ASCO 2024: The latest advances in oncology clinical trials

This month kicked off with one of the leading cancer summits in the U.S., where experts gather to present novel, promising cancer research at the American Society of Clinical Oncology (ASCO) in Chicago. Biotechs from all over the country as well as other parts of the world showcased recent pipeline advancements in oncology clinical trials at ASCO 2024.

“The theme of this year’s ASCO was ‘The Art and Science of Cancer Care: From comfort to cure’ – and that really resonated as for certain cancers, the data is now so good that it is becoming a chronic disease,” said Ketan Patel, vice president of Product Management, Life Science and Healthcare at British-American analytics company Clarivate.

“This has shifted focus away from finding the best pathways and targets for certain cancers, and now optimizing the best therapeutic doses, regimens, and combinations to really impact cancer patients with a good quality of life during and after treatment.” 

Pharma giants present promising clinical data at ASCO 2024

Pharma giants like AbbVie have hopped on the trend to shift primary cancer care from chemotherapy to novel targeted therapies. At ASCO 2024, AbbVie’s antibody drug conjugate (ADC) platform was revealed, as the drugs are being developed to target solid tumors. A few years ago, ADCs had their sights on blood cancers, but now this class of drugs is used to treat various tumor types.

AbbVie’s ADCs ABBV-400 and ABBV-706 showed promising results based on early clinical data. Both the candidates designed to induce cell death by interrupting DNA replication, boosted antitumor activity in patients.

Another ADC in the limelight was British multinational AstraZeneca and Japanese multinational Daiichi Sankyo’s Enhertu. The oncology drug reduced the risk of breast cancer progression by 37% in a clinical trial against chemotherapy in patients who are HER2-positive, HER2-low, and HER2-ultralow.

This wasn’t AstraZeneca’s only triumph at ASCO this year. One of the biggest reveals at the event was ​​Tagrisso’s success in a phase 3 lung cancer trial. ​​The kinase inhibitor cut the risk of disease progression by 84% compared to placebo.

Another pharma giant’s oncology clinical trial results that charmed attendees at ASCO 2024 was Pfizer’s phase 3 study of Lorbrena, which was approved by the U.S. Food and Drug Administration (FDA) for non-small cell lung cancer (NSCLC) back in 2021. A five-year follow-up of patients with the ALK mutation revealed that Lorbrena reduced the risk of disease progression by 81% compared to Xalkori, a drug recognized as a first-line standard of care in NSCLC.

Patel found Lorbrena’s readout the most impressive at ASCO as 60% of the patients showed a five-year progression-free survival.

“This is an incredible advance for those lung cancer patients who have ALK mutations – also highlighting the impact of targeted therapy for specific mutations in cancer,” said Patel.

Big pharma KRAS inhibitors yet to meet their mark

Another class of drugs that did its round at ASCO 2024 was KRAS inhibitors. But Amgen and Bristol Myers Squibb’s (BMS’) trial results were just shy of being noteworthy. Although KRAS mutations are most common in NSCLC, BMS seems to have missed the mark with Krazati in NSCLC despite its slashing of tumor progression risk by 42%. 

The drug had a median progression-free survival (PFS) – the time during which a patient’s condition does not get worse after treatment – surpassing chemotherapy by only 1.7 months in a confirmatory study.

This is following Amgen’s failure to make the cut with its KRAS inhibitor Lumakras. It was denied full approval for NSCLC as the FDA reported that its confirmatory trial results could not be reliably interpreted. The drug had bagged accelerated approval in 2021. 

Oncology clinical trials: young biotechs present encouraging early data at ASCO 2024

Biomica’s BMC128 positive phase 1 findings bring hope to cancer patients

While ASCO 2024 was a place for pharma giants to convene, it was also a stage for young and early-stage biotechs to present their pipeline candidates that contribute to cancer research. One of which is Israel-based Biomica. Its live bacterial product (LBP) BMC128 comprising unique bacterial strains and strains present in the gut, exhibited positive preliminary results in a phase 1 clinical trial for patients with renal cell cancer (RCC), NSCLC & melanoma in combination with an immune checkpoint inhibitor.

The results presented at ASCO 2024 showed that for 64% of the patients, disease progression was paused. All the patients with RCC and 60% of patients with NSCLC demonstrated positive clinical outcomes.

“With the rising number of cancer cases worldwide, this trial’s positive phase 1 findings bring hope to patients with some of the most common malignancies that are difficult to manage as they progress,” said Elran Haber, chief executive officer (CEO) of Biomica. “While phase 1 trials generally focus on the safety of a new drug, the results of BMC128’s trial additionally indicated the efficacy of treatment, a result we were hoping to see and aim to further demonstrate in continuing trials.”

Microbiome-based therapies aim to reshape bacterial communities in the gut and restore gut health. While they address the root cause of gastrointestinal (GI) issues, they now appear to bolster patients’ response to cancer treatment.

“Emerging evidence, including these findings, increasingly indicate that harnessing intestinal bacteria could serve as a novel and effective way to complement current cancer treatments and therapies with immune-based components, providing options for cancer patients where conventional treatments fall short,” said Haber. “This is a really exciting time for microbiome-based therapies and for Biomica. We’re on the brink of a new frontier in treatment options that could transform cancer care, bringing more options and hope for patients.”

Alligator Bioscience’s mitazalimab clinical trial shows “highly encouraging” results for pancreatic cancer

Another biotech that presented promising results at ASCO 2024 was Swedish biopharma Alligator Bioscience. Its antibody mitazalimab showed an increase in median overall survival – 14.3 months – compared to chemotherapy alone in a phase 2 trial, which Soren Bregenholt, CEO of the biotech, said was “highly encouraging.”

“Pancreatic cancer has a very poor prognosis, as most patients present after metastasis has occurred, meaning treatment options are very limited,” said Bregenholt. “The unique combination of CD40 epitope specificity and Fc receptor binding provides strong effects at relevant dose levels, with a good safety and tolerability profile. This profile of mitazalimab is also what makes it possible to combine our candidate with such demanding chemotherapies as mFOLFIRINOX.”

Nanobiotix’ NBTXR3 clinical trial reveals promising data at ASCO 2024

Meanwhile, French biotech Nanobiotix, which struck a deal with pharmaceutical company Johnson and Johnson (J&J) for its lead product NBTXR3 in head and neck cancers amid money troubles last year, showcased new drug data at ASCO 2024. The drug contains electron-dense hafnium oxide nanoparticles that are administered via one-time injection and activated by radiotherapy.

NBTXR3 had a 48% overall response rate (ORR) in patients with solid tumors who hadn’t previously received treatment, and a 28% ORR in those who were treatment-resistant.

“These new results from Nanobiotix Study 1100 support the hypothesis that radiotherapy (RT)-activated NBTXR3 could potentially achieve the ‘immune priming’ effect that RT cannot achieve on its own, thereby helping to improve response rates to immune checkpoint inhibitors and/or reversing resistance,” said Laurent Levy, CEO of Nanobiotix. “If proven in later-stage clinical trials, this treatment combination could open the pathway to curative outcomes for a broader population of patients with R/M-HNSCC and beyond.”

Vaccines for cancer treatment and prevention

mRNA vaccines stand out at ASCO 2024

While a variety of oncology clinical trials were presented at the summit, one field that stood out was cancer vaccines. Moderna’s collaboration with Merck adds to the conversation. Leveraging Moderna’s mRNA technology, the two pharma giants are developing a regimen that involves the personalized therapy mRNA-4157 and Merck’s humanized antibody Keytruda for melanoma. 

“It shows the benefit in melanoma patients where almost 90% of the patients are now surviving – an incremental advance on top of existing immunotherapy – but amazing when you think about how we are chipping away at those survival odds till we get to 100% of patients who will still be alive after 4-5 years,” said Patel. “This is shifting the focus on cancer patients living longer with the disease and will also in time lead to new treatments or markets to help patients with other symptoms and dealing with cancer long-term.”

Patel believes that mRNA cancer vaccines “will keep the immune system primed to destroy any recurring cancer cells that may have survived the initial therapies,” and could prolong the survival of patients.

Off-the-shelf vaccines garner clinical recognition

Like mRNA vaccines, off-the-shelf vaccines have been garnering clinical recognition in the immunotherapy field. Massachusetts-based Elicio Therapeutics is a key contender in the space. Its lead candidate ELI-002 7P, a seven-peptide formulation of its off-the-shelf cancer vaccine, led to 71% of patients experiencing tumor biomarker reductions in a phase 1 study.

“The patients studied were at risk for poor outcomes after standard surgery and chemotherapy since they had mKRAS-driven pancreatic and colorectal cancer and had positive blood tests for circulating tumor DNA or rising tumor markers showing they had minimal residual disease,” said Christopher Haqq, chief medical officer (CMO) of Elicio Therapeutics. 

Moreover, T cell responses were observed in all the patients. Haqq believes that off-the-shelf vaccines like ELI-002 7P, which is designed to stimulate an immune response against the seven KRAS mutations present in 25% of all solid tumors, overcome the drawbacks of mRNA vaccines.

“Off-the-shelf approaches don’t have to be formulated for a particular individual and have therefore become an important part of the conversation. Elicio’s lymph node-targeting AMP platform is an example of an off-the-shelf approach that has the potential to make cancer vaccine production and administration faster and more cost-effective,” said Haqq. 

“We have also observed that personalized antigen responses join in the responses, a phenomenon called antigen spreading. In this way, lymph node-targeting amphiphiles may be able to combine the benefits of personalized and off-the-shelf approaches.”

Beyond cancer vaccines: ASCO 2024 highlights HPV prevention and weight loss drugs’ potential

But it’s not just cancer vaccines that were the talk of ASCO 2024. A study presented at the event established that the human papillomavirus (HPV) vaccine helps prevent HPV-related cancers – the most common one being cervical cancer. While it has long been known that the vaccination would protect people from HPV infections, the recent study conducted by the Thomas Jefferson University in Philadelphia confirms that cancers of the head and neck, cervix, anus, penis, vulva, and vagina, could be prevented.

Another study that caught the attention of attendees was how weight loss drugs – which have blown up in the past year – could slash the risk of cancers linked to obesity. Drugs like Ozempic and Wegovy, which are typically prescribed to treat diabetes and obesity, could lower the chances of developing 13 cancers including ovarian, liver, colorectal, pancreatic, bowel, and breast cancer, by 20%, according to the Case Western Reserve University in Ohio. Still, more research is needed to prove this.

Cancer detection tests strive for accuracy

Cancer detection tests also made a splash this year. An at-home DNA test based on saliva samples was able to detect prostate cancer that was otherwise missed in a blood test – which is often inaccurate – according to a presentation by researchers at The Institute of Cancer Research (ICR). 

Moreover, minimal residual disease (MRD) tests are becoming increasingly mainstream in cancer care. These tests are meant for patients – especially with blood cancers – who are at risk of relapsing. Cancer cells are detected through flow cytometry and polymerase chain reaction (PCR).

“These MRD tests can detect sooner whether a cancer has stopped responding to treatment or has come back after remission and allow doctors to prescribe another drug to keep the cancer at bay for longer,” said Patel.

While ASCO 2024 was an occasion where biotechs were lauded for their promising therapeutic candidates, recent flops didn’t go unnoticed. In the come up to ASCO, Gilead’s lung cancer drug Trodelvy failed to be statistically significant in a phase 3 trial. J&J’s clinical study witnessed four deaths, which were linked to its radiopharmaceutical JNJ-6420. And, Japanese pharmaceutical Nippon Shinyaku’s drug Viltepso flunked a confirmatory trial in the rare, genetic disorder Duchenne muscular dystrophy (DMD). 

The five-day summit came to a close on June 4th after more than 2500 posters and around 250 oral abstract presentations were showcased. As cancer research and development continues to push forward, there will be more advancements to come.