ESMO Abstract Leak Reveals Promising NSCLC Therapies from BMS, BeiGene, J&J, Mirati

Lung cancer_iStock, Mohammed Haneefa Nizamudeen

Pictured: Illustration of a tumor in the lungs/iStock, Mohammed Haneefa Nizamudeen

Following an embargo breach, the organizers of the upcoming European Society for Medical Oncology Congress 2023 on Tuesday made available all late-breaking abstracts to be presented during the meeting.

The decision provides an early preview of the results of some of the most highly anticipated trials and promising treatments in the non-small cell lung cancer (NSCLC) space. Bristol Myers Squibb will present data for Opdivo (nivolumab), while Johnson & Johnson will provide a readout from its head-to-head MARIPOSA trial, which pits its Rybrevant (amivantamab) against AstraZeneca’s Tagrisso (osimertinib).

BioSpace provides an overview of these data below but their respective full findings and analyses will be presented at the European Society for Medical Oncology (ESMO) Congress 2023, held Oct. 20 to 24, in Madrid, Spain.

BMS Touts Opdivo Data from CheckMate Studies

Among the leaks were two high-profile Phase III studies from BMS’s CheckMate clinical development program. In CheckMate-77T, neoadjuvant treatment with Opdivo plus chemotherapy before surgery followed by adjuvant post-operative Opdivo, led to a 42% drop in the risk of disease recurrence, progression or death, compared with placebo.

Opdivo treatment also achieved significantly better pathologic complete response and major pathologic response, both secondary endpoints of CheckMate -77T. The study will continue to assess overall survival (OS), another key secondary efficacy metric. Opdivo’s safety profile in the late-stage study was consistent with what had been established in previous studies.

In an exploratory analysis of the second BMS study, dubbed CheckMate-816, three cycles of neoadjuvant Opdivo with chemotherapy achieved a three-year event-free survival rate of 72%, compared with 47% in comparators who received chemotherapy alone.

The PD-1 blocker also showed “promising” OS benefits and reduced the risk of death by 85% at three years, as opposed to 66% with chemotherapy alone. However, OS data from CheckMate-816 is still immature, according to BMS.

Mirati’s Adagrasib Shows Promise as First-Line Therapy

At ESMO, Mirati will present mid-stage data for adagrasib, which in the Phase II KRYSTAL-7 study showed strong first-line promise when combined with Merck’s blockbuster checkpoint inhibitor Keytruda (pembrolizumab).

The combination regimen reached an overall response rate of 63% and disease control rate of 84% in patients with a PD-L1 tumor proportion score of at least 50%. At a median follow-up of 10.1 months, progression-free survival had not yet been reached.

KRYSTAL-7 is assessing adagrasib combined with Keytruda as a first-line treatment option in G12C-mutated KRAS NSCLC patients. The study found the safety profile for adagrasib to be consistent with what had been determined in prior studies. Mirati is eyeing a Phase III trial for the combo treatment in this indication, with enrollment set to start by the end of the year.

Adagrasib won the FDA’s accelerated approval in December 2022 for locally advanced or metastatic NSCLC with the G12C mutation in the KRAS gene. BMS bought Mirati earlier this month for $4.8 billion.

BeiGene’s Tislelizumab Aces Phase III Trial

Late-breaking data for BeiGene’s Phase III RATIONALE 315 study demonstrate that its anti-PD-1 monoclonal antibody tislelizumab, when given with platinum-based chemotherapy before surgery, can elicit a 56.2% major pathological response, as opposed to only 15% in those who received chemotherapy alone.

Pathological complete response, a key secondary endpoint of RATIONALE 315, was also significantly better in patients who received the tislelizumab-based regimen. The study also found BeiGene’s antibody to be well-tolerated, with no new signals of concern detected.

Tislelizumab is a humanized IgG4 monoclonal antibody that targets PD-1 with high affinity and specificity and is designed to minimize the protein’s interaction with Fc-gamma receptors on macrophages. BeiGene is developing tislelizumab in many different cancer types, including NSCLC, gastric cancer and hepatocellular carcinoma.

Last month, the cancer-focused biotech announced that Novartis had returned worldwide rights to tislelizumab, turning its back on a January 2021 agreement to advance the candidate in esophageal squamous cell carcinoma.

J&J’s Rybrevant-Based Combo Challenges AstraZeneca

Also presenting NSCLC data at ESMO 2023 is J&J, whose head-to-head MARIPOSA study found that the combination of Rybrevant and lazertinib could be a stronger treatment option in EGFR-mutated NSCLC than AstraZeneca’s Tagrisso, the current standard.

These results, which will be presented at a Presidential Session on Oct. 23, showed that J&J’s combo cut the risk of disease progression or death by 30% compared with Tagrisso. Median progression-free survival was likewise longer, with respective durations of 23.7 and 16.6 months.

OS was immature at the time of the analysis, but interim findings show a favorable trend in favor of J&J’s regimen.

In terms of safety, MARIPOSA detected a higher rate of adverse events in patients who were given the combination treatment. The only exception was diarrhea, which was more frequent in Tagrisso counterparts.

Venous thromboembolism was elevated for those who received the Rybrevant-lazertinib combo, though episodes were mostly grade one or two and were effectively managed with anticoagulants.

These early data from MARIPOSA suggest that the Rybrevant-lazertinib combination “may represent a new standard of care” in EGFR-mutated advanced NSCLC, the investigators wrote in the abstract.

Tristan Manalac is an independent science writer based in Metro Manila, Philippines. He can be reached at tristan@tristanmanalac.com or tristan.manalac@biospace.com.

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