Spotlight On: Five things to watch at ESMO 2021

The European Society for Medical Oncology (ESMO) congress takes place later this week (16-21 September). We highlight five important stories to keep an eye on…

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Can adagrasib shine in CRC?

Mirati Therapeutics will present updated results from the Phase I/II KRYSTAL study evaluating adagrasib in KRAS-mutated solid tumours, with the primary focus among investors likely to be new data in colorectal cancer (CRC).

Amgen's Lumakras became the first KRAS inhibitor to secure regulatory approval (in the US) earlier this year, specifically to treat certain non-small-cell lung cancer (NSCLC) patients – where adoption is expected to be swift – but has underwhelmed in CRC as a monotherapy.

Mirati's previous update showed a higher 17% response rate for adagrasib in KRAS-mutated CRC, suggesting a potential opportunity for differentiation versus Lumakras.

Validated by Amgen and Mirati's early progress, other Big Pharma companies are now piling into the KRAS field in the hope of delivering better second-generation agents.

Further momentum for Enhertu

AstraZeneca paid big bucks to in-license the HER2 antibody-drug conjugate (ADC) Enhertu from Daiichi Sankyo back in 2019 and the drug has continued to deliver regulatory and clinical progress since.

Most recently, AstraZeneca confirmed last month that Enhertu demonstrated superiority over Roche's ADC Kadcyla in second-line HER2-positive breast cancer and these data (from the Destiny-Breast 03 study) will be presented at ESMO on Saturday during the meeting's first plenary session.

Language used in AstraZeneca's press release suggests a clear benefit over Kadcyla, which generates annual sales of approximately $1 billion in the second-line setting, estimate analysts at Jefferies. 

See – KOL Views Q&A: Second-line is just the beginning for Enhertu in HER2+ breast cancer, says leading oncologist

Clinical validation for EQRx

September has delivered a double header for sugemalimab, the PD-L1 inhibitor being developed by CStone Therapeutics and EQRx.

At the World Conference on Lung Cancer (WCLC) meeting this week new data presented in metastatic NSCLC suggests that sugemalimab is potentially more efficacious than Merck & Co.'s all conquering PD-1 inhibitor.

A notable outcome, as EQRx is looking to launch sugemalimab in western markets and compete with Big Pharma on price.

See – Spotlight On Interview: Is the drug pricing disruptor EQRx about to come of age?

This weekend at ESMO, positive data for sugemalimab in Stage III NSCLC patients (top-lined as positive in May) will be presented, providing further momentum for one of the most intriguing cancer immunotherapies in late-stage development and potentiallt pitching it as a competitor to AstraZeneca's Imfinzi; currently the only approved PD-(L)1 inhibitor for Stage III NSCLC.

See – ViewPoints: EQRx scores a potentially big win for its low-cost drive in lung cancer

In another late-breaking presentation at ESMO, data from AstraZeneca's Phase II COAST trial will highlight progression-free survival (PFS) results for novel Imfinzi combinations with potential new medicines including oleclumab, an anti-CD73 monoclonal antibody, and monalizumab, an anti-NKG2A monoclonal antibody, in unresectable, Stage III NSCLC. These combinations aim to build on the PACIFIC Phase III trial results that established Imfinzi as the standard of care in this setting.

King Keytruda

On the subject of Keytruda, detailed results – including overall survival (OS) data – will be presented from Keynote-355, evaluating its use in combination with chemotherapy for the first-line treatment of metastatic triple-negative breast cancer (in patients whose tumours express PD-L1 with a combined positive score (CPS) ≥10).

Confirming a top-line positive OS result in May, Merck noted that Keytruda is the first PD-(L)1 inhibitor to demonstrate a significant survival benefit (with chemotherapy) in this patient population.

Keytruda's likely dominance of the metastatic TNBC market has been further enhanced by Roche's decision to voluntarily drop the metastatic TNBC indication for its PD-L1 inhibitor Tecentriq in the US market following consultation with the FDA.

Initially granted accelerated approval, Tecentriq subsequently failed to show a survival benefit in PD-L1 positive patients. US market withdrawal was prompted in part by Keytruda's approvals for both first-line metastatic TNBC and high risk, early-stage TNBC.

Elsewhere at ESMO, data for Keytruda will be presented from Keynote-826 in first-line cervical cancer. Used in combination with chemotherapy and Roche's Avastin, Keytruda is the first immunotherapy to have demonstrated meaningful improvements in OS and progression-free survival in this setting.

Another sneak peek at Roche's SERD

The race to develop novel SERDs for the treatment of breast cancer has become increasingly competitive with AstraZeneca, Sanofi and Roche all vying for superiority.

At an R&D event yesterday, Roche highlighted Phase II data for its agent giredestrant (plus Pfizer's CDK4/6 inhibitor Ibrance) in neoadjuvant ER-positive breast cancer, which will be presented on Monday and will be the first data for any of the novel SERDs in pre-metastatic disease.

Echoing claims made by its competitors, Roche argues that giredestrant is a best-in-class agent and says it could be up to 15-times more potent than other SERDs in mid-to-late stage development.

Management reiterated this week that it is hopeful giredestrant can replace endocrine therapy across all lines of treatment for ER-positive breast cancer. In addition to the neoadjuvant data at ESMO, pivotal Phase II data in second- and third-line patients is expected next year.

Sanofi is ahead of the competition and expected to announce its second- and third-line pivotal-stage data by the end of 2021.

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