Taking the Temperature: ASCO 2024

While overall this year’s conference was milder than some other years, there were some hot topics and interesting trends worth sharing for those who weren’t able to be there.

Our top magical moment during the conference was the spontaneous applause and standing ovation lasting ten minutes following Dr. David Spiegel’s presentation of the results from the ADRIATIC study, more about that below.

Other than that, we appreciated the opportunity to connect to leading clinicians and industry experts who provided some color and deeper insights to the top-line announcement and emerging technologies.

Below are the aMoon top three takeaways from the event:

1. Next-generation therapies are still hot

An exceptional presentation by Dr. Patricia LoRusso set the tone for the discussion on Antibody-Drug Conjugates (ADCs). Highlighting key challenges, including multifactorial resistance mechanisms, the therapeutic window, and improving the prediction of patient responses. With 190 assets currently in clinical development and a history of 148 discontinued assets, there is much to learn from past experiences, and as investors, we are looking forward to seeing how these learnings will affect next generations ADCs.

The conference showcased several innovative approaches, and a few new mechanisms of action, along with new data on consolidating targets. For instance, 4-1BB, a target in development for over a decade, had six clinical assets presented this year. Additionally, Pfizer’s asset targeting KAT6 showed early promise in a phase 1 trial for ER-positive, HER2-negative breast cancer patients.

Meanwhile, in the late-stage arena, GSK announced exciting results from the DREAMM-8 phase III trial for their potential blockbuster ADC, Blenrep. The development journey of Blenrep reinforces the reality that the path to clinical trial success and ADC approval can still be long and winding, especially with a moving landscape of treatment options.

Finally, radiopharmaceutical therapy (RPT) remains one of the hottest areas in precision targeting. Just before ASCO, Novartis announced its acquisition of Mariana Oncology for a potential deal value of $1.75 billion. In the conference itself there was a substantial body of clinical experience shared, especially with Lu-177 but also the emerging landscape of Act-225 radiotherapy. The mixed results seen with J&J’s anti-hK2 antibody-based targeted radioligand therapy (which showed profound and durable responses but also resulted in four patient deaths) are an interesting case study, and we are looking forward to following up on this target.

2. Winds of change from the East

Walking through the poster area at ASCO this year, it was evident that China’s biotech industry is taking a leap forward, with numerous China-based pharmaceutical companies (Alphamab Oncology, MedLink Tx, Biotheus, and others) presenting data for novel assets.

Merck’s announcement of positive data for its TROP2-targeting ADC sacituzumab tirumotecan, licensed from China-based Sichuan Kelun-Biotech Pharmaceuticals was another great early sign of quality and potential from the growing industry.

However, just off-conference at the STAT event, the FDA’s top oncologist, Dr. Richard Padzur, advised drugmakers to avoid applying for approval with data from a single country, and reiterated the agency’s preference for data from multi-regional trials. This came after Summit Therapeutics announced that its investigational drug ivonescimab, a bispecific antibody from China, beat Merck’s blockbuster Keytruda in a head-to-head, non-small cell lung cancer study in China. Are the ivonescimab results a paradigm shift or might the data be biased by the patient population? The jury is still out.

3. Success rains down on recent lung cancer clinical trials

It was a year full of promising new advancements for lung cancer, and these culminated in several exciting, practice-changing ASCO updates.

Dr. David Spiegel’s presentation of the ADRIATIC study results, to which we referred in the opening, came after decades with no major advances in the treatment of limited-stage small cell lung carcinoma (LS-SCLC). The ADRIATIC study, run in 19 different countries with 730 patients enrolled, demonstrated that AstraZeneca’s immunotherapy durvalumab extended patients’ lives by over 22 months and can be used as a new SOC for consolidation treatment.

Other exciting developments included: Amgen’s IMDELLTRA (tarlatamab) which received FDA accelerated approval in ES-SCLC; AstraZeneca reported its kinase inhibitor Tagrisso success in a phase 3 trial (LAURA), showing it is cutting the risk of disease progression by 84% compared to placebo; Pfizer’s 5 years follow up of patients with the ALK mutation (phase 3) showed Lorbrena reduced the risk of disease progression in patients with non-small cell lung cancer (NSCLC) by 81%, compared to Xalkori, a drug recognized as a first-line standard of care as well as the ADRIATIC study results, mentioned above.

According to some, ASCO 2024 will be remembered as ‘The Lung ASCO’.

The forecast for next year looks promising

While not the hottest ASCO on record, 2024 was a warm one, with maturing modalities and incremental progress. There were a few meaningful clinical advances, an emphasized need for optimized therapies and patient-centric approaches, with some of these expected to come to fruition in the coming year.

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