5 Successful Phase III Oncology Trials in Q1

In the oncology space, drug developers are keen to develop cutting-edge solutions—and lay claim to a piece of a market estimated to hit $359.1 billion by 2028. However, most Phase III trials fail to present significant clinical improvements on the standard of care.

“Oncology . . . is huge because there are some successes, but there’s still a huge medical need,” Ansbert Gadicke, managing partner at MPM BioImpact, told BioSpace earlier this year.

Vlad Vitoc, CEO of the immune-oncology company MAIA Biotechnology, concurred. “These trials are important for the niche patient populations they serve,” he told BioSpace. Vitoc lauded successful recent Phase III trial successes as welcome advancements, noting that they will improve care options for patients beyond what is currently available.

Here, we highlight five such trials with game-changing potential for oncology and the potential to influence the current market.

Bristol Myers Squibb is knocking on the door of a liver cancer market currently led by AstraZeneca and Roche. In March, BMS revealed that Opdivo and Yervoy improved survival in patients with untreated advanced hepatocellular carcinoma (HCC) in the Phase III CheckMate-9DW trial compared to the investigator’s choice of therapy sorafenib or lenvatinib.

The Checkmate-9DW trial comprised 700 people with untreated advanced HCC given BMS’s combo or sorafenib or lenvatinib. The study hit its primary overall endpoint, with interim analysis showing that patients in the Opdivo and Yervoy arm were living longer than those in the control arm.

An FDA approval of the Opdivo/Yervoy combo would position BMS to compete in the first-line liver cancer market alongside Roche and AstraZeneca. Roche’s checkpoint inhibitor Tecentriq was approved by the FDA in combination with VEGF inhibitor Avastin in 2020. Two years later, AstraZeneca won approval for Imjudo combined with Imfinzi.

Also last month, Pfizer recorded positive results from a Phase III trial for its Adcetris regimen in patients with relapsed or refractory diffuse large B cell lymphoma (DLBCL). Adcetris—an antibody-drug conjugate (ADC) known as brentuximab vedotin—combined with lenalidomide and rituximab showed “statistically significant and clinically meaningful” improvements in overall survival, the trial’s primary endpoint, compared to lenalidomide and rituximab plus placebo. Adcetris also showed significant improvement in the secondary endpoints of progression-free survival (PFS) and overall response rate (ORR).

While full data from the ECHELON-3 trial have not yet been shared, Pfizer said Adcetris’s safety and tolerability were consistent with previous findings recorded with the drug when used to treat patients with refractory or relapsed DLBCL. With these data in hand, Pfizer will engage with the FDA regarding a regulatory submission, according to the press release. An approval would mark the eighth indication for Adcetris, which was initially approved in 2011.

There could soon be a non-surgical option for cervical high-grade squamous intraepithelial lesions (HSIL). On March 18, Chinese biopharma Asieris Pharmaceuticals reported that treatment with its cold light photodynamic drug-device combination APL-1702 demonstrated significant efficacy in a Phase III trial, with advancements in high-risk HPV16 and HPV18 clearance rates.

Patients treated with APL-1702 showed a statistically significant improvement of 89.4% compared to the placebo control group, Asieris stated in its announcement. The product had a “good” safety profile, according to the company. The trial included 402 eligible patients from across China, Germany and the Netherlands, among other countries.

Cervical cancer is the fourth most common cancer in women. Its primary cause is human papillomavirus infection, which causes cervical lesions. Experts project that by 2030, around 16 million people will have HSIL worldwide.

An innovative treatment is showing promise in treating brain metastases from NSCLC. Last month, Swiss biotech Novocure reported its Tumor Treating Fields (TTFields) therapy met the primary endpoint in the Phase III METIS clinical trial, demonstrating a statistically significant improvement in time to intracranial progression when combined with supportive care compared to supportive care alone. TTFields uses electric fields that act via many different mechanisms to kill cancer cells.

The trial consisted of 298 adult patients with up to 10 brain metastases from NSCLC following stereotactic radiosurgery who received either TTFields or supportive care, including treatments with steroids, anti-coagulants, anti-epileptic drugs, pain control and nausea control. If a second intracranial progression was confirmed, patients were allowed to cross over to the experimental arm.

Treatment with the therapy was well-tolerated, with sustained quality of life and neurocognitive functions, according to Novocure.

TTFields was first approved by the FDA in 2011 for the treatment of recurrent glioblastoma and Novocure CMO Nicolas Leupin said the company continues to explore the capabilities of this therapy in a variety of solid tumor types. “At Novocure, we pursue aggressive, difficult to treat cancers because we are passionate about helping patients and we believe in the science of TTFields therapy,” Leupin told Biospace.

Finally, in January, Roche subsidiary Genentech posted positive Phase III data for its anti-TIGIT immunotherapy tiragolumab when used in combination with Tecentriq and chemotherapy. The SKYSCRAPER-08 study, one of seven Phase III trials ongoing for tiragolumab, enrolled 461 patients with esophageal squamous cell carcinoma (ESCC) from Asian countries randomized into a treatment arm and control arm. Tiragolumab combined with Tecentriq and chemotherapy improved PFS compared to chemo alone.

The anti-TIGIT market has been a challenging one to crack, with other key players failing to meet their targets. Novartis ended its partnership with BeiGene for an anti-TIGIT therapy in non-small cell lung cancer (NSCLC) last year, taking a $300 million loss. Merck’s Keytruda plus anti-TIGIT vibostolimab also failed to meet the primary endpoints in a Phase II NSCLC study in 2023.

Gilead and Arcus Biosciences have fared better, recording “encouraging results” in a Phase II trial for domvanalimab, an Fc-silent anti-TIGIT antibody, used in combination with the anti-PD-1asset zimberelimab and chemo in patients with upper GI cancers, according to the partners’ November 2023 announcement.

Further growth in the anti-TIGIT market is anticipated, with more than 40 anti-TIGIT antibodies in clinical trials around the world.

Nsisong Asanga is a physician, field epidemiologist, and freelance health writer. You can reach her on LinkedIn.