Tecen­triq pass­es neoad­ju­vant breast can­cer tri­al as Roche looks for ear­ly start on the next big check­point op­por­tu­ni­ty

Shot through hun­dreds of tri­als over the last decade, check­point in­hibitors have proven a ver­sa­tile tool. First ap­proved for melanoma, col­lec­tive­ly they now cov­er dozens of can­cer types and set­tings, earn­ing their de­vel­op­ers bil­lions in the process.

Large­ly, though, they have avoid­ed use in one of the most com­mon set­tings: Lo­cal­ized tu­mors typ­i­cal­ly treat­ed with ad­ju­vant or neo-ad­ju­vant ther­a­py. For drug com­pa­nies, Cowen es­ti­mat­ed last Oc­to­ber, it’s a po­ten­tial $110 bil­lion mar­ket, one they’re rapid­ly try­ing to fill. The firm not­ed a long list of tri­als were un­der­way and due to start read­ing out — for breast can­cer at least —  this Sep­tem­ber with a Roche study in neoad­ju­vant-stage triple-neg­a­tive breast can­cer.

That tri­al has now read out ahead of ex­pec­ta­tions. And the re­sults, Roche’s biotech sub­sidiary Genen­tech said, are pos­i­tive.

Known as IM­pas­sion031, the Phase III study en­rolled ear­ly-stage triple-neg­a­tive breast can­cer pa­tients who were sched­uled for surgery and gave them ei­ther Roche’s PD-L1 ther­a­py Tecen­triq plus the chemother­a­py Abrax­ane or sim­ply chemother­a­py alone. The ques­tion was whether pa­tients tak­ing Tecen­triq were more like­ly to have a patho­log­i­cal com­plete re­sponse — i.e. were more like­ly to show no signs of tu­mor tis­sue when they went in for surgery.

The an­swer was yes, Roche said, though da­ta have yet to be re­leased. The study be­gan in 2017 and aimed to en­roll 324 pa­tients, ac­cord­ing to clin­i­cal­tri­als.gov. The ben­e­fit was seen re­gard­less of whether a pa­tient was PD-L1 pos­i­tive, Roche said.

Last year, Tecen­triq be­came the first im­munother­a­py ap­proved for triple-neg­a­tive breast can­cer — a com­mon tu­mor type that has long elud­ed ad­vanced ther­a­pies be­cause pa­tients’ tu­mors don’t ex­press high quan­ti­ties of the re­cep­tors tar­get­ed drugs go af­ter. That ap­proval, though, was on­ly for metasta­t­ic pa­tients who are PD-L1 pos­i­tive.

Among check­point in­hibitors, Roche has tra­di­tion­al­ly lagged be­hind Mer­ck’s Keytru­da and Bris­tol My­ers Squibb’s Op­di­vo, but the Swiss phar­ma could find a sig­nif­i­cant niche treat­ing these ear­ly tu­mors.

The next such breast can­cer tri­al Cowen ex­pects to reach pri­ma­ry com­ple­tion is IM­pas­sion050, for neoad­ju­vant and ad­ju­vant HER2-pos­i­tive breast can­cer. The com­pa­ny is al­so run­ning a col­orec­tal ad­ju­vant tri­al due to read out soon. A re­nal ad­ju­vant tri­al may not fin­ish un­til 2022 but is pro­ject­ed to be the first check­point study to read out in that set­ting.

They’ll be far from alone, though. Along with Roche, As­traZeneca, Bris­tol My­ers, and Eli Lil­ly may all put out da­ta lat­er this year in ad­ju­vant or neoad­ju­vant lung can­cer. Mer­ck, tra­di­tion­al­ly the leader in the check­point field with Keytru­da, has sev­er­al tri­als set to read out in the longer term, be­tween 2022 and 2027.

Suc­cess, too, is far from a guar­an­tee. The first ad­ju­vant tri­al Cowen ex­pect­ed to read out was IMvig­or010, test­ing Tecen­triq in a form of non-metasta­t­ic blad­der can­cer. They were right. A read­out came in late Jan­u­ary. The re­sults, how­ev­er, were neg­a­tive.

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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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.

UP­DAT­ED: Gilead keeps push­ing trove of Trodelvy da­ta as it seeks to be­come new stan­dard of care in TNBC

Gilead is continuing to churn out results for its newly approved drug Trodelvy, and #ESMO21 is the latest stop on the data train.

The biopharma put out new quality of life data in second-line patients with metastatic triple-negative breast cancer, saying that a sub-analysis from their Phase III study showed significant and clinically meaningful improvements in health-related quality of life over standard of care.