Tango Therapeutics and Erasca have begun enrolment for a Phase I/II trial assessing the combination of oral therapies ERAS-0015 and vopimetostat in patients with lung and pancreatic cancers.
The multi-centre, open-label trial focuses on individuals diagnosed with methylthioadenosine phosphorylase (MTAP)-deleted pancreatic ductal adenocarcinoma, alongside patients with MTAP-deleted and rat sarcoma virus (RAS)-mutant non-small cell lung cancer.
It is sponsored by Tango Therapeutics and consists of dose-escalation and expansion phases.
The dose-escalation phase primarily aims to identify the combination’s maximum tolerated dose.
Secondary measures include evaluating safety, tolerability, pharmacokinetics, and antitumour activity.
Tango Therapeutics president and CEO Malte Peters said: “The encouraging clinical activity, durability and tolerability observed to date with vopimetostat in combination with RAS inhibition reinforce our belief that co-targeting PRMT5 and RAS represents a promising new frontier in the treatment of pancreatic cancer and potentially other RAS-driven cancers.
“We are thrilled to initiate this study in partnership with Erasca, a company leading the advancement of RAS-targeted therapies, to evaluate vopimetostat with ERAS-0015 and further explore the potential of this clinically validated and synergistic combination approach.”
Both investigational therapies target cancer pathways through distinct mechanisms.
ERAS-0015 is an oral pan-RAS molecular glue created to block RAS signalling and counter resistance to mutant-selective inhibitors by suppressing RAS wild-type variants.
Erasca is currently assessing the therapy in the AURORAS-1 Phase I trial for patients presenting with RAS-mutant solid tumours.
Initial dose escalation demonstrated linear pharmacokinetics alongside confirmed and unconfirmed partial responses at doses starting at 8mg once daily.
Vopimetostat is a once-daily oral protein arginine methyltransferase 5 (PRMT5) inhibitor evaluated by Tango Therapeutics as both a monotherapy and in combination.
In clinical evaluations to date, the therapy showed durable activity and a favourable tolerability profile across several MTAP-deleted cancers, including pancreatic and lung malignancies.
