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Roche trims its pipeline again

Belvarafenib heads back to Hanmi and LY6G6D targeting takes a blow.

Roche has been on a culling spree of late, and during today's first-quarter results it revealed that two more early-stage oncology projects have bitten the dust: the Hanmi-originated pan-RAF inhibitor belvarafenib and the anti-LY6G6D T-cell engager RG6286.

No clinical data are available on the latter, which had been in a phase 1 trial in colorectal cancer due to complete in early 2026. But results have been released on belvarafenib, which had been tested in various solid tumours, with a focus on NRAS-mutant melanoma.

Dose-limiting toxicities

A Hanmi-sponsored trial of belvarafenib plus Cotellic, Rafi-103, was presented at ASCO 2021, showing a response rate of 39% among 13 melanoma patients, most of whom had previously been treated with checkpoint inhibitors. However, there were three dose-limiting toxicities among the 32-patient safety cohort.

Meanwhile, last year’s ESMO meeting detailed a 60% response rate from the same study among 15 patients with various tumours with BRAF fusions. However, there were no responses in eight subjects with BRAF class II/III point mutations.

Roche had been evaluating belvarafenib plus Cotellic with or without Opdivo in NRAS-mutant melanoma, and there had also been a belvarafenib arm in its Tapistry platform trial. A spokesperson confirmed that enrolment had now stopped, and that the company had removed belvarafenib from its portfolio.

The Swiss group's move comes the same day as the approval of another pan-RAF inhibitor, Day One's Ojemda; however, that green light came in the much less well served setting of paediatric low-grade glioma. 

At the time of publishing Hanmi had not responded to questions about whether it planned to continue alone with the project.

Lonely LY6G6D

Meanwhile, Roche’s hopes of targeting the protein LY6G6D to treat patients with microsatellite stable (MSS) or low microsatellite instability (MSI-L) colorectal cancer have come to nothing.

QLSF Biotherapeutics’ is also taking aim at MSS colorectal cancer with its rival T-cell engager QL335, which now appears to be the only project hitting LY6G6D, according to OncologyPipeline. Preclinical data on that asset featured at this year’s AACR meeting, and a phase 1 trial is ongoing, according to the company.

Today, Roche also highlighted its discontinuation of Repare’s ATR inhibitor camonsertib, which was previously disclosed. In the past six months the group says it's terminated 20% of the NMEs in its pipeline in a drive for best/first in class, though it stressed to analysts that this was a gross figure.

With the Swiss company looking increasingly ruthless, investors will be waiting to see whether more projects fall into the firing line.


Roche oncology assets discontinued in Q1 2024

BelvarafenibPan-RAF inhibitorSolid tumoursPh1 + Cotellic +/- Opdivo in NRASm melanoma; belvarafenib arm in tumour-agnostic Tapistry
RG6286 (BLYG8824A )LY6G6D T-cell engagerColorectal cancerPh1 with focus on MSS/MSI-L
CamonsertibATR inhibitorSolid tumoursAlready disclosed; originator Repare to determine future steps

Source: Roche Q1 2024 earnings presentation.