Precision medicines, purpose-built to illuminate the path forward
We envision a future in which each patient’s unique genomic testing result can be matched with a targeted treatment journey.
What do we do?
At Elevation Oncology, we focus on the identification and targeted inhibition of each tumor’s specific driver alterations. We believe that this is the most direct path to delivering improved care and outcomes to our patients.
While each driver alteration may individually be rare, our combined efforts as part of a vibrant precision medicine community enable the development of a personalized treatment plan for each individual cancer patient.
Our first clinical trial, CRESTONE (pronounced CRESS-tone), is a Phase 2 study of seribantumab in cancer patients with a solid tumor of any origin that expresses a genomic change called an NRG1 fusion. The CRESTONE study is actively enrolling patients now.
What is seribantumab?
Seribantumab is a fully human monoclonal antibody designed to stop the HER3 signaling that sustains an NRG1 fusion-positive tumor. Seribantumab binds to HER3 so that the NRG1 fusion protein that over-activates it cannot. We believe that seribantumab may offer a precise treatment path forward for patients whose tumor’s growth is driven by an NRG1 fusion.
Seribantumab was originally developed and tested by Merrimack Pharmaceuticals and has the benefit of experience in more than 800 patients. Throughout multiple clinical studies, seribantumab has demonstrated a consistent and well-tolerated safety profile both when administered alone and in combination with other cancer treatments. [1, 2] This prior testing provides our clinical investigators with important experience to confidently treat their patients with seribantumab.
Our job at Elevation Oncology is to confirm the specific patient population that can best benefit from seribantumab, and make sure that the drug is accessible for those patients. Our Phase 2 study, CRESTONE, is now open and enrolling in the US.
What do I need to know about NRG1 fusions?
NRG1 fusions are rare genetic alterations resulting from the accidental fusion of the NRG1 gene with a second gene. These alterations can happen in cells anywhere in your body and can cause unregulated growth and proliferation leading to the formation of a tumor. [3, 4] Because of this, NRG1 fusions are considered to be “oncogenic driver” alterations. [5, 6]
While there are multiple known oncogenic driver alterations, we now know that tumors carrying an NRG1 fusion are unlikely to have any of the other known oncogenic drivers.[3, 4, 6, 7] This suggests that when NRG1 fusions are found in a tumor, they are very likely to be the unique driving cause of that tumor’s growth and survival.
Cutting-edge diagnostics now have the ability to identify NRG1 fusions with high sensitivity. In parallel, emerging scientific evidence is illuminating the critical need to inhibit the HER3 pathway in tumors that carry an NRG1 fusion. [4, 6, 7, 8] These advancements form a strong scientific rationale to test therapeutics that blocks HER3, like seribantumab, in patients whose tumors test positive for an NRG1 fusion.
What is HER3 and how does it relate to NRG1 fusions?
HER3 (or ERBB3) refers to a receptor found commonly on the surfaces of cells throughout the body. The normal NRG1 protein can be thought of as the “key” to HER3 and binds to the receptor to activate it. Activating HER3 sets off a chain reaction that signals the cell to grow and proliferate.
In a healthy cell, the amount of NRG1 protein available is usually tightly regulated by the cell to control its growth. However, in cancer cells where there is abnormal growth and proliferation, there is often a problem with the regulation of the HER3 pathway that causes it to become over-active. 
NRG1 fusions have recently been identified as a rare cause of HER3 over-activation. Like normal NRG1 proteins, NRG1 fusion proteins often retain the ability to activate HER3, but their un-regulated production leads to HER3 over-activation and tumorigenesis. Critically, tumors with NRG1 fusions are unlikely to carry any other genomic alterations that are known to drive tumor growth. [3, 4, 6, 7] When NRG1 fusions are found, their over-activation of HER3 is likely to be the primary driver of tumor survival.
How does seribantumab affect tumors that have an NRG1 fusion?
HER3 inhibitors like seribantumab have been shown in previous clinical trials to stop over-activation of the HER3 pathway and have been widely studied as a potential cancer treatment.
Today we know that cancer cells often use multiple different pathways together to sustain their survival. While HER3 over-activation is commonly found, it may not always be the primary driver of a tumor’s growth and proliferation. Clinically, we have seen that when HER3 over-activation has not been confirmed to be the unique driver of a tumor’s survival, investigational treatment with HER3 inhibiting drugs such as seribantumab results in limited efficacy. [1, 2] To improve patient outcomes, it is critical to identify tumors where HER3 is likely to be the primary oncogenic driver.
NRG1 fusions have recently been identified as a unique oncogenic driver leading to HER3 over-activation. [3, 4, 6, 7] In in tumors with an NRG1 fusion, inhibiting the HER3 signaling pathway with a therapeutic like seribantumab should stop the primary cause of the tumor’s growth.  Seribantumab binds to HER3 so that the NRG1 fusion protein cannot, preventing activation of the HER3 signaling that sustains the tumor. We believe that seribantumab may offer a precise treatment path forward for patients whose tumor’s growth is driven by an NRG1 fusion.
What kinds of cancer may seribantumab treat?
NRG1 fusions have the potential to occur in cells anywhere in the body and have been identified in at least ten different tumor types to date. While they have primarily been found in specific kinds of lung and pancreatic cancer, they have also been identified in breast, ovarian, colorectal, kidney, gallbladder, and bladder cancers as well as sarcomas. [4, 6]
Recently, the FDA has begun to recognize that some precision therapies that target oncogenic driver alterations may be “tumor-agnostic”, meaning they are likely to be effective no matter which organ the tumor is in.
Because NRG1 fusions are found in multiple solid tumors and are likely to be a unique oncogenic driver alteration whenever it is found, we are now testing seribantumab in this tumor-agnostic way.
Seribantumab is now being studied in patients with solid tumors of any origin that test positive for an NRG1 fusion. To find out if you may be eligible for our clinical trial with seribantumab, the first step is to get your tumor tested to discover if it carries an NRG1 fusion. We encourage you to learn more about our trial and talk to your physician about getting tested today.
 Data on File, Seribantumab Investigator’s Brochure, 2020
 Sequist LV et al., SHERLOC: A phase 2 study of MM-121 plus with docetaxel versus docetaxel alone in patients with heregulin (HRG) positive advanced non-small cell lung cancer (NSCLC). Journal of Clinical Oncology. 2019
 Fernandez-Cuesta L and Thomas RK., Molecular Pathways: Targeting NRG1 Fusions in Lung Cancer. Clinical Cancer Research. 2014
 Jonna et al., Detection of NRG1 gene fusions in solid tumors. Clin Cancer Res. 2019
 Dimou A and Camidge DR, Detection of NRG1 Fusions in Solid Tumors: Rare Gold?. Clinical Cancer Research. 2019
 Drilon A et al., Response to ERBB3-Directed Targeted Therapy in NRG1-Rearranged Cancers. Cancer Discovery. 2018
 Jones MR et al., NRG1 Gene Fusions are Recurrent, Clinically Actionable Gene Rearrangements in KRAS Wild-Type Pancreatic Ductal Adenocarcinoma. Clinical Cancer Research. 2019
 Shin DH et al., Oncogenic function and clinical implications of SLC3A2-NRG1 fusion in invasive mucinous adenocarcinoma of the lung. Oncotarget. 2016
 Arteaga CL and Engelman JA., ERBB Receptors: From Oncogene Discovery to Basic Science to Mechanism-Based Cancer Therapeutics. Cancer Cell. 2014