Docetaxel

Gilead Sciences announced that its Trop-2-directed antibody-drug conjugate (ADC) Trodelvy (sacituzumab govitecan-hziy) missed the primary endpoint of overall survival (OS) in a confirmatory Phase III study of patients with locally advanced or metastatic urothelial cancer (mUC) previously treated with platinum-based chemotherapy and anti-PD-(L)1 therapy.Despite having received accelerated FDA clearance in this indication in 2021 based on the Phase II TROPHY study, Trodelvy’s continued approval could depend on confirmatory trials, including TROPiCS-04, the company indicated. The TROPiCS-04 trial enrolled 711 patients with mUC who were randomised to receive either Trodelvy or one of three standard-of-care chemotherapies - paclitaxel, docetaxel, or vinflunine. The primary endpoint was OS, with progression-free survival (PFS) being a key secondary goal, alongside overall response rate (ORR).Poorer survival, higher AE-related deathsTop-line results showed that Trodelvy failed to hit the main goal of OS improvement compared with chemotherapy in the intention-to-treat population. However, a numerical improvement in OS favouring Trodelvy was noted, along with trends toward improvement in certain pre-specified subgroups and secondary endpoints, including PFS and ORR.Notably, the Trodelvy group had more deaths from adverse events (AEs) seen early in treatment than the chemotherapy group, primarily attributed to neutropenic complications, including infection. The company noted that the ADC’s safety profile in the study was consistent with that seen in previously approved indications and studies. Trodelvy’s label carries a boxed warning highlighting the risk of severe or life-threatening neutropenia. Next stepsRegarding the disparity in AE-related deaths, the drugmaker plans to further analyse these data and emphasise to physicians the value of using granulocyte-colony stimulating factor (G-CSF) to prevent neutropenic complications. Gilead also said it intends to engage with the FDA upon completion of the full data analysis to chart the drug’s path ahead in bladder cancer.The readout marks a second failure for Trodelvy this year after it missed the survival goal in the Phase III EVOKE-01 study for non-small-cell lung cancer. The ADC, which generated global sales of $1.1 billion last year, has also been approved by the FDA for advanced triple-negative breast cancer and HR+/HER2- breast cancer.

Pictured: Chicago landscape oncology collage/Nicole Bean for BioSpace The American Society of Clinical Oncology annual meeting kicks off today in Chicago, with several companies releasing highly anticipated abstracts ahead of time. Here are some that caught our attention: Targeted Oncology Making headlines, Merus experienced a run on its stock with shares rising one-third last Friday after it announced data from a Phase II study indicating that its bispecific antibody petosemtamab in combination with immunotherapy Keytruda produced a 67% response rate in head and neck cancer. The results will be presented at ASCO as a rapid oral abstract session on June 3 at 8 a.m. in room E450b. “Petosemtamab in combination with pembrolizumab (Keytruda) has demonstrated clinically meaningful activity in first line head and neck cancer, with a 67% response rate overall, observed across tumor PD-L1 expression levels and HPV status and with encouraging safety," said Bill Lundberg, the president and CEO of Merus, in a press release ahead of the presentation. Analysts from William Blair reported confidence in the results, writing in a report: “This unprecedented level of activity in metastatic head and neck cancer patients sets petosemtamab as the most effective combination partner for Keytruda in head and neck cancer patients.” Merus plans to initiate a Phase III study later this year. CAR-T Following CAR-T therapy Carvykti’s recent expansion into second line treatment for multiple myeloma, Legend Biotech and Johnson & Johnson are scheduled to present clinical data from the Phase II multicohort CARTITUDE-2 study evaluating the treatment’s safety and efficacy in various multiple myeloma treatment settings and patient populations (abstract #7535, #7505). Carvykti is the first and only B-cell maturation antigen (BCMA)-targeted therapy approved to treat patients with multiple myeloma as early as the first relapse. It was approved by the FDA on April 5 for adult patients with relapsed or refractory multiple myeloma who have received at least one prior line of therapy, including a proteasome inhibitor and an immunomodulatory agent, and are refractory to lenalidomide. “While we expect the updates to be incremental to Legend’s stock, we believe they will further support the use of BCMA CAR-T cell therapies in the early-line setting,” William Blair analyst Sami Corwin wrote in a report. Emerging Oncology and Immunotherapies On June 3, researchers will be presenting Phase II data on Pfizer and Genmab’s Tivdak (tisotumab vedotin) in head and neck squamous cell carcinoma. Analysts from Leerink Partners were encouraged by the data, positing that they “could see antibody drug-conjugates (ADCs) eventually replace chemotherapy in [the] head and neck cancer treatment paradigm, particularly in the second line space,” according to a report. Additionally, analysts “would be keen to see detail on the tolerability, particularly the avoidance of bleeding events, which had been a concern in previous studies evaluating tisotumab vedotin in head and neck cancer,” according to the report. “[Immunotherapies] have the potential to change the lives of patients by changing progressive cancer into a stable disease associated with improved overall survival,” said Paul Peter Tak, president & CEO of Candel Therapeutics, which will present data on its immunotherapy candidate CAN-2409 (ASCO abstract #8634). Tak told BioSpace the data show that in non-small cell lung cancer patients with progressive disease despite immune checkpoint inhibitor therapy, two administrations of CAN-2409 + valacyclovir resulted in a median overall survival of 20.6 months. This compares to the median overall survival of 11.6 months observed with the standard of care docetaxel-based chemotherapy in a similar patient population. Another abstract highlighted by Leerink Partners is Nanobiotix’s Study 1100 (ASCO abstract #6035). The company is evaluating NBTXR3, which is a radioenhancer composed of functionalized hafnium oxide crystalline nanoparticles, and stereotactic body radiation therapy followed by PD-1 inhibitors nivolumab or pembrolizumab in patients with advanced solid tumors. Leerlink noted the “concept of reconstituting some sensitivity to anti-PD-1 therapy in patients who have progressed” is especially of note, considering that most attempts to do so have so far failed. The report adds that analysts are interested in seeing how the company moves forward by teasing out signals from its “hypothesis-generating dataset.” Mollie Barnes is a freelance science writer. Reach her at mollie@100yearsco.com. Follow her on Threads and Instagram @shejustlikedtogo or LinkedIn. See more of her work at molliebarnes.contently.com.