclitaxel and gemcitabine (Nab-P+Gem) demonstrates pharmacodynamic (PD) modulation of the Notch pathway in patients (pts) with untreated metas (EORTC-NCI-AACR 2014) - Abstract #465; P1b, N=40; "Notch pathway-related genes including HEYL, HES2, and NOTCH2 and cancer stem cell markers were found to be regulated in hair follicles at TAR doses of 7.5 mg/kg and above in combination with Nab-P+Gem. Plasma and blood RNA biomarkers were also modulated by TAR plus Nab-P+Gem."

Biomarker • P1 data • Oncology • Pancreatic Cancer