Oncology

Treatment options and survival rates for patients with the world’s deadliest cancers have skyrocketed over the course of decades with much credit to the pharma and biotech industry. But how do drugmakers reach the critical next step in innovation?

That’s not a question easily answered by even the top oncology companies as they seek opportunities for game-changing treatments in a sea of incremental efforts. Although arguments can be made that “me-too drugs” offer benefits for patients, pharma giants need to stand out with new modalities or breakthroughs to make a difference, said Mark Wildgust, vice president of oncology global medical affairs at Johnson & Johnson Innovative Medicine.

Wilgust pointed to immunotherapy as an area with untapped potential following the previous decade’s outpouring of checkpoint inhibitors. While PD-1s like Merck & Co.’s Keytruda and Bristol Myers Squibb’s Opdivo, for example, are still amassing new indications and market growth, there’s room for new molecules that address unmet medical need, he said.

“How do you innovate where innovation didn’t exist before? And how do you innovate on top of innovation?” Wildgust asked during the annual meeting of the American Society of Clinical Oncologists this year. “When you look today at oncology as a whole, immunotherapy is at the forefront of where we’re going to change cancer therapy from incremental change to fundamental change.”

For J&J and others in oncology, eradicating cancer — once a pie-in-the-sky ambition — is now a more realistic possibility. But for a therapeutic area with so many distinct diseases, that effort will require new approaches and a wide range of scientific expertise.

“I have to be super careful when I say this, but we are taking steps closer to a progression-free cure every day,” Wildgust said. “How do you make [immunotherapies] better? You learn and understand the biology, and you innovate beyond that.”

Pushing for cures that ‘sound like science fiction’

Immunotherapies for oncology come in many forms, all designed to make cancer cells more vulnerable to a patient’s immune system. And as immunotherapeutic approaches like cell therapy mature, they’re generating enthusiasm in long-running studies that showcase their durability over time.

J&J’s Carvykti, a CAR-T cell therapy with a single infusion, achieved a “transformative” five-year trajectory in patients with returning multiple myeloma, Wildgust pointed out. A third of patients in the follow-up trial did not see their disease progress during those five years — historically, patients experience less than six months of progression-free survival and overall survival of only about one year.

That kind of advance deserves to be shouted from the rooftops, Wildgust said, so oncologists and patients can benefit.

“We need to help communicate that information so that community oncologists go, ‘Wow, it’s changing the outcome,’” Wildgust said. “It’s a combination of unlocking the barriers to get our medicines used where the patients are and cutting through the chatter to share that science in an unequivocal way.”

At a company like J&J, which has several hundred irons in the fire, there are always more drugs on the horizon to push the boundaries of cancer treatments. 

While Carvykti is considered one of the best in its class of multiple myeloma treatments, it wasn’t the first to market — Bristol Myers’ Abecma holds that title. But J&J is gunning to be first in other areas with early-stage prospects.

At ASCO, the pharma giant presented first-in-human data in prostate cancer with a bispecific antibody called pasritamig targeting a new antigen called KLK2 combined with a CD3-targeting antibody.

“This is one of the safest bispecifics we have ever seen,” Wildgust said. “What we want to do is to develop medicines that give patients more time and more hope — and part of that is looking to not just incrementally change outcomes, but to get in front of cancer and change the biology.”

With each new advance in these various modalities, ultimately the goal of J&J’s pipeline is to eradicate cancer in its entirety. What does that look like?

“It sounds like science fiction, but it’s becoming reality where we can treat patients, and intercept and stop patients from ever having the disease,” Wildgust said. “It’s a new way of thinking.”

Collaborations that create ‘modalities of the future’

Japan’s Astellas Pharma is thinking well into the future of drug development for oncology, and chief commercial and medical affairs officer Claus Zieler wants to make sure the company isn’t just focusing on today’s innovations but preparing for the next ones.

“We believe you need to create a portfolio where you have different shots on goal,” Zieler said. “Maybe not all will be successful, but you’re increasing your chances of bringing an innovation to treat patients in a better way in the future.”

While Astellas has oncology treatments like the monoclonal antibody Vyloy for gastric cancer — and potentially pancreatic cancer down the road — the company has also focused on external business development and collaborations to explore the outer reaches of cancer innovation.

Earlier this year, Astellas showcased long-term results from a study of Padcev, an ADC developed with Seagen, now owned by Pfizer. The drug is approved in the U.S. and other markets in combination with Merck’s immunotherapy powerhouse Keytruda for patients with urothelial cancer, and the study demonstrated doubled overall survival and progression-free survival compared to chemotherapy.

These collaborations are a must for oncology advances, Zieler said.

“If you look at innovation in this industry, it is not very centralized — it is not the big players that have all the innovations,” Zieler said. “Because of that decentralized nature, you are almost forced to build partnerships … as a very efficient way of bringing together skill sets in a complex industry.”

Just ahead of this year’s ASCO meeting, Astellas announced it purchased exclusive rights to a new ADC from Evopoint Biosciences targeting a biomarker found in gastric, gastroesophageal and pancreatic cancers.

“We’re partnering a skill set in clinical development with research and innovation in antibody-drug combination technology,” Zieler said. “If you didn’t bring together players who dominate those skills, you would either have a much longer development time — or you would maybe never even get there.”

Zieler sees the same potential in gene and cell therapy as some of Astellas’ future shots on goal, along with expanding its expertise in ADCs.

“It’s a hugely exciting time for us as a company to, on one hand, grow in the market and, on the other hand, build a portfolio of technologies for the future,” Zieler said. “In 10 years, even 20 years, we want to be at a point where we say, ‘OK, we are one of the companies at that forefront, because we built up our know-how.”

Antibody-drug conjugates were the topic du jour at this year’s annual meeting of the American Society of Clinical Oncology, and the rising trend in cancer care has many in the industry champing at the bit for a piece of the action.

It wasn’t always a sure bet that ADCs would break through the noise, though. The first one approved by the FDA — Mylotarg from Pfizer subsidiary Wyeth for acute leukemia — came to market in 2000. The company voluntarily withdrew the treatment 10 years later due to high liver toxicity, but the concept was strong. 

A cancer-killing drug with an antibody homing device attached has the potential to target specific tumors and keep dosing to a healthier minimum. 

“It’s essentially smart chemo,” said Ethan Smith, therapy area director for oncology at Norstella.

Despite a rough start, researchers have been tearing down the walls in subsequent generations of ADCs. Now, 15 different molecules have been approved by the FDA. The latest, Emrelis from AbbVie, represents a distinct approach to non-small cell lung cancer by targeting the biomarker c-Met.

The scientific and market success of flagship ADCs like Daiichi Sankyo and AstraZeneca’s groundbreaking breast, gastric and lung cancer drug Enhertu is paving the way for the modality to move into earlier lines of therapy for patients, as well as the next generation of targeted cancer medicines.

Being the ‘flag carrier’

While drugmakers have overcome some of the early safety challenges of ADCs, getting the formula to the right balance of cancer-killing effectiveness without dangerous side effects is still tricky.

“One of the biggest challenges of ADCs that hasn’t really gone away is engineering them — you’ve got your [monoclonal antibody], your linker and your payload, and making sure they all work in tandem has been difficult,” Smith said. “It’s only been around the last five years where many of these challenges have been resolved.”

Getting the drug-to-antibody ratio correct and a stabilized linker to deliver a potent payload without too many off-target effects has been the goal for drug developers. And the established target of HER2, present in about one in five instances of breast cancer, helped make Enhertu an important entry, Smith said.

“For most analysts, Enhertu has the highest forecasted revenues and is the one breaking a lot of ground, particularly across breast cancer in nearly every setting,” Smith said. “It is a flag carrier of ADCs.”

One of the compelling aspects of ADCs is you can rechallenge a target, Smith said. For example, a patient taking Roche’s monoclonal antibody Herceptin for a HER2-positive tumor can follow up with Enhertu afterward without encountering resistance to the target — only resistance to the payload, which is another hurdle moving forward.

Enhertu is also proving its worth in earlier stages of care. At ASCO, one of the most talked-about studies was a late-stage trial in which the treatment outperformed chemotherapy as a first-line drug.

Smith called it potentially “practice changing.”

Daiichi Sankyo is now seeking approvals in these earlier-disease positions, Ken Keller, head of the company’s global oncology business unit, said during a PharmaVoice and BioPharma Dive event yesterday.

“As successful as Enhertu has been so far, the story is still evolving,” Keller said. “Most of our indications early on were in late-stage disease patients who had failed many lines of therapy — we’re at the point in its life now where we have top-line readouts for a number of different studies that are moving Enhertu earlier and earlier in the treatment paradigm.”

And like many roads in oncology, Enhertu’s leads to tie-ups with other successful cancer treatments to squeeze as much utility out of the molecule as possible.

“As we move earlier, almost all of our trials will be in combination with different [immuno-oncology] drugs and … even chemotherapy drugs,” Keller said. “As you move forward, the opportunity to leverage different [mechanisms of action], especially ADCs and IO therapies, that’s going to deliver the best outcomes for patients.”

Pfizer rising

This year’s ASCO meeting has had the biggest ADC showing to date, which has been growing year by year, Smith said.

“Back when ADCs first came into play, that was before we had a lot of the validated targets we have today,” Smith said. “HER2 has been around for a long time and remains an established target, but now we’re seeing much bigger development in the payloads themselves for a next generation of ADCs.”

For example, Pfizer, which acquired early ADC innovator Seagen in 2023, is going after a familiar target in the oncology arena: the PD-(L)1 pathway. Checkpoint inhibitors like Merck & Co.’s Keytruda and Bristol Myers Squibb’s Opdivo, among many others, have blocked the pathway in an immuno-oncology setting, and Pfizer is betting the same tracking mechanism can help an ADC shine.

Pfizer has also teamed up with biotech Summit Therapeutics to combine ADCs with bispecific antibodies in early-stage development.

“There’s not much detail on it, but if that’s something that’s successful, they could be riding not just an ADC wave but the PD-(L)1 and VEGF wave with Summit,” Smith said. “That’s something to look out for.”

Gilead’s Trodelvy also turned heads at ASCO with a study in first-line triple-negative breast cancer along with Keytruda. Providing a chemo-free treatment as a first option for patients would address a highly unmet-need population, Smith said.

Leading a trend

Being an early adopter of an oncology trend like ADCs isn’t always an easy feat to pull off for drugmakers. While data is king, getting a foot in the door requires a first step into the unknown, Smith said.

“The proof in these trends is always the data, but companies can’t wait that long — the later someone is to a licensing deal, the more they have to pay,” Smith said. “In truth, a lot of these licensing deals happen on faith, and perhaps some desperation.”

And the industry doesn’t always move on the right trends. A rush on Lag3 blockades, for instance, brought on the approval of Bristol Myers Squibb’s melanoma drug Opdualag in 2022, but a series of trial failures and axed programs from pharma giants like Merck and Roche left a sour taste.

Even though it takes faith to enter the arena, data will still always be the true test of a modality’s lasting power, Smith said.

“A trend is only confirmed when you’ve got that threshold of data — even if you see a bunch of companies licensing a new technology, that doesn’t validate it,” Smith said. “Perhaps it’s just pessimism, but until you have that validated data, it’s best to stay away from the noise of licensing activity.”

ADCs are beginning to cross that threshold, he said. Between established leaders and a slate of novel targets on the way, some hurdles remain, but the trend is shaping up to be a game changer.

Sponsored content

By Quest Diagnostics

Patient data fuels every stage of a drug’s development and commercialization. But pharma companies bringing different drugs to market at different times typically must purchase real-world data from different vendors, case by case. The process is costly, inefficient, and time-consuming. What’s more, since usage parameters are spelled out in contracts, data likely can’t be shared with other internal teams, even those working in the same therapeutic area (TA).

In response, Quest Diagnostics has recently developed a suite of therapeutic area datasets that can be used across teams for a variety of use cases. Curated by medical, clinical, and biostatistical experts, the datasets include those biomarkers relevant to disease discovery, diagnosis, and monitoring.

Simplifying Licensing

As noted above, teams typically access lab data for a single use case. Each additional use case triggers a change order and introduces delays, since new contracts must be reviewed and approved.

“We’ve taken a different approach by offering simple enterprise licensing pricing based on field of use, whether clinical or commercial,” says Parag More, executive director, healthcare analytics solutions (clinical trials) at Quest Diagnostics. “Enterprise contracts cover a very broad set of use cases for an indication.”

More notes that companies can attain both cost savings and operational efficiencies through enterprise pricing. In fact, Quest’s internal cost calculations show that companies could save up to 40% off their yearly data costs.

A Look at Quest’s TA Datasets

Quest’s TA datasets offer curated, indication-specific sets of clinical and genetic data for more than 50 diseases. All data goes through a tokenization process, so it never shows who the individual patients are.

The data is drawn from Quest’s large and growing database, which includes results from more than 378 million unique patients and from 3,500-plus tests. It can also be overlapped with data from other sources, including claims, electronic health records, and prescription data, which enables a more robust patient profile.

“The richer the data pharma companies can access, the more useful it can be,” More says. “Researchers and marketers alike benefit when datasets include clinical biomarkers, genetic biomarkers, and diagnostic codes; a combination of these can help paint a more accurate picture.”

In oncology alone, Quest’s TA datasets cover more than three dozen diseases, including breast cancer, colorectal cancer, prostate cancer, and more. Other diseases include Alzheimer’s disease, asthma, ulcerative colitis, and more.

Prostate cancer is a good example of what the TA datasets contain. Most people are familiar with the prostate-specific antigen (PSA) test, which is used both to screen men for prostate cancer and to monitor disease progression. But the PSA test is just one of more than 40 tests Quest Diagnostics administers that can give insights into prostate cancer, a disease that affects 1 in 8 men during their lifetime. For example, elevated levels of alkaline phosphate (ALP) in the blood have been associated with an increased risk of mortality in patients with hormone-sensitive prostate cancer.

“These tests are included in our prostate cancer TA dataset, as are 15-plus genetic markers and two diagnostic and ICD-10 codes,” More says. “That gives pharma companies a far more robust picture of this common disease than PSA results alone.”

The inclusion of genetic markers is especially valuable for a disease such as prostate cancer, which is a rich target for gene therapy. In fact, more than 150 ongoing clinical trials involve gene therapies to treat prostate cancer (along with more than 1,000 involving cell therapies).

Quest transforms complex genetic information into simplified categorical values. This discretization makes analysis easier.

Use Cases for Lab Data

Quest’s TA datasets can support a wide range of clinical and commercial use cases. Here are a few ways pharma companies can use the data under enterprise licensing:

• Clinical trial feasibility and recruitment
• Patient journey studies
• Identification of potential prescribing physicians
• Tailoring product launch strategies
• Health economics and outcomes research

Companies that license Quest’s TA datasets can access two distinct cohorts, depending on their needs:

• Test-Based Cohort: Focuses on indication-specific diagnostic tests over the last five years, plus a one-year prospective; this dataset is ideal for researchers seeking to study critical biomarkers and treatment responses linked to specific tests.
• Patient-Centric Cohort: Includes all lab encounters for patients who meet the criteria for specific therapeutic areas, offering a complete longitudinal record over the last five years, plus a one-year prospective. This deidentified dataset allows for a comprehensive analysis of patient journeys, outcomes, and the identification of comorbidities.

“We’re excited to offer these curated datasets to pharma companies,” More says. “We’re confident that they can help those companies drive efficiency and maximize their data usage.”

To learn more about their comprehensive therapeutic area datasets, visit Quest Diagnostics.

Disclaimer: The use of genetic data varies on a case-by-case basis and is subject to state-level regulations.

For decades, researchers have worked to create drugs that teach the immune system to kill cancer cells the way traditional vaccines attack viruses. But while cancer vaccines have shown flashes of promise and a few have made it to market, it’s been a long and bumpy road, according to James Drew, director of content strategy for Citeline, in an email.

“The first therapeutic cancer vaccine approval in the U.S. was back in 2010,” he said, referring to Dendreon Pharmaceuticals’ prostate cancer treatment Provenge. “Since then, a series of late-stage trial failures by other cancer vaccine products have tempered expectations.”

But new scientific insights into tumor immunology and advances in mRNA technology are turning the tide, and oncological vaccines are finally gaining traction. 

“The number of cancer vaccines in active preclinical and clinical development has almost doubled in the past 15 years, now sitting at over 350 unique therapies globally,” Drew said. There are more than 400 ongoing trials and more than 200 in the works, according to Citeline data.

Immunotherapy evolution

Therapeutic cancer vaccines differ from more traditional vaccines such as the human papillomavirus or the hepatitis B shots that prevent cancer by mitigating related viral threats. Instead, they teach the body to recognize specific antigens only expressed by cancer cells — otherwise, cancer cells avoid detection by masking those antigens.

“Generally, tumors with high mutation rates produce a lot of these neoantigens and so have been a key area of focus for drug development,” Drew said. 

Companies like Merck & Co. and Moderna, as well as smaller biotechs, are developing options for 46 different cancers. About 20% of drugs target non-small cell lung cancer, and late-stage trials include options for melanoma, breast, pancreatic and brain cancers, according to Citeline.

While immune checkpoint inhibitors prime the immune system to fight cancer, therapeutic cancer vaccines train the body to continue recognizing cancer antigens and halt recurrence. And because of the potential symbiotic relationship between the therapies, companies are increasingly pairing vaccine technology with checkpoint inhibitors — like Merck’s Keytruda or Bristol Myers Squibb’s Opdivo, for instance — to boost efficacy. 

“[Checkpoint inhibitors] dampen the immunosuppressive tumor environment, which in theory could improve the efficacy of a cancer vaccine,” Drew said. “In this context, cancer vaccines have great potential to improve response and reduce relapse rates in patients with tumors that respond to other immunotherapies.” A recent phase 1 kidney cancer trial at Dana Farber Cancer Institute showed early promise with a personalized vaccine given to patients with late-stage renal cell carcinoma. Among the nine patients in the trial, the median cancer-free rate was 35 months.

Another small trial of a personalized mRNA vaccine saw half of the 16 participants mount a lasting immune response aimed at keeping pancreatic cancer at bay after surgery. Six of the eight responders remained cancer-free in the study period.

Early victories, new starts

The FDA has already approved two antigen-targeting cancer vaccines — Provenge, which targets metastatic prostate cancer, and Imlygic, for metastatic melanoma. Two other similar FDA-approved options that use a different mechanism are Bacillus Calmette-Guérin and Adstiladrin for bladder cancer.

And there are many more in the pipeline. Among the more promising contenders are Merck and Moderna’s mRNA-4157 now in phase 3 in combination with Keytruda for melanoma, Drew said. 

It’s also in testing for NSCLC, bladder and renal cancer. Other late-stage options include IO Biotech’s IO102-IO103 for melanoma, Polynoma’s seviprotimut-L also for melanoma, and Zeltherva from Sellas Life Sciences in phase 3 for acute myeloid leukemia.

Roadblocks ahead

Despite theoretical promise, especially when it’s personalized to the patient, can be costly, difficult and time-consuming to make. 

“Off-the shelf products use neoantigens widely expressed in certain tumor types and could have more widespread utility, but proving strong efficacy could be a challenge,” Drew said. 

But scientists have been hamstrung by an ongoing struggle to find the right antigens. 

“Ideal candidates are highly expressed only in tumor cells, invoke strong and rapid dendritic and T cell responses, and have limited off-target effects,” he said. “But finding these among the thousands of candidates is a needle-in-the-haystack exercise.” 

Companies are turning to AI to speed up the search.  

Scientists also need to overcome tumor-related hurdles, namely their ability to outwit and suppress the immune system. However, work continues, and hopes are high that investigational vaccines will one day give patients new options.

“I’d say the interest from pharma and biotech is there, and we can expect these therapies to play an increasing role in treatment regimes in the second half of this decade,” Drew said.

Natural killer cells continuously patrol the human body, swiftly eliminating viruses and cancer cells, like sharks in prey-laden waters. Several biotech companies are harnessing the power of these innate immune crusaders in oncology and autoimmune diseases, potentially positioning them as a strong competitor to CAR-T cell therapies.

Unlike CAR-T cells, NK cells don’t need genetic modification to recognize a specific threat — they act broadly without customization. However, some NK companies, such as Fate Therapeutics and Cytovia Therapeutics, enhance NK cells with chimeric antigen receptors to increase precision and efficacy.

NK cell options tend to produce fewer serious side effects, making them particularly appealing in the autoimmune space, which has less risk tolerance than oncology. 

“The advantage of NK cells over a T-cell approach is that NK cells can kill the target cell without causing that runaway cytokine release syndrome,” said Dr. Fred Aslan, president and CEO of Artiva Biotherapeutics. In addition to potential safety advantages, NK cell therapies could disrupt the market by offering a less costly off-the-shelf option that speeds patient access.

A change in direction

Artiva began testing its lead NK cell therapy, AlloNK, in cancer but shifted much of its attention to autoimmune applications following the success of a German CAR-T cell study that showed the technology’s potential to treat serious autoimmune diseases such as lupus. Aslan said NK cells could have similar abilities, and the appeal of a larger market and earlier-stage competition helped drive the pivot. 

Artiva has raised more than $200 million in private funding to back its efforts, in addition to a $167 million IPO in July, reflecting the rising interest in the research area. But the company faces considerable competition from companies such as Dragonfly Therapeutics, which has collaborations with Merck & Co., AbbVie, Gilead Sciences, Bristol Myers Squibb and more.

AlloNK works alongside monoclonal antibodies, such as rituximab or obinutuzumab, in combinations chosen for each target. In patients with cancer or autoimmune disease, NK cells are often diminished or impaired. 

“Although a monoclonal antibody can be effective, it may not have the opportunity to work as well because of poor NK cell function,” Aslan said. “So our basic hypothesis is that by giving large numbers of exogenous NK cells together with monoclonals, we get to the cell we want to kill, and we do it much more effectively, beyond what a monoclonal could do by itself.”

Artiva derives NK cells from umbilical cord blood.

“From one umbilical cord unit, we can make thousands of vials, each with a billion cells,” Aslan said. “Our dose today in the clinic is three billion cells per patient, so that means one umbilical cord could treat over 1,000 patients.” 

The projected cost of vial is less than $1,000, and treating a patient requires roughly three weekly outpatient infusions — ringing up a substantially lower cost compared with CAR-T, which typically costs hundreds of thousands of dollars, Aslan said. 

“Our NK cell therapy could really move the needle from a payer perspective and an access perspective,” he said.

Artiva established an early milestone in autoimmunity as the first NK cell therapy to gain IND approval. AlloNK also received FDA fast-track designation to treat lupus nephritis and relapsed/refractory non-Hodgkin lymphoma of B-cell origin. The company dosed its first lupus patient in April. 

Artiva is also testing a basket set of indications, including rheumatoid arthritis, pemphigus vulgaris and vasculitis. The company is still evaluating AlloNK’s potential in non-Hodgkin lymphoma and relapsed/refractory CD30-positive lymphomas, Aslan said.

“There will be some very compelling treatments coming out of this field and there will be room for a lot of different players here,” Aslan said.

Antibody-drug conjugates have become a “choose your own adventure” tool in pharma R&D.  

Due to their versatility, the therapies have proved themselves as a potent weapon against many oncology indications, AstraZeneca’s vice president and head of medical affairs for U.S. oncology told PharmaVoice last year. And the adventure more companies are choosing is solid tumors. 

AbbVie scored the latest breakthrough in the solid tumor arena this year when the FDA granted an accelerated approval to its ADC Emrelis. The company won the go-ahead for patients with the most prevalent type of lung cancer who have a high expression of a protein called c-Met — a population currently facing a “poor prognosis and limited treatment options,” AbbVie said in a statement.

The win for Emrelis — AbbVie’s first internally developed solid tumor drug — marked a milestone payoff for the company. After a successful run developing blood cancer drugs, AbbVie shifted its focus to solid tumors and playing catchup in the ADC space.

“AbbVie was always best known for its strong presence in hematological malignancies … and it has now become a serious contender in solid tumor oncology,” said Neha Anand, an analyst with Citeline.

Emrelis is poised to capture a population of about 60,000 patients with non-squamous non-small cell lung cancer in the U.S. and Europe as a first-in-class medication, Citeline predicts. Assuming the approval holds after AbbVie reports data from an ongoing phase 3 trial, Emrelis could become a blockbuster, Anand said, or at least pull in about $500 million per year.

And the breakthrough will give AbbVie’s ADC-focused strategy more momentum.

“This approval demonstrates the ability of this company to develop and commercialize ADCs and it provides a foundation for other ADC candidates in their pipeline,” Anand said. “It also gives a major boost to investor confidence.”

For other drugmakers, the Emrelis milestone showcases how pharma can have a winning strategy targeting solid tumors with ADCs.

How to succeed in ADCs

With the Emrelis nod, drug developers have notched nearly half a dozen approvals for ADCs in solid tumor indications and over 100 candidates are in clinical development.

“The ADC market for solid tumors is rapidly evolving and experiencing significant growth,” Anand said.

Major deals in recent years demonstrate the industry’s eagerness to jump into the ADC ring.

Pfizer’s $43 billion acquisition of ADC specialist Seagen in 2023 offered a significant boost to the pharma’s oncology pipeline, particularly in solid tumors.

Genmab also made a play in the space when it picked up ProfoundBio for $1.8 billion last year to acquire a portfolio of next-generation ADCs, including solid tumor candidates. 

And several companies are poised to showcase milestone clinical data. 

Daiichi Sankyo and AstraZeneca will present phase 3 clinical results at the upcoming American Society of Clinical Oncology conference for their blockbuster ADC Enhertu that could further expand its reach. The drug has already been OK’d for several cancer indications, and became the first tumor-agnostic HER2-directed therapy approved by the FDA last year. The new late-stage results could support approval for Enhertu as a first-line treatment in HER2-positive breast cancer, offering another opportunity for growth.

While these developments breathe more life into the market, there are caveats to making an ADC strategy work. 

Regulatory agencies have demonstrated their support for ADCs that target unmet needs in solid tumors but have also set a high bar for efficacy standards, Anand said.

Because many ADCs carry off-target toxicities, new candidates must be more effective than market competitors to provide an acceptable risk-benefit ratio. In addition to requiring “mature data,” regulators want strong results for overall and progression-free survival, specifically in later line settings, Anand said.

By focusing on patients with a high expression of the c-Met protein, AbbVie also showcased another valuable R&D strategy: targeting specific biomarkers. But pharma companies then need to offer a validated approach to identifying the right patients.

“Regulatory agencies would prefer that companies have companion diagnostics for drugs like Emrelis that have a biomarker differentiated approval,” Anand said. 

As the field moves forward, pharma is also aiming to overcome the ongoing limitations of ADCs.

ADC hurdles

It hasn’t been all smooth sailing for drugmakers trying their hand at solid tumors with ADCs.

Pfizer scrapped development of an ADC candidate for advanced solid tumors in several cancer types earlier this year, creating a $1 billion impairment charge. The large pharma picked up the treatment in its Seagen acquisition and had once pegged it as a potential blockbuster. But “emerging competition” ultimately sank the drug along with another ADC in Pfizer’s pipeline.

ADC Therapeutics also nixed its leading asset for solid tumors late last year after positive signs in early development gave way to a low risk-benefit profile in a dose-escalation study. 

Other ADCs in development that trigger toxicities and don’t achieve superior efficacy to approved treatments could meet a similar fate, Anand said.

“You have to balance the risk-benefit profile,” she said. “Physicians look at the quality of life for patients who might already be frail from having gone through chemotherapy … [and] they prefer the drugs that have a better safety profile.” 

In general, drugmakers are now working to develop novel formulations for some of the key ADC components — the antibody agent, cytotoxic payload and chemical linker — to create therapies that are more durable and have fewer side effects. The industry is also up against ongoing manufacturing complexity for ADCs and a drug development landscape that’s increasingly competitive.

For companies that overcome those challenges, expanding into new indications then becomes key to gaining long-term traction.   

“Enhertu’s success, for example, depended on its ability to expand from its initial target and demonstrate efficacy for multiple tumor types,” Anand said. “That’s why it became so successful.”

Recurrent and metastatic cancers remain formidable challenges. But a recent radiopharmaceutical revival after years of stagnation could bring new options to the table. And If the drugs deliver on promises to expand into new types of cancer, they’ll unlock a vast market.

Radiopharmaceuticals have been in use since the 1951 approval of radioactive iodine for thyroid conditions. However, safety issues — due to broad toxicity that can harm healthy tissues along with cancerous cells — have limited their applicability. 

Now, technological advances have led to new radiopharmaceuticals that target specific receptors and deliver a precision blast of radiation to tumors while minimizing off-target effects. These developments have reignited interest in the field, driving a spate of acquisitions, including Bristol Myers Squibb’s $4.1 billion RayzeBio acquisition and Eli Lilly’s $1.4 billion purchase of Point Biopharma.

A reviving class

The radiopharmaceutical market is still nascent, said Thijs Spoor, CEO of Perspective Therapeutics, which is testing an alpha-emitting isotope, Pb-212, to target cancer cells with radiation more precisely by using peptides. 

Outside of smaller companies like Perspective, pharma giants have brought several products through the regulatory gauntlet, including Bayer’s Xofigo for prostate cancer, Novartis’s potential blockbuster Pluvicto for prostate cancer, and the neuroendocrine tumor treatment Lutathera, also from Novartis. 

But much of the field’s promise is untapped. 

“I've heard various Big Pharma players say they believe only 7% of all tumors that could be addressed with radiopharmaceuticals are being addressed,” Spoor said. “So there’s an awful lot of opportunity.” ]

Oncology targets could include head, neck, gynecologic, genitourinary, gastrointestinal and lung cancers. 

“There are all kinds of applications,” Spoor said. “We haven’t even scratched the surface of what the radiopharmaceuticals can do.”

These treatments are uniquely suited to metastatic disease, but they’re not limited just to cancer that has spread and could fill a void in the oncology market for patients who don’t respond to other options. 

Around a dozen startups are working in the space, including Ratio Therapeutics, Radiopharm Theranostics and Aktis Oncology, and are developing treatments for various cancers. 

Perspective’s formula uses a radioactive imaging agent to detect a target peptide that then drives the attack on the tumor and cancer cells that have spread. 

“With the radiopharmaceuticals, all we have to do is bind to the cell, and then we just blow it up like a mine on the ship,” Spoor said.

An early-stage trial of Perspective’s radiotherapy VMT-a-NET for neuroendocrine tumors showed that the treatment was safe and kept eight of nine patients stable. Six of the nine patients saw their tumors shrink, but only one had a confirmed response. 

The trial drew some fire because it fell short of an earlier investigator-led study, raising questions about its approach and causing a drop in the company’s stock price last fall. However, the results allowed the company to move forward with dose escalation. 

Perspective is also advancing a phase 1/2a treatment for melanoma, which recently gained FDA fast track designation, along with several preclinical programs.

Radiopharmaceuticals still have to meet critical milestones to become primary players in the oncology landscape. One of the most pressing issues for drug developers is building the necessary infrastructure. Many recent market acquisitions have aimed to give these drugs the scaffolding they’ll need to climb into the mainstream, Spoor said. 

“There are a lot of people in the space trying to create isotope supply, trying to create manufacturing capacity,” he said. 

Once these foundational elements are in place, the next challenge will be identifying the most promising candidates. 

“Everyone's looking for a pipeline — they’re looking for drugs with IP they can run with,” Spoor said. 

At a company the size of Johnson & Johnson, it would be easy for departments to become siloed, accomplishing only their own objectives without a vision of the bigger picture. But even in the earliest stages of science, units as fundamentally divided as clinical research and commercial strategy work together to achieve the pharma giant’s common goal.

As J&J pursues clinical results, Dr. Craig Tendler, vice president of late-stage development, diagnostics and global medical affairs in oncology, has to consider not only what’s happening in a non-small cell lung cancer trial but what the commercial landscape will look like so patients can ultimately benefit.

“The way I look at the commercial contribution before we even get on the market is trying to define those key attributes that are important to physicians and patients and being able to integrate that into a development program where the results will hopefully support that profile,” Tendler said. 

So he teams up early with Biljana Naumovic, J&J’s president of U.S. solid tumor oncology, to ensure everyone is on the same page. Along with the research teams, Naumovic aims to define those key attributes at the outset.

“The primary end goal is to transform the lives of patients by changing the standard of care and supporting a long, fruitful quality of life,” Naumovic said. “We’re part of this discussion at the very beginning, so that before we go into the clinic, we’re defining where we want to go — for the past 20 years, we have done just that with very informed, passionate debates.”

If a program looks like it’s not going to change the standard of care, “we stop things that we do not think are going to hit the mark,” Naumovic said.

‘A huge responsibility’

When the baton makes its way from the clinical research teams to the commercial department, everyone needs to be on the same wavelength, Naumovic said.

“Bringing really strong data to then manage patients better is a huge responsibility,” Naumovic said, referring to the August FDA approval that stemmed from overall survival data in a late-stage study for EGFR-mutated non-small cell lung cancer with the drug combo of Rybrevant and Lazcluze compared with AstraZeneca’s Tagrisso, the current standard of care.

On the research side, patients stayed on the Rybrevant and Lazcluze combination treatment longer than with Tagrisso, Tendler said, noting that the combo provided better disease control, which is a selling point down the road. And that arises from early representation of the commercial perspective in clinical program design, he said.

“The beauty of having the commercial representation is that we have better insight as to what attributes should be integrated into the comprehensive development program,” Tendler said. “This idea that we have to look to not just bring a regimen that has enhanced progression-free survival but the factor that will convince physicians to use it in a higher proportion of patients is the survival data.”

At a conference with clinical experts like this past weekend’s annual conference of the European Society for Medical Oncology, Naumovic’s job is to distill the next steps into a commercial plan.

“Once the data is out, the oncology community has a million ideas for where to take it next,” Naumovic said. “And so we can create that together.”

In bladder cancer, for instance, J&J reported mid-stage data for a device called TAR-200 designed to sit in the bladder and release chemotherapy from within, showing a response rate of more than 83%.

“It’s a very clear example of an innovation being able to deliver an older drug in a new delivery device and having it get much more effective levels throughout the treatment cycle,” Tendler said.

Results like that give Naumovic some buzz to work with when the commercial strategy comes into play.

“This has never been seen before in localized bladder cancer, and to get there with a beautifully engineered device that stays in the bladder will be a radical change to what bladder cancer looks like once we bring it to the U.S. market in the beginning of next year,” Naumovic said.

The commercial influence

While science can only be done at its own pace, commercial demand can sometimes influence the direction in which a research team takes aim. A rise in colorectal cancer among young patients has troubled oncologists and caused companies like J&J to investigate new treatment options.

In a phase 1b/2 study for patients with metastatic colorectal cancer, a combination of Rybrevant and chemotherapy resulted in an almost 50% overall response rate.

“There has been no innovation in colorectal since [Eli Lilly’s Erbitux], and we’re talking several decades,” Naumovic said. “So like we did in bladder cancer and lung cancer, we’re coming to colorectal cancer the same way — there certainly is a resurgence of higher incidence in a younger population across the developed world because of diet, and we want to make sure we’re embracing that opportunity with the results that we have.”

Overall, J&J’s clinical and commercial teams have the same endpoints in mind — finding the right approaches to move the oncology field forward while keeping today’s patients at the center of the equation.

“We are a company that aims to put chemotherapy into the history museums where it belongs and focus on targeted therapies that will allow patients to live a longer and better life,” Naumovic said. “That’s where we think the field of oncology is going.”