Incyte has pointed to a spread of phase 1 data for its KRAS G12D inhibitor as proof that the company has a worthy rival to Revolution Medicines in this newly hot cancer space.
Across three oral presentations at the European Society for Medical Oncology congress in Madrid, Incyte updated attendees on its cancer pipeline, including early-stage data on its KRAS G12D inhibitor, dubbed INCB161734, in patients with pancreatic ductal adenocarcinoma (PDAC).
Among 28 patients who received INCB161734 in combination with the chemotherapy regimen modified FOLFIRINOX, the treatment achieved a confirmed objective response rate (ORR) of 81% and a disease control rate (DCR) of 100%, according to data from a July cutoff.
In addition, the six-month progression-free survival (PFS) rate for these patients was 90%. The most common treatment-related adverse events (TRAEs) included diarrhea (which affected 67.9% of patients), nausea (64.3%), vomiting (57.1%) and decreased neutrophil count (57.1%).
The trial also tested INCB161734 in combination with a different chemotherapy regimen, gemcitabine and nab-paclitaxel, in 26 patients. That combination achieved a confirmed ORR of 58%, a DCR of 96% and a six-month PFS rate of 80%. The TRAE profile was broadly similar.
Incyte President and Global Head of R&D Pablo Cagnoni, M.D., told Fierce that the disparity between the ORRs in the two arms of the study was likely due to the different chemotherapies used.
“If you look at the RevMed data, they also have better response for FOLFIRINOX,” said Cagnoni, referencing that company’s own KRAS G12D contender, zoldonrasib.
RevMed made headlines in August when it secured FDA approval for its RAS inhibitor Rasonque as a pill for patients with metastatic pancreatic adenocarcinoma who had received prior treatment or were not candidates for multiagent systemic therapy. While Rasonque targets multiple RAS mutations, zoldonrasib specifically targets RAS G12D, with the biopharma reporting an 82% ORR when the drug was combined with modified FOLFIRINOX in previously untreated patients with metastatic pancreatic cancer at this year's ESMO Gastrointestinal Cancers Congress.
While zoldonrasib targets the “ON” state of RAS G12D, Incyte’s INCB161734 is an “ON/OFF” inhibitor. Despite these differences, Cagnoni sees the two drugs as broadly comparable.
“Honestly, when I look at the data side by side, I think they're similar,” Cagnoni told Fierce during an interview on the conference sidelines.
“I won't try to convince you we're better,” he added. “I am pretty certain we're no worse. I think we're neck and neck.”
Incyte has already kicked off a global phase 3 trial of INCB161734 alongside chemotherapy in first-line metastatic PDAC, with topline data anticipated in 2028. The company also has plans for a separate phase 3 trial in the adjuvant setting. Meanwhile, RevMed has launched its own late-stage study of zoldonrasib in combination with chemotherapy for pancreatic cancer.
“The way I see the space now, [Incyte and RevMed] are going to be in the front,” Cagnoni said. “Everybody else is far behind, and I haven't seen any data set from anyone that looks clearly better than us.”
At ESMO, Incyte also served up data on INCB161734 in 49 patients with advanced or metastatic colorectal cancer. Among 22 heavily pretreated patients who received INCB161734 alongside the cancer therapy Erbitux, the combination achieved an ORR of 36%, a DCR of 100% and a median PFS of 7.2 months.
The company is gearing up to launch a late-stage study of INCB161734 and Erbitux in colorectal cancer next year. During ESMO, Incyte also revealed a collaboration with Genmab to test INCB161734 alongside the Danish biopharma's EGFR- and LGR5-targeting bispecific antibody petosemtamab and chemotherapy in the first-line setting.
In addition, Incyte showcased its latest findings for INCA33890, a TGFβR2×PD-1 bispecific antibody, given alongside standard-of-care therapies in a phase 1 trial for metastatic microsatellite-stable colorectal cancer.
Among 42 patients who received INCA33890 in combination with the chemotherapy regimen FOLFOX and Roche’s Avastin as a first-line treatment, Incyte reported an ORR of 71.4%, a DCR of 100% and a six-month PFS rate of 81.4%.
With Incyte’s blockbuster JAK inhibitor Jakafi set to lose patent exclusivity in 2028, the KRAS readouts are “a key part of that story” of how the company future-proofs its business, according to Cagnoni.
Part of the strategy is to “grow the non-Jakafi core business,” he said, name-checking the JAK inhibitor Opzelura, the upcoming FDA decision on povorcitinib for hidradenitis suppurativa, the blood cancer drug Monjuvi and the graft-versus-host disease treatment Niktimvo.
“It's a series of products that, when you stack them, should deliver about three [to] three-and-a-half-billion dollars in sales by 2029, which is the first non-Jakafi year,” Cagnoni explained.
“From there, what we have is a pipeline that we've been talking about that should deliver double-digit growth starting in 2031,” he added. This portfolio includes planned launches of INCB161734 in both pancreatic and colorectal cancer, alongside other assets such as a phase 3-stage CDK2 inhibitor for ovarian cancer.