Gastric adenoma

Astellas Pharma’s claudin 18.2-directed cytolytic antibody has been approved by the European Commission (EC) as part of a first-line combination treatment for a subset of gastric cancer patients. Vyloy (zolbetuximab) has been authorised for use alongside fluoropyrimidine- and platinum-containing chemotherapy to treat adults with locally advanced unresectable or metastatic human epidermal growth factor receptor 2 (HER2)-negative gastric or gastro-oesophageal junction (GEJ) adenocarcinoma whose tumours are claudin 18.2 positive. The European Medicines Agency (EMA) has also recommended that the drug’s designation as an orphan medicinal product be maintained due to the poor survival outcomes associated with gastric and GEJ cancers. Approximately 136,000 people are diagnosed with gastric cancer every year in Europe and adenocarcinomas, which develop from cells in the innermost lining of the stomach, account for the majority of cases. The disease usually develops slowly over many years and early-stage symptoms frequently overlap with more common stomach-related conditions, causing most cases to go undetected until an advanced or metastatic stage. Administered as an infusion every two to three weeks, Vyloy is now the first and only therapy approved in the EU specifically designed to target gastric tumour cells that express the biomarker claudin 18.2. The approval follows a recent recommendation from the EMA’s human medicines committee and was supported by results from the phase 3 SPOTLIGHT trial, which evaluated first-line Vyloy plus mFOLFOX6 – a combination regimen that includes oxaliplatin, leucovorin and fluorouracil – versus placebo plus mFOLFOX6 in patients with claudin 18.2-positive, HER2-negative, locally advanced unresectable or metastatic gastric or GEJ adenocarcinoma. A median progression-free survival of 10.61 months was achieved with the Vyloy regimen compared with 8.67 months for placebo plus mFOLFOX6, while median overall survival was 18.23 months versus 15.54 months in the respective treatment groups. The regulator’s decision was also informed by positive results from the late-stage GLOW study, which assessed Vyloy alongside CAPOX – a combination chemotherapy regimen that includes capecitabine and oxaliplatin – in the same patient population. Moitreyee Chatterjee-Kishore, senior vice president and head of immuno-oncology development at Astellas, said the company was “delighted” to bring Vyloy to patients in Europe, adding that it is now “entering a new era in precision medicine for these advanced cancers”.

In 2022, IDRx raised $122m in Series A financing and licensed two TKI inhibitors – IDRX-42 from Merck KGaA, and IDRX-73 from Blueprint Medicines. Image credit: Mr.Boyz / Shutterstock. US-based precision therapeutics company IDRx has raised $120m in a Series B financing round to fund the clinical development of its lead oncology candidate, IDRX-42. The preferred stock financiers included multiple US investment companies such as RA Capital Management, Commodore Capital, and Blackstone Multi-Asset Investing. The company plans to use the proceeds to finance the ongoing Phase I trial and start a pivotal trial evaluating the therapy in patients with gastrointestinal stromal tumours (GIST). IDRX-42 is a selective tyrosine kinase inhibitor (TKI). IDRx licensed the therapy from Merck KGaA in 2022. It has received an orphan drug designation for the treatment of GIST from the US Food and Drug Administration (FDA). The ongoing Phase I StrateGIST 1 trial (NCT05489237) is evaluating the safety and tolerability of IDRX-42 in patients with metastatic and/or surgically unresectable GIST after the failure of Novartis ’ Gleevec/Glivec (imatinib mesylate) and other approved drugs. In June, the company reported positive preliminary data from the study showing a 23% objective response rate (ORR) across all patients who received a median of four prior lines of therapy. An ORR of 43% was seen in patients receiving IDRX-42 as a second-line treatment, of which all were partial responses. See Also: Takeda’s ADZYNMA gains EU approval for cTTP treatment Amneal’s CREXONT gains FDA approval for Parkinson’s treatment Commonly observed side effects were Grade I gastrointestinal symptoms. Three out of the 63 patients experienced dose-limited toxicities, which were resolved, and patients elected to reduce dosages. IDRx’s pipeline also consists of another TKI, IDRX-73, which the company licensed from Blueprint Medicines . TKIs have been effective in treating various cancers. AstraZeneca ‘s Tagrisso (osimertinib) is approved for treating non-small cell lung cancer and generated $5.8bn in sales last year, as per the company’s financials. Gleevec/Glivec is a top 20 highest-grossing drug for Novartis, and raked in $561m in sales in 2023, as per the company’s financials. It has not been smooth sailing for all TKIs. In October 2023, Takeda Pharmaceutics issued a voluntary withdrawal of Exkivity (mobocertinib) in the US after a confirmatory Phase III trial failed to meet its primary endpoint.

Surface Oncology is letting go of 20% of its workforce as the biotech prunes its pipeline and narrows the scope of its lead drug. The Boston-area cancer drug developer is looking for external partners on its CD39 asset, dubbed SRF617, after a strategic review, which the company said would extend runway into the second quarter of 2024, with burn historically being about $20 million per quarter. On the sidelines of ASCO this June, CEO Rob Ross told Endpoints News the asset was one of the biotech’s two “crown jewels” and hinted that a partner would likely be needed. But Wednesday’s news, disclosed in the quarterly update, is perhaps a little earlier than expected. “We’re very focused on moving them forward ourselves,” Ross told Endpoints in June, referring to ‘617 and lead drug SRF388. “Having said that, I think it would be hubris and a little ridiculous for me to say that we would not partner. In fact, for small biotech, at some partnership, particularly in I/O, becomes super important, so we’re always talking with everyone we both can name and talking through the data and thinking about whether or not a partnership gets this drug to patients more quickly. And at some point, the answer to that is going to be ‘Yes.’” On an investor call Wednesday morning, Ross said the next steps for the culled asset would likely have been a Phase II combination study, given the lack of signals seen with monotherapy data to date. The original vision included treating patients with gastric, prostate, pancreatic and PD-(L)1 relapsed cancers. Also getting adjusted is lead asset SRF388, which Ross said on the call is the only IL-27-targeting antibody in the clinic as far as the biotech is aware. Surface has decided to focus the ongoing Phase II trial on lung and liver cancers, and end an arm looking at a subset of kidney cancer. With those updates, Surface is laying off one-fifth of its workforce, which stood at 67 employees at the end of February. Of those, 45 were involved in R&D. On the call, Ross said affected employees are getting “extensive support.” “Once a surfer, always a surfer,” the CEO added. Meanwhile, the company wants to go up against Big Pharma in chemokine receptor 8, or CCR8. Surface will start dosing patients in a Phase I study of SRF114 soon, as the FDA cleared the IND last month. Ross said he believes Surface will be about the fourth to enter the clinic, following Gilead, Shionogi and Bristol Myers Squibb. Gilead paid out another $15 million to its CCR8 partner Jounce Therapeutics, the biotech said Wednesday, as part of their overall $805 million September 2020 agreement for GS-1811, which is currently in Phase I for advanced solid tumors. Five Prime Therapeutics had also been conducting preclinical work on an anti-CCR8 antibody prior to being swept into the Amgen fold . FibroGen also waded into the space last year in a pact with HiFiBiO . A handful of others want to enter the clinic, as well: Texas-based iBio, Coherus BioSciences, Zai Lab and others.