$150,000 Grant to MSK for New Ewing Sarcoma Combination Trial
Heidi (left), Tim (right) and Gus (center) of the #GusTough Frank Family present the grant to Emily Slotkin, MD, and Talia Sauerhaft, NP of Memorial Sloan Kettering.
UPDATE: NOW OPEN (as of 3/3/22). Identifier: NCT05275426 For more information please reach out to the intake coordinators at MSK by calling 833-MSK-KIDS, and reference Dr. Slotkin as lead PI and mention the new low-dose Gemcitabine & CHK1 Inhibition phase II clinical trial.
We’re continuing to run at full speed in 2022 and are excited to announce a grant to Memorial Sloan Kettering (MSK) for $150,000 to help support the opening of a phase II clinical trial for Ewing and Ewing-like sarcoma.
This clinical trial will test the therapeutic efficacy of combining low-dose Gemcitabine (Gem) chemotherapy with a targeted checkpoint kinase 1 (CHK 1) inhibitor, labelled as LY2880070. Esperas Pharma, Inc. has committed to providing this drug for this trial.
Ewing Sarcoma (EwS) cells inherently have a dysregulated growth pattern and consequently are prone to high levels of endogenous replication stress. In response, EwS cells compensate by activating a mechanism called the replication stress response (RSR), which promotes continued viability and proliferation of these cells. Fortunately for us, this same compensating stress response is a rare moment of weakness for EwS cells, as these mechanisms are druggable targets.
In this clinical trial, low-dose Gem exacerbates replication stress by further applying exogenous DNA damage to the cell (a secondary stress), forcing EwS cells to become more dependent on the CHK1 repair mechanism (a RSR). By combining this replication stress with a block on it’s repair mechanism (via CHK 1 inhibition), creates a two-pronged therapeutic approach that acts synergistically.
In addition, Ewings-like sarcomas such as CIC-DUX4 (which as a whole is less chemotherapy responsive) has been discovered to be highly reliant on a RSR, and sensitive to these targeted therapies in preclinical testing. This trial could be an intriguing therapeutic approach for this subgroup population that drastically needs a viable treatment option.
Lastly (though this is not an inclusion criterion), EwS tumors that also harbor STAG2 mutations are theorized to yield high sensitivity to CHK1 inhibition. STAG2 mutations are often a biomarker of advanced disease and poor prognosis, with few treatment options available for this sub-population.
This trial is “open label”, meaning there isn't a placebo arm. CHK1 inhibitor dosing is at therapeutic dosing level (phase II). And over the course of a 21-day cycle, patients will receive pulsed on/off intravenous Gem chemo paired with the oral CHK1 inhibitor.
Inclusion criteria for this clinical trial include:
for relapsed/refractory Ewing or Ewing-like sarcoma (confirmed at MSK)
adolescents who weigh at least 40 kg (~88 lbs)
less than 4 lines of prior therapy (prior Gem treatment is acceptable)
min. blood counts of ANC > 1500, Platelet > 100,000 and Hemoglobin > 8.0
Suffice it to say we are grateful for Emily Slotkin's (MD) diligence and work to open this clinical trial for kids / adolescents with EwS. This clinical trial is opening soon at MSK. The only rate limiting step holding back this trial from moving forward, is the shipment of the LY2880070 drug from Ireland (more complicated than you would believe).
Thanks to the following donor-directed warrior families for providing financial support of this trial through LWF: the Gus Tough Frank Family and the Friedman / Morrison Family.
Swords Up Little Warriors!