Pictured: A cancer therapeutics collage/Nicole Bean for BioSpace
On February 16, the FDA approved the first one-time cell therapy for a solid tumor and the first tumor-infiltrating lymphocytes therapy. It was a decision one expert said “will unlock more innovation in the industry” and benefit cancer patients.
There has, in fact, been so much innovation in cancer treatment during the past decade that the FDA moved away from the “gold standard” of overall survival in favor of progression-free survival when making approval decisions, though that could now be changing.
Beyond a spate of approvals already granted in 2024, further important readouts for several cancer drugs and vaccines are on the horizon. These include novel therapies for cancers of the bladder, breast, lung and ovary, among others. BioSpace takes a closer look at six clinical trials with anticipated results before the end of the first half of the year.
Daiichi Sankyo and AstraZeneca’s Enhertu
Metastatic breast cancer
Results from the Phase III DESTINY-Breast06 trial assessing AstraZeneca and Daiichi Sankyo’s antibody-drug conjugate (ADC) Enhertu (trastuzumab deruxtecan, or T-DXd) against chemotherapy in HER2-low, hormone receptor–positive metastatic breast cancer, are expected in the first half of 2024, according to a Leerink Partners note provided to BioSpace.
Enhertu, the anchor of Daiichi’s ADC business, brought in more than $1.51 billion in revenue for the company last year.
DESTINY is one of three Phase III breast cancer trials reading out this year, said Leerink Partners analyst Daina Graybosch. Another, TROPION-Breast02, compares Dato-DXd, a TROP2-directed ADC also developed by Astra and Daiichi, with chemotherapy in patients with metastatic triple-negative breast cancer (TNBC). Additionally, topline data from the ASCENT-03 trial of Gilead’s Trodelvy in advanced, inoperable or metastatic TNBC are also expected in 2024.
“You basically have three trials all going with different ADCs for similar indications all reading out together, so it’s actually pretty interesting,” Graybosch told BioSpace.
Gilead’s Trodelvy
Second-line bladder cancer
Sales of Gilead Sciences' Trodelvy, first approved in April 2020 for metastatic TNBC, increased by more than 50% in the fourth quarter of 2023 compared to that quarter a year earlier. And Gilead could enjoy even higher sales if upcoming readouts support additional approvals.
During an investor call earlier this month, Gilead CEO Dan O’Day highlighted an upcoming readout from the Phase III TROPiCS-04 study of Trodelvy in second-line metastatic bladder cancer.
Bladder cancer is an “increasingly important market for Trodelvy," Graybosch said. Notably, she said, TROPiCS-04 is a confirmation trial following Trodelvy’s accelerated approval in locally advanced or metastatic bladder cancer in 2021. “So, if this doesn’t work, they’ll actually lose their bladder [cancer] indication altogether.” She added that earlier results are “promising, but it’s not necessarily a home run that this is definitely going to be successful.”
There is also the possibility, Graybosch noted, that Trodelvy could move into earlier treatment combined with Padcev. “We’ve seen some really interesting data,” she said.
GSK’s Zejula and Jemperli
Ovarian cancer
In December 2023, GSK reported positive topline data from the second part of the Phase III RUBY study, showing that a combination of Jemperli and Zejula met the primary endpoint of improved progression-free survival in patients with advanced or recurrent endometrial cancer. Next up for GSK’s combo: another Phase III readout, this one for ovarian cancer, expected in the first half of 2024.
The randomized, double-blind trial, which began in 2018, compares Zejula and Jemperli plus platinum-based chemotherapy against standard-of-care platinum-based chemotherapy as a first-line treatment for stage 3 or stage 4 non-mucinous epithelial ovarian cancer.
Zejula was approved in April 2020 for the maintenance treatment of patients with advanced epithelial ovarian cancer who have shown a complete or partial response to first-line platinum-based chemotherapy.
Roche’s Tiragolumab and Tecentriq
Non-small cell lung cancer
In August 2023, Roche was compelled to provide early data from the Phase III SKYSCRAPER-01 study of its anti-TIGIT immunotherapy tiragolumab in non-small cell lung cancer (NSCLC) after an “inadvertent disclosure” of the second interim analysis of the study, according to the company’s press release. Roche noted at the time that final overall survival analysis would come either in Q4 2023 or Q1 2024.
SKYSCRAPER-01 is assessing tiragolumab with Tecentriq (atezolizumab) as a first-line treatment option in NSCLC patients with high expression levels of the PD-L1 protein. The study’s two primary efficacy endpoint measures are overall survival and progression-free survival.
As of the second interim analysis disclosed in August 2023, overall survival results were not mature, according to Roche, but the company did report median overall survival estimates of 22.9 months for the tiragolumab/Tecentriq combo compared with 16.7 months for the Tecentriq monotherapy arm. These data were from patients followed for an average of 15.5 months.
Cue Biopharma’s CUE-101
Head and neck cancer
It’s not just the big players that have important upcoming data readouts. Boston-based Cue Biopharma is expecting Phase Ib results for its lead oncology asset, CUE-101. The candidate, a novel therapeutic biologic, is being evaluated in combination with Merck’s Keytruda as a potential first-line treatment for patients with HPV-positive recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC).
CUE-101 is designed to selectively modulate and activate HPV+ T cells to increase efficacy over traditional immunotherapies while reducing side effects typically associated with them. Earlier this month, Cue presented data from the KEYNOTE-040 Phase Ib trial showing that CUE-101 plus Keytruda demonstrated an overall response rate of 47% compared to 19% among patients taking Keytruda alone.
The Phase Ib combination data will form the basis of discussions with the FDA to define a Phase II/III registrational trial, a company representative told BioSpace in an email.
Elicio’s Cancer ELI-002
KRAS/NRAS-mutated solid tumors
Finally, Elicio Therapeutics is expected to present the first-ever data from the 7P formulation of its off-the-shelf cancer vaccine candidate, ELI-002 7P, targeting KRAS/NRAS-mutated solid tumors. The interim data will come from the Phase Ia safety arm of the AMPLIFY-7P trial that was initiated in April 2023.
The therapeutic vaccine, which targets the seven most common KRAS mutations found in around 25% of all solid tumors, is being given as an adjuvant monotherapy. In the Phase II arm of the AMPLIFY-7P study, the investigational vaccine will go up against a particularly deadly foe: pancreatic cancer. The first patient in this arm was dosed in January, with the first data expected in the first quarter of 2025. Positive Phase I data from an earlier formulation of the vaccine, ELI-002 2P, in patients with pancreatic or colorectal cancer, demonstrated tumor biomarker reductions in 84% of patients, tumor biomarker clearance in 24% and T cell responses in 84%.
Several other therapeutic cancer vaccines, targeting melanoma, ovarian, head and neck, pancreatic and non-small lung cancer, are also making their way through clinical trials.
Heather McKenzie is a senior editor at BioSpace. You can reach her at heather.mckenzie@biospace.com. Also follow her on LinkedIn.
