Triple meeting 2025 – early efficacy signs for Quanta

Until now, development of KRAS G12D-targeting projects has largely focused on pancreatic and lung cancers, but Quanta’s “G12D-preferring” multi-KRAS inhibitor QTX3034 has produced responses in endometrial and colorectal cancers, as well as pancreatic, the Triple meeting heard on Friday.

The endometrial responses came with QTX3034 monotherapy, while the colorectal and pancreatic responders had been treated with an Erbitux combo. With data on only a handful of patients so far, it’s tricky to gauge how the project stacks up against its G12D rivals, but balanced against a relatively low incidence of high-grade adverse events, QTX3034 looks worth pursuing.

However, one reason for caution is a lack of responses in pancreatic cancer among eight patients receiving monotherapy at the go-forward dose of 1,200mg twice daily. Other G12D-targeting agents have produced ORRs of 25-41% as monotherapy in relapsed pancreatic cancer, with data on contenders from Incyte, Genfleet/Verastem and Jiangsu HengRui recently presented at ESMO.

Instead, the US-based phase 1 trial of QTX3034, in pretreated G12D-mutated solid tumours, reported two confirmed responses among three endometrial cancer patients receiving 1,200mg twice daily. As well as the eight pancreatic and three endometrial patients, there were four patients with undisclosed "other" cancers, among whom no responses were seen.

In the same study, Erbitux plus QTX3034 1,200mg twice daily led to three confirmed responses among 12 patients, two in pancreatic ductal adenocarcinoma (seven patients treated), and one in colorectal cancer (five patients treated). There was also an unconfirmed response in the colorectal cohort.

First data on Quanta’s QTX3034

Notes: Cutoff: 23 Sep 2025; data for QTX3034 1,200mg BID; *both responses in endometrial cancer & additional endometrial CR at 800mg BID; **cORR + uORR 33% (4/12). Source: EORTC-NCI-AACR 2025. 

EGFR inhibitors like Erbitux have been combined with KRAS G12C inhibitors, but these are the first data with a G12D/EGFR combo, according to Quanta.

Adverse events with the combo looked more troublesome than with QTX3034 alone, with 25% of combo-treated patients experiencing grade 3 or higher adverse events, versus none in the 1,200mg twice-daily monotherapy group. The most common adverse events were nausea, vomiting and diarrhoea and, although mostly grade one, a vomiting rate approaching 70% seems fairly high.

Dose expansion is ongoing in endometrial, colorectal and pancreatic cancers, and privately-held Quanta plans to test QTX3034 in combination with other agents, including alongside chemo in front-line disease.

Incyte is focused on INCB161734 plus chemo in first-line pancreatic cancer, and a pivotal trial could start in 2026. That group is also looking at various combos in colorectal cancer, including with Erbitux and its TGFβR2 x PD-1 bispecific INCA33890.

Verastem’s first Western data

Meanwhile, separately from the Triple (EORTC-NCI-AACR) symposium, Verastem has reported the first update from a US phase 1/2 trial of VS-7375 (GFH375), a G12D inhibitor licensed from China’s GenFleet, although details are thin on the ground.

The company merely noted that the first two monotherapy dose levels, 400mg and 600mg daily, have been cleared, with no dose-limiting toxicities reported. As for efficacy, Verastem only said that of five evaluable patients with at least one scan, four have had a tumour reduction and are still on treatment. At the time of publication, the company hadn’t replied to a question about whether any of these amounted to complete or partial responses.

Dose escalation continues to 900mg once daily, and the trial is also now enrolling an Erbitux combo cohort in solid tumours including colorectal cancer. The next update from this trial is due in the first half of 2026.