After Revolution Medicine’s groundbreaking data drop in April, its Tango-partnered combination approach has demonstrated what analysts called “unprecedented” results for 12 patients with pancreatic cancer, teeing up a late-stage study.
Tango Therapeutics’ experimental PRMT5 inhibitor combined with Revolution Medicines’ RAS inhibitor achieved a 92% response rate in pancreatic cancer, a greater response than either have seen as monotherapies or in combination with chemotherapy.
“WOW!” Leerink Partners wrote in a Monday note forecasting Tango’s stock to at least double on the data. Sure enough, the biotech’s share price rose 43% as the markets opened Monday to $28.94. RevMed, which is up 88% year to date, rose just under 1% to $150.62.
“The results from our ongoing combination trial dramatically exceeded our expectations,” Tango CEO Malte Peters said on a Monday investor call. Given the data, Tango is queuing up registrational trial plans for the combination strategy in the front-line setting.
The findings come from an ongoing Phase 1/2 study of Tango’s vopimetostat and either RevMed’s zoldonrasib or daraxonrasib for patients with advanced MTAP-deleted and RAS-mutant metastatic pancreatic ductal adenocarcinoma (PDAC) or non-small cell lung cancer (NSCLC). Earlier this year, RevMed’s daraxonrasib alone doubled survival to 13.2 months in PDAC compared to chemotherapy, stunning the field in a disease that carries a 13% survival rate five years after diagnosis.
Now, Tango has topped that, sharing data from a dose-escalation arm in which patients every day received either vopimetostat 200 mg or 250 mg, plus daraxonrasib 100 mg. Of 12 PDAC patients with 14 weeks of follow up, 92% (11 patients) saw an objective response rate, with nine confirmed responses. The data also demonstrated 100% disease control rate for the 12 patients, plus a 90% six-month progression-free survival (PFS) rate.
“The efficacy results speak for themselves,” Leerink Partners analysts wrote, underscoring “unprecedented activity” in the second-line setting and suggesting “strong synergy” between the paired agents in both response rate and durability.
When considering the three evaluable patients with NSCLC, 100% achieved an objective response rate at a minimum of 14 weeks follow up. While “encouraging,” Leerink analysts said the data were “still too limited in scope,” to forecast longer-term success.
The combination of vopimetostat and zoldonrasib achieved a 52% ORR with 14 patients responding and a 74% PFS rate.
In terms of safety, Tango said the investigational combination approach was generally well-tolerated, with no new safety signals reported. Zero patients discontinued treatment because of adverse events, and no grade 4 or 5 events occurred. The 100-mg daraxonrasib dose is lower than RevMed’s monotherapy level of 300 mg and chemo combo of 200 mg, which could suggest a possible drug interaction or overlapping toxicities, Leerink noted.
Tango now hopes to speed into Phase 3 development in first-line MTAP-deleted pancreatic cancer and indicated that it would consider moving forward in second-line treatment as well, pending regulatory feedback.
“Given the unprecedented activity seen in PDAC, a terminal disease with limited treatment options, we think the FDA would be hard-pressed to deny such a request,” Leerink wrote.
