AstraZeneca has launched two pivotal Phase III clinical trials to evaluate rilvegostomig (AZD2936), an experimental immunotherapy agent, in combination therapies for breast and lung cancers. The trials represent a significant investment in advancing novel immunotherapy combinations beyond current standard-of-care treatments.
Breast Cancer Combination Trial
The first Phase III study (D781DC00001) is testing rilvegostomig in combination with trastuzumab deruxtecan (T-DXd, DS-8201a) for breast cancer patients. The trial features a three-arm design comparing different therapeutic approaches.
Arm A evaluates T-DXd plus rilvegostomig administered intravenously every three weeks (Q3W). Arm B tests T-DXd combined with pembrolizumab (Keytruda), also given Q3W. The active comparator arm (Arm C) uses the established regimen of carboplatin, paclitaxel, and pembrolizumab administered Q3W for six cycles, followed by pembrolizumab maintenance therapy every six weeks for 14 cycles.
Treatment in the experimental arms will continue until objective disease progression according to RECIST v1.1 criteria as assessed by investigators and confirmed by blinded independent central review (BICR), or until other discontinuation criteria are met. The control arm allows for pembrolizumab treatment for up to 20 total cycles, approximately 24 months including both combination and maintenance phases.
Lung Cancer Platform Study
The second Phase III trial (D702FC00001) focuses on lung cancer patients and directly compares rilvegostomig against pembrolizumab, both in combination with platinum-based chemotherapy. This head-to-head comparison represents a direct challenge to the current immunotherapy standard of care.
Arm A combines rilvegostomig with platinum-based doublet chemotherapy (carboplatin or cisplatin plus pemetrexed) for up to four cycles, followed by rilvegostomig monotherapy plus pemetrexed maintenance. The active comparator Arm B uses the established pembrolizumab regimen with the same chemotherapy backbone and maintenance approach.
Both treatment regimens follow a 21-day cycle schedule with intravenous administration on Day 1 of each cycle. The platinum agents (carboplatin or cisplatin) are limited to four cycles, while the immunotherapy agents and pemetrexed continue in the maintenance phase.
Treatment Flexibility and Safety Considerations
The breast cancer trial incorporates treatment flexibility to address potential safety concerns. Investigators may extend the carboplatin, paclitaxel, and pembrolizumab combination for up to 10 cycles at their discretion. Additionally, docetaxel can substitute for paclitaxel in patients who experience hypersensitivity reactions that cannot be successfully rechallenged.
Strategic Implications
These Phase III trials position rilvegostomig as a potential competitor to pembrolizumab, one of the most successful immunotherapy agents in oncology. The direct comparison design in the lung cancer study and the inclusion of pembrolizumab arms in the breast cancer trial provide clear benchmarks for evaluating rilvegostomig's therapeutic potential.
The trials' focus on combination therapies reflects the current trend in oncology toward multi-modal treatment approaches. By pairing rilvegostomig with established agents like trastuzumab deruxtecan and platinum-based chemotherapy, AstraZeneca is positioning the drug within proven therapeutic frameworks while potentially offering improved efficacy or tolerability profiles.
