GenFleet bids to join the colorectal KRAS crowd
Competitors have given up on monotherapies in this use, but GenFleet wants to buck the trend.
Competitors have given up on monotherapies in this use, but GenFleet wants to buck the trend.
GenFleet Therapeutics could soon become only the third company with a KRAS G12C inhibitor in pivotal trials for colorectal cancer. On Friday the Chinese group said it had gained US go-ahead for a phase 3 study of its contender, fulzerasib, in patients progressed on at least two prior therapies.
The KRAS G12C space has become incredibly crowded, but there isn’t a huge deal of competition in colorectal cancer – at least not in phase 3 – beyond Bristol Myers Squibb’s Krazati, which is awaiting US approval, and Amgen’s Lumakras, which is to be filed this year. But there’s another aspect that could make GenFleet unique: fulzerasib will be tested in phase 3 as a monotherapy.
This is notable given that virtually every other KRAS G12C player has given up on monotherapies in colorectal cancer. GenFleet, however, cites a pooled analysis of two phase 1 trials in which fulzerasib yielded better single-agent response rate data than other monotherapy KRAS G12C inhibitors, and comparable results to combos with anti-EGFR MAbs, on a cross-trial basis.
Krazati is awaiting US colorectal cancer approval in combination with Erbitux, based on the Krystal-1 study, and has a 21 June PDUFA date for this use. Meanwhile, Lumakras plus Vectibix underwhelmed in Codebreak-300. In China GenFleet’s fulzerasib is licensed to Innovent.
KRAS G12C inhibitors in pivotal trials for colorectal cancer
| Drug | Trial | Design/setting | Note |
|---|---|---|---|
| Krazati (Bristol Myers Squibb) | Krystal-10 | Erbitux combo, vs chemo, 2nd-line+ | Filed based on ph1/2 Krystal-1 data; 21 June 2024 PDUFA date |
| Lumakras (Amgen) | Codebreak-300 | Vectibix combo, vs investigator’s choice, 2nd-line+ | Early data underwhelmed; US filing expected H1 2024 |
| Codebreak-301 | Vectibix + chemo combo, vs chemo +/- Avastin, 1st-line | Only pivotal KRAS G12C inhibitor trial in 1st-line colorectal cancer | |
| Fulzerasib (GenFleet) | TBC | Monotherapy, 3rd-line+ | FDA permission for ph3 received Apr 2024 |
| Glecirasib (Jacobio) | TBC | Erbitux combo | China trial, was to have started Q4 2023, now subject to design sign-off, expected Q2 2024 |
Source: OncologyPipeline.
Last year Jacobio Pharmaceuticals said a pivotal trial of glecirasib plus Erbitux in colorectal cancer would be initiated in China in the fourth quarter, but this has apparently yet to take place. And gleciracib’s most compelling data so far have come in pancreatic cancer, however.
Merck & Co’s MK-1084 has shown monotherapy promise in various solid tumours, but its phase 3 study, launched just this month, targets first-line non-small cell lung cancer.
Two other G12C inhibitors showed promise in colorectal cancer at last year’s ESMO conference: InventisBio’s garsorasib and Roche’s divarasib. However, these were both as part of Erbitux combinations, and neither company has revealed phase 3 plans in this cancer type.
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