Summit Therapeutics Stock Nosedives on Mixed NSCLC Study Results

Shares of Summit Therapeutics SMMT tanked nearly 31% on Friday after it reported mixed results from the phase III HARMONi study, which evaluated its investigational antibody ivonescimab in certain patients with non-small cell lung cancer (NSCLC).

While data from this study showed that the treatment with the drug plus chemotherapy cut the risk of disease progression by 48% compared with chemotherapy alone, it did not achieve “a statistically significant benefit” in the overall survival (OS) endpoint, which is considered the ‘gold standard’ in oncology studies.

More on SMMT’s HARMONi Study Results

The HARMONi study enrolled patients with EGFR-mutated, locally advanced or metastatic non-squamous NSCLC who had progressed after treatment with an EGFR-TKI. The study assessed two primary endpoints — progression-free survival (PFS) and OS.

While the study demonstrated a statistically significant and clinically meaningful improvement in the PFS endpoint, the results only showed a “positive trend” for OS. Though Summit Therapeutics’ combination therapy did reduce the risk of death by 21%, the results were not statistically significant.

These results were also consistent with the HARMONi-A study conducted by Summit’s partner Akeso, which evaluated the combination of ivonescimab plus chemo in a patient population similar to the company’s HARMONi study. Summit in-licensed the right to develop and market the drug in 2022 across several territories, including the United States and Europe.

Unlike the HARMONi-A study, which was conducted exclusively in China, SMMT’s HARMONi study was conducted in a multi-regional setting. Per the company, around 38% of the patients were randomized from Western countries.

SMMT Stock’s Performance

Summit shares plunged following the HARMONi data, likely due to uncertainty around the regulatory path forward. While the company intends to file for approval of the ivonescimab-chemo combination in previously treated EGFR-mutated NSCLC, the FDA has indicated that a statistically significant OS benefit is required to support marketing authorization. As such, Summit said that it would consider the study results and ongoing discussions with the agency to determine the timing of its filing.

However, Wall Street expressed optimism about the OS results. Some analysts noted that many Western patients had not yet reached median OS, suggesting the OS benefit could become clearer with more follow-up. Summit also highlighted that no FDA-approved regimens have yet demonstrated a statistically significant OS benefit in this NSCLC setting.

Year to date, the stock has gained 2% against the industry’s 2% decline.

Recent Developments With SMMT’s Ivonescimab

Summit Therapeutics came into the investor spotlight last year after reporting encouraging results from the HARMONi-2 study, which evaluated ivonescimab against Merck’s MRK blockbuster PD-1 inhibitor Keytruda in patients with locally advanced or metastatic NSCLC whose tumors have positive PD-L1 expression. Treatment with the drug cut the risk of disease progression or death by nearly half compared with Keytruda.

In April, SMMT reported positive results from the Akeso-sponsored phase III HARMONi-6 study, which evaluated ivonescimab plus chemotherapy against BeiGene’s PD-1 inhibitor Tevimbra plus chemotherapy in patients with locally advanced or metastatic squamous NSCLC, regardless of PD-L1 expression. The study met its primary endpoint of PFS — patients treated with the ivonescimab regimen showed statistically significant and clinically meaningful improvement over those who received the Tevimbra combination regimen.

Based on the above results, we believe that ivonescimab could replace PD-(L)1 inhibitors as the next standard of care across multiple NSCLC settings. Unlike Keytruda/Tevimbra, which targets the PD-1 protein, the Summit drug is a first-in-class bispecific antibody that targets two proteins, namely PD-1 and VEGF. We believe that this dual mechanism differentiates ivonescimab from currently available therapies for solid tumors as there is a potentially higher expression of both these proteins in tumor tissue compared with the normal tissues in the body.

Currently, ivonescimab is only approved in China to treat two distinct NSCLC indications. Apart from HARMONi, Summit is conducting two more late-stage studies on the drug in separate NSCLC settings. Both studies are currently enrolling patients.

Therapies Rivaling SMMT’s Ivonescimab

Developing bispecific antibodies that target two proteins, namely PD-1 and VEGF, has lately been one of the lucrative areas in cancer treatment. Companies like BioNTech BNTX and Instil Bio TIL are also developing their respective PD-1/VEGF-targeting antibody candidates, namely BNT327 and AXN-2510.

In November, Merck signed a deal with China-based LaNova Medicines for the latter’s LM-299, which is also based on the same mechanism as ivonescimab. Merck intends to advance the drug's clinical development “with speed and rigor for patients in need.”

The latest entrant into this space is Pfizer, which recently entered a multi-billion-dollar deal with Chinese biotech 3SBio for the latter’s PD-1/VEGF bispecific antibody SSGJ-707. The deal is expected to be complete in third-quarter 2025.

Despite the competition, we believe that Summit enjoys the advantage of being ahead in clinical development over the BioNTech, Instil Bio, Merck and Pfizer therapies. These candidates are still at least a year away from reaching the same clinical development position as SMMT.

Summit Therapeutics PLC Price

 

 

Summit Therapeutics PLC price | Summit Therapeutics PLC Quote

SMMT’s Zacks Rank

Summit currently carries a Zacks Rank #2 (Buy). You can see the complete list of today’s Zacks #1 Rank (Strong Buy) stocks here.

Want the latest recommendations from Zacks Investment Research? Today, you can download 7 Best Stocks for the Next 30 Days. Click to get this free report

This article originally published on Zacks Investment Research (zacks.com).

Zacks Investment Research