ZOOMRX Global Oncology Panel’s Perspectives

The last couple of months have brought some high-profile developments in non-small cell lung cancer (NSCLC) including critical data released at the World Conference on Lung Cancer (WCLC‘24) as well as new regulatory approvals that can potentially change the landscape of PD-L1-positive and EGFRm advanced NSCLC treatment paradigms.

Following its dramatic press release in June, Summit Therapeutics released the much-anticipated HARMONi-2 data at the WCLC24 aiming to demonstrate the superior efficacy (PFS) of its bispecific ivonescimab over the current standard of care of Keytruda in the 1L PD-L1-positive advanced NSCLC.

The last month also brought several significant FDA approvals in EGFRm advanced NSCLC especially Rybrevant+Lazcluze in 1L and Rybrevant + chemotherapy in 2L, potentially challenging the well-established position of Tagrisso (and Tagrisso + chemotherapy) as the 1L standard of care in EGFRm mNSCLC.

ZoomRx conducted a survey with 100 oncologists in the US (N=50) and EU (N=50) Sept 16-19 to assess the immediate and longer-term impact of these latest developments.

Recent Lung Developments - Awareness & Excitement

Despite the big press release in June and HARMONi-2 recent data presentation at WCLC24, many oncologists in the US and Europe are not aware of HARMONi-2 trial.

The pivotal MARIPOSA trial that led to the approval of Rybrevant+Lazcluze topped the list of trials oncologists are aware of, along with the Dato-DXd TROPION Lung02 trial as well as Nivolumab perioperative vs. adjuvant trial in NSCLC, with large majorities of oncologists in the US and Europe being aware of these trials.  By comparison, fewer oncologists - about 40% - were aware of HARMONi-2 data.


However, when it comes to the impact these trials may have, MARIPOSA and HARMONi-2 receive the highest levels of excitement among those oncologists aware of these developments.  Given the recent approval of Rybrevant + Lazcluze in the US, the excitement about the MARIPOSA study is not surprising.  The excitement about invonescimab data highlights oncologists’ reaction to the meaningful improvement in PFS that the trial demonstrated, with consistent efficacy results across patient subgroups.


Other trials that also captured the attention of oncologists include novel antibody drug conjugates (ADCs) – Datopotamab Deruxtecan and Ifinatamab Deruxtecan as well as the combination of novel agents with Imfinzi, reflecting the strong interest in ADCs as one of the most promising emerging classes of treatments in NSCLC and other solid tumors.

Perspectives on HARMONi-2

If approved, ivonescimab has the potential to challenge Keytruda as the 1L standard of care for patients with PD-L1-positive advanced NSCLC, however, oncologists express some reservations before they are ready to fully commit.

About half of oncologists in the US and Europe say that they would use ivonescimab as their new preferred option for 1L PD-L1 positive patients (non-squamous and squamous) if it were approved; about a third would use the two options equally and another 15% said they would hold on to Keytruda as their preferred 1L choice.


Note: Data for PD-L1 positive advanced squamous advanced NSCLC patients was comparable.

Oncologists mentioned their long-standing experience and trust supported by a long track of clinical evidence with substantial follow-up data available as a main reason for continued use of Keytruda as a preferred option.  Only a few oncologists mentioned the study limitations including the choice of Keytruda monotherapy as a control arm for patients with 1-49% PD-L1 expression (rather than a combination of Keytruda with a chemotherapy) or limited geographic (China only) coverage of the clinical trial.

When asked directly whether the regulatory body (FDA, EMA) should approve ivonescimab based on a single-country trial, the US and EU oncologists were split.  Most (~60% of) US oncologists leaned against the approval based on a single country trial, whereas the EU oncologists were mostly (70%) in favor of the regulatory approval based on a single country trial.