Mi­nor­i­ty racial groups con­tin­ue to be dis­mal­ly rep­re­sent­ed in can­cer tri­als — study

Da­ta re­veal that dif­fer­ent racial and eth­nic groups — by na­ture and/or nur­ture — can re­spond dif­fer­ent­ly in terms of phar­ma­co­ki­net­ics, ef­fi­ca­cy, or safe­ty to ther­a­peu­tics, but this dis­par­i­ty is not nec­es­sar­i­ly ac­count­ed for in clin­i­cal tri­als. A fresh analy­sis of the last decade of US can­cer drug ap­provals sug­gests the trend con­tin­ues, ce­ment­ing pre­vi­ous re­search that sug­gests on­col­o­gy tri­als are woe­ful­ly un­der-rep­re­sen­ta­tive of the racial make­up of the re­al world.

The study, pub­lished in the jour­nal JA­MA On­col­o­gy, eval­u­at­ed 230 tri­als to see whether spon­sors re­port­ed the racial com­po­si­tion of the pa­tients en­rolled in their stud­ies, and how mi­nori­ties were rep­re­sent­ed (ver­sus their ac­tu­al pop­u­la­tion preva­lence) in clin­i­cal tri­als that led to can­cer drug ap­provals from 2008 to 2018.

Re­searchers from the Uni­ver­si­ty of British Co­lum­bia, the Uni­ver­si­ty of Texas MD An­der­son Can­cer Cen­ter, the Fred Hutchin­son Can­cer Cen­ter in Seat­tle and Bay­lor Uni­ver­si­ty found that 145 (63%) dis­closed at least one race — but a mea­ger 18 (7.8%) doc­u­ment­ed the four ma­jor races: White, Asian, Black and His­pan­ic.

Com­pared to the ac­tu­al make­up of US can­cer pa­tients — Blacks (22% of ex­pect­ed) and His­pan­ics (44% of ex­pect­ed) were un­der­rep­re­sent­ed com­pared with Whites (98% of ex­pect­ed) and Asians (438% of ex­pect­ed), the analy­sis found.

This pat­tern is con­sis­tent — even though the NIH re­quires that mi­nor­i­ty pop­u­la­tions be ap­pro­pri­ate­ly rep­re­sent­ed in clin­i­cal re­search. Cor­po­ra­tions, which car­ry the li­on’s share of drugs across the fin­ish line, are on­ly rec­om­mend­ed to shore up rep­re­sen­ta­tion by the FDA.

A study ex­plor­ing the rea­sons be­hind chron­ic un­der­rep­re­sen­ta­tion of mi­nori­ties in on­col­o­gy tri­als, pub­lished in 2016, cit­ed a sys­tem­at­ic re­view of late-stage can­cer tri­als from 1990 to 2000 and 2001 to 2010 showed that eth­nic mi­nori­ties, par­tic­u­lar­ly African-Amer­i­cans, were not ad­e­quate­ly rep­re­sent­ed.

In stud­ies con­duct­ed be­tween 2001 and 2010 that re­port­ed race/eth­nic­i­ty, re­view­ers found that 82.9% of par­tic­i­pants were White, 6.2% were African Amer­i­can, 3.3% were Asian, 2.2% were His­pan­ic, and 0.1% were Na­tive Amer­i­can. In tri­als con­duct­ed be­tween 1990 and 2000, 89% of par­tic­i­pants were White, 10.5% were African Amer­i­can, 0.4% were His­pan­ic, and 0.04% were Asian. Even though the pro­por­tion of White par­tic­i­pants de­creased across the two pe­ri­ods, Whites con­tin­ued to com­prise a large ma­jor­i­ty of par­tic­i­pants, and the pro­por­tion of African Amer­i­can par­tic­i­pants de­creased be­tween the pe­ri­ods 1990 to 2000 and 2001 to 2010, the re­searchers ex­trap­o­lat­ed. Low mi­nor­i­ty rep­re­sen­ta­tion re­sults from “pre­ventable and in­ter­linked poli­cies, prac­tices, and bar­ri­ers at the sys­tem, in­di­vid­ual, and in­ter­per­son­al lev­els,” they con­clud­ed.

The pat­tern of dis­pro­por­tion­ate en­roll­ment in tri­als test­ing treat­ments for can­cer — a dis­ease which there are pro­nounced racial and eth­nic dis­par­i­ties in in­ci­dence and mor­tal­i­ty — is es­pe­cial­ly con­cern­ing giv­en the new wave of check­point in­hibitors.

In a sep­a­rate study pub­lished this May, re­searchers found that Black pa­tients con­sti­tut­ed less than 4% of pa­tients re­cruit­ed across mul­ti­ple tri­als that sup­port­ed the ap­proval of im­mune check­point in­hibitors for lung can­cer. The dis­crep­an­cy was echoed in tri­als con­duct­ed in re­nal cell car­ci­no­ma and oth­er tu­mor types.

“The in­ad­e­quate rep­re­sen­ta­tion of mi­nor­i­ty pa­tients on im­munother­a­py clin­i­cal tri­als could per­pet­u­ate out­come dis­par­i­ty be­cause the unique bi­ol­o­gy of the host and the tu­mors from this sub­pop­u­la­tion is not ac­count­ed for as new treat­ment al­go­rithms to guide op­ti­mal use of im­munother­a­py are de­vel­oped for use in the re­al world,” the re­searchers sug­gest­ed.

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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Lat­est news: It’s a no on uni­ver­sal boost­ers; Pa­tient death stuns gene ther­a­py field; In­side Tril­li­um’s $2.3B turn­around; and more

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President Biden and Pfizer CEO Albert Bourla (Patrick Semansky/AP Images)

Chaot­ic ad­comm sees Pfiz­er/BioN­Tech boost­ers re­ject­ed for gen­er­al pop­u­la­tion, but rec­om­mend­ed for old­er and high-risk pop­u­la­tions

With just days before President Joe Biden’s Covid-19 booster rollout is set to go into effect, an FDA advisory committee appeared on the verge of not recommending boosters for anyone in the US before a last-minute change of wording laid the groundwork for older adults to have access to a third dose.

The FDA’s adcomm on Vaccines and Related Biological Products (VRBPAC) roundly rejected Pfizer/BioNTech booster shots for all individuals older than 16 by a 16-2 vote Friday afternoon. Soon after, however, the agency posed committee members a new question limiting booster use to the 65-and-older population and individuals at high risk of disease due to occupational exposure or comorbidities.

As­traZeneca, Dai­ichi Sanky­o's ADC En­her­tu blows away Roche's Kad­cy­la in sec­ond-line ad­vanced breast can­cer

AstraZeneca and Japanese drugmaker Daiichi Sankyo think they’ve struck gold with their next-gen ADC drug Enhertu, which has shown some striking data in late-stage breast cancer trials and early solid tumor tests. Getting into earlier patients is now the goal, starting with Enhertu’s complete walkover of a Roche drug in second-line breast cancer revealed Saturday.

Enhertu cut the risk of disease progression or death by a whopping 72% (p=<0.0001) compared with Roche’s ADC Kadcyla in second-line unresectable and/or metastatic HER2-positive breast cancer patients who had previously undergone treatment with a Herceptin-chemo combo, according to interim data from the Phase III DESTINY-Breast03 head-to-head study presented at this weekend’s #ESMO21.

Merck Research Laboratories CMO Roy Baynes

Mer­ck­'s Keytru­da un­corks full da­ta on lat­est ad­ju­vant win — this time in melanoma — adding bricks to ear­ly can­cer wall

In recent months, the battle for PD-(L)1 dominance has spilled over into early cancer with Merck’s Keytruda and Bristol Myers Squibb’s Opdivo all alone on the front lines. Keytruda now has another shell in its bandolier, and it could spell a quick approval.

Keytruda cut the risk of relapse or death by 35% over placebo (p=0.00658) in high-risk, stage 2 melanoma patients who had previously undergone surgery to remove their tumors, according to full data from the Phase III KEYNOTE-716 presented Saturday at #ESMO21.

Mer­ck flesh­es out Keytru­da win in first-line cer­vi­cal can­cer, adding more fire­pow­er to its ear­ly can­cer push

Merck has worked hard to bring its I/O blockbuster Keytruda into earlier and earlier lines of therapy, and now the wonder drug appears poised to make a quick entry into early advanced cervical cancer.

A combination of Keytruda and chemotherapy with or without Roche’s Avastin cut the risk of death by 33% over chemo with or without Avastin (p=<0.001) in first-line patients with persistent, recurrent or metastatic cervical cancer, according to full data from the Phase III KEYNOTE-826 study presented Saturday at #ESMO21.

EQRx chairman Alexis Borisy and CEO Melanie Nallichieri

EQRx, CStone un­furl full lung can­cer da­ta for PD-L1 drug in what the part­ners are call­ing a first

As a self-stylized drug pricing disruptor, EQRx has high hopes for its lead PD-(L)1 to offer proof of concept for the entire business model. After touting a win back in May, the biotech is back with full data in lung cancer that could back up an approval.

Patients dosed with EQRx and CStone Pharmaceuticals’ sugemalimab posted median progression-free survival of 9 months compared with 5.8 months for patients given placebo (p=0.0026), according to full data from the Phase III GEMSTONE-301 study in Stage III non-small cell lung cancer set to be presented at this weekend’s #ESMO21.

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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 Innate’s 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.