#AS­CO21: Gilead­'s Trodelvy reads out new sub­group da­ta show­ing ben­e­fit in ear­li­er-line TNBC pa­tients

With As­traZeneca and Dai­ichi sniff­ing at its trail, Gilead has worked hard to hold an ad­van­tage for ADC Trodelvy in par­tic­u­lar­ly hard-to-treat breast can­cer pa­tients. Now, the drug­mak­er is read­ing out more late-stage da­ta show­ing some ben­e­fit in ear­li­er-line pa­tients, and it could help carve a path for­ward to a big­ger mar­ket share.

Gilead’s Trodelvy ex­tend­ed sur­vival in a sub­group analy­sis of re­lapsed or re­frac­to­ry triple-neg­a­tive breast can­cer pa­tients in the sec­ond line, a pos­i­tive sign Gilead hopes could spell ear­li­er lines of ther­a­py for its TROP2-di­rect­ed ADC, ac­cord­ing to da­ta from the Phase III AS­CENT study set to be pre­sent­ed at this week­end’s #AS­CO21.

Trodelvy re­ceived a full ap­proval from the FDA in April to treat metasta­t­ic TNBC pa­tients in the sec­ond line or lat­er as well as an ac­cel­er­at­ed nod in urothe­lial car­ci­no­ma the same month.

In sec­ond-line pa­tients who re­port­ed dis­ease pro­gres­sion with­in 12 months of (neo)ad­ju­vant chemo. Trodelvy cut the risk of dis­ease wors­en­ing or death by 59% over chemo with a PFS of 5.7 months com­pared with 1.5 months on chemo. The ther­a­py al­so post­ed a me­di­an OS of 10.9 months com­pared with 4.9 months for pa­tients on chemo.

Trodelvy al­so showed a high­er over­all re­sponse rate com­pared with chemo — 30% com­pared with 3% — and a safe­ty pro­file in the sub­group that was con­sis­tent with oth­er stud­ies, Gilead said. There were no treat­ment-re­lat­ed deaths in the sub­group.

Read­ing out in ear­li­er lines of ther­a­py will be a ma­jor fo­cus point for Gilead as it looks to build its lead over As­traZeneca and Dai­ichi Sankyo, which are look­ing for ap­proval for a TROP2-di­rect­ed ADC of their own.

In ear­ly May, the part­ners read out Phase I co­hort da­ta for their next-gen ADC datopotam­ab derux­te­can show­ing a 43% re­sponse rate and five con­firmed com­plete or par­tial re­spons­es among 21 pa­tients with TNBC. The vast ma­jor­i­ty of those pa­tients were treat­ed with 6-mg dos­es of the drug while two re­ceived an 8-mg high dose. On top of the five con­firmed re­spons­es, the part­ners were await­ing con­fir­ma­tion on four ad­di­tion­al re­spons­es at the Jan. 8 cut­off date. Datopotam­ab post­ed a dis­ease con­trol rate of 95%.

Gilead won a full ap­proval for Trodelvy in TNBC based on the strength of AS­CENT, which showed Trodelvy re­duced the risk of death in TNBC pa­tients by 49%, with a me­di­an OS of 11.8 months, as op­posed to the 6.9 months achieved by stan­dard sin­gle-agent chemother­a­py. PFS came in at a me­di­an of 4.8 months, com­pared to 1.7 months on chemother­a­py.

What Will it Take to Re­al­ize the Promise and Po­ten­tial of Im­mune Cell Ther­a­pies?

What does it take to get to the finish line with a new cancer therapy – fast? With approvals in place and hundreds of immune cell therapy candidates in the pipeline, the global industry is poised to create a fundamental shift in cancer treatments towards precision medicine. At the same time, unique challenges associated with cell and process complexity present manufacturing bottlenecks that delay speed to market and heighten cost of goods sold (COGS) — these hurdles must be overcome to make precision treatments an option for every cancer patient. This series of articles highlights some of the key manufacturing challenges associated with the production of cell-based cancer therapies as well as the solutions needed to transcend them. Automation, process knowledge, scalability, and assured supply of high-quality starting material and reagents are all critical to realizing the full potential of CAR-based therapies and sustaining the momentum achieved in recent years. The articles will highlight leading-edge technologies that incorporate these features to integrate across workflows, accelerate timelines and reduce COGS – along with how these approaches are enabling the biopharmaceutical industry to cross the finish line faster with new treatment options for patients in need.

The biggest ques­tions fac­ing gene ther­a­py, the XLMTM com­mu­ni­ty, and Astel­las af­ter fourth pa­tient death

After three patients died last year in an Astellas gene therapy trial, the company halted the study and began figuring out how to safely get the program back on track. They would, executives eventually explained, cut the dose by more than half and institute a battery of other measures to try to prevent the same thing from happening again.

Then tragically, Astellas announced this week that the first patient to receive the new regimen had died, just weeks after administration.

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As­traZeneca touts Imfinzi im­munother­a­py com­bos for lung can­cer in push to dri­ve PD-L1 drug up­take

Facing the big dogs in the PD-(L)1 space, AstraZeneca has taken its own contender Imfinzi into blockbuster territory in its four years on the market but sees even bigger things for the drug. Combinations could be the key, and early results from a mid-stage test are adding some fuel to that strategy.

Imfinzi combined with one of two investigational immunotherapies — a CD73 antibody dubbed oleclumab or an anti-NGK2a named monalizumab — topped Imfinzi alone in terms of overall response and progression-free survival in patients with stage III non-small cell lung cancer whose tumors had not worsened during concurrent chemoradiation, according to interim data from the Phase II COAST trial set to be presented at #ESMO21.

Amgen VP of R&D David Reese

Am­gen rolls out da­ta for KRAS in­hibitor com­bo study in col­orec­tal can­cer, hop­ing to move on from ug­ly ear­ly re­sults

With the first win for its KRAS inhibitor sotorasib in hand, Amgen is pushing ahead with an aggressive clinical plan to capitalize on its first-to-market standing. The drugmaker thinks combinations — in-house or otherwise — could offer a path forward, and one early readout from that strategy is bearing fruit.

A combination of Amgen’s sotorasib and its EGFR inhibitor Vectibix posted an overall response rate of 27% in 26 patients with advanced colorectal cancer (CRC) with the KRAS-G12C mutation, according to data from the larger Phase Ib/II CODEBREAK 101 study set to present at this weekend’s virtual ESMO Congress.

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Gri­fols drops $1B on Ger­man hold­ing com­pa­ny in con­tin­ued plas­ma push

One Spanish biotech is beefing up its plasma therapy operations, and on Friday, it announced that it’s doing so in a billion-dollar deal.

Grifols is now the largest shareholder of Biotest, a company valued at more than $1.8 billion. By teaming up, the two will try to increase the number of plasma therapies available and increase patient access around the world, Grifols said in a press release.

The company did so by acquiring holding company Tiancheng Pharmaceutical, the Germany-based owner of nearly 90% of Biotest shares, for nearly $1.27 billion. Grifols now owns nearly 90% of Biotest voting rights and almost 45% of the total share capital of Biotest.

Dan O'Day, Gilead CEO (Jim Watson/AFP via Getty Images)

Eu­ro­pean study finds that Gilead­'s Covid-19 an­tivi­ral remde­sivir shows no clin­i­cal ben­e­fit

Gilead’s remdesivir — or Veklury, as it’s marketed in the US — raked in around $2.8 billion last year as the only FDA-approved antiviral to treat Covid-19. But new data from a European study suggest the drug, which has been given to about half of hospitalized Covid patients in the country, has no actual benefit.

The open-label DisCoVeRy trial enrolled Covid-19 patients across 48 sites in Europe to test a handful of treatments, including remdesivir, lopinavir–ritonavir, lopinavir–ritonavir and interferon beta-1a, and hydroxychloroquine. To participate, patients had to show symptoms for seven days and require oxygen support. A total of 429 patients were randomized to receive remdesivir plus standard of care, while 428 were assigned to standard of care alone.

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Covid-19 roundup: FDA re­veals boost­er ad­comm ques­tion; Eli Lil­ly's an­ti­body cock­tail cleared for pre­ven­tion

The FDA released briefing documents this week from the agency and Pfizer each outlining their arguments for today’s Covid-19 booster shot adcomm, but one thing conspicuously missing was the question on which panel members would be voting. But late Thursday night, regulators published that question.

Adcomm members will be asked whether or not the safety and efficacy data from Pfizer/BioNTech’s original Phase III study “support approval” of a booster shot at least six months after the second dose in individuals older than 16. The question notably excludes the real-world data from Israel and other analyses that Pfizer and the Biden administration had said would be a centerpiece of their arguments for boosters.

A Pfiz­er part­ner wel­comes ex-ADC Ther­a­peu­tics CMO Jay Fein­gold to the team; Amid tough sled­ding, Im­muno­vant choos­es Eli Lil­ly alum as CFO

→ Last week we told you about the CMO revolving door at ADC Therapeutics, as Joseph Camardo replaced the departing Jay Feingold. The next opportunity for Feingold in the CMO slot has opened up at antibody-drug conjugate and mAb developer Pyxis Oncology, which has added several new execs and scientific advisory board members in recent months, including ex-Immunovant CFO Pamela Yanchik Connealy. Before his tenure at ADC, Feingold was Daiichi Sankyo’s VP of US medical affairs and chairman of the Global Medical Affairs Oversight Committee. Within weeks in March, Pyxis struck a licensing deal with Pfizer for two of its ADCs and raked in $152 million from a Series B round.

Ali Tehrani, Zymeworks CEO

Zymeworks squares up with Her­ceptin af­ter HER2 bis­pe­cif­ic aces mid-stage test in esophageal can­cer

Roche’s Herceptin has long stood as standard of care across multiple advanced cancers, but a suite of next-gen players are looking to beat the aging giant at its own game. In HER2-expressing esophageal cancer, BeiGene partner Zymeworks thinks its bispecific antibody could have the juice to get it done.

Zymeworks’ bispecific antibody zanidatamab, combined with one of two chemotherapy regimens, posted an overall response rate of 75% in patients with advanced gastroesophageal adenocarcinoma (GEA) who had not previously received a HER2-targeted cancer therapy, the Vancouver-based biotech said Thursday.