Neoadjuvant tremelimumab plus durvalumab displayed encouraging activity and a favourable safety profile in patients with microsatellite instability-high (MSI-H), resectable gastric or gastroesophageal junction adenocarcinoma (GAC/GEJAC) in the phase 2 INFINITY trial
In patients with GAC/GEJAC, MSI-H status has been linked to improved survival outcomes and a reduced benefit from chemotherapy . On the other hand, immunotherapy is effective in MSI-H tumours . Therefore, the combination of CTLA-4 inhibition and PD-L1 inhibition may result in the possibility of omitting chemotherapy or surgery in these patients.
The multicentre, single-arm, phase 2 INFINITY trial (NCT04817826) assessed the efficacy and safety of tremelimumab plus durvalumab as neoadjuvant therapy in a cohort of 18 patients with MSI-H, mismatch repair deficient (dMMR), and EBV-negative resectable GAC/GEJAC . In a second cohort, this therapy will be assessed as a definitive treatment for patients with this indication. In the neoadjuvant cohort, patients received a single dose of 300 mg tremelimumab and 1,500 mg durvalumab, every 4 weeks. The primary endpoint was the pathological complete response (pCR) with negative ctDNA after 12 weeks of treatment. Dr Filippo Pietrantonio (Fondazione IRCCS Istituto Nazionale dei Tumori, Italy) presented the findings .
In total, 9 out of 15 evaluable patients achieved a pCR with negative ctDNA status (60%) prior to surgery. The major-complete pathological response rate (<10% viable cells) was 80%. According to Dr Pietrantonio, the global quality-of-life was preserved during the neoadjuvant treatment.
Pre-operative treatment with tremelimumab and durvalumab was generally safe. In 3 patients, grade ≥3 immune-related adverse events (AEs) occurred; hepatitis, colitis, and pneumonitis, one case each. The most common grade 1 or 2 AEs were pruritis (22%), thyroiditis (22%), hepatitis (17%), and skin rash (17%).
The combination of tremelimumab and durvalumab appeared to be safe and displayed encouraging activity in the current phase 2 trial. “Although larger studies are needed, chemotherapy-free, immune checkpoint inhibitor-based strategies will represent a standard-of-care in the molecular subgroup of MSI-H dMMR tumours in the foreseeable future,” argued Dr Pietrantonio. “Of course, optimal combinations and therapy duration should be further investigated.” This data is important for potential non-operative management as in locally advanced rectal cancer.
- Pietrantonio F, et al. JCO. 2019;37(35):3392–3400.
- Leone AG, et al. ESMO Open. 2022;7(1):100380.
- Pietrantonio F, et al. INFINITY: A multicentre, single-arm, multi-cohort, phase II trial of tremelimumab and durvalumab as neoadjuvant treatment of patients with microsatellite instability-high (MSI) resectable gastric or gastroesophageal junction adenocarcinoma (GAC/GEJAC). Abstract 358, ASCO GI 2023, 19–21 January, San Francisco, CA, USA.
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Table of Contents: ASCO GI 2023
Letter from the Editor
ASCO GI 2023 Highlights Podcast
Oesophageal and Gastric Cancer
Zolbetuximab plus mFOLFOX6 successful in CLDN18.2-positive subgroup of gastric cancer
Regorafenib offers survival benefit for patients with pre-treated gastric cancer
Radiotherapy or not in locally advanced oesophageal or junctional cancer?
Neoadjuvant immunotherapy is safe and efficacious in a phase 2 gastric cancer trial
S-1 adjuvant chemotherapy: 4 or 8 courses in stage 2 gastric cancer?
LATG/LAPG demonstrates excellent long-term efficacy in stage 1 gastric cancer
3-year follow-up data confirms benefits of nivolumab plus chemotherapy
Long-term results for nivolumab plus chemotherapy and nivolumab plus ipilimumab in oesophageal cancer
Promising phase 2 results for HER-Vaxx in gastric cancer
Anal and Colorectal Cancer
IMbrave 151 missed primary endpoint in advanced BTC
Combination botensilimab plus balstilimab demonstrates promising activity in heavily pre-treated MSS CRC
Mutation-based selection to identify patients suitable for panitumumab treatment
Fucoidan associated with quality-of-life benefits in patients with rectal cancer receiving CCRT
ctDNA appears useful in monitoring patients with anal cancer undergoing CRT
SUNLIGHT trial meets primary endpoint in refractory metastatic CRC
Does cell-free DNA influence MRD testing in post-operative colon cancer?
OPERA: surgery may be avoided with adequate therapy in rectal cancer
Can we improve total neoadjuvant therapy for rectal cancer?
Palliative radiation therapy improves hepatic pain in HCC and liver metastasis
Improved survival following postoperative sorafenib plus TACE in HCC
Quality-of-life benefits for tislelizumab in uHCC
Stereotactic body radiation therapy beneficial for patients with locally advanced HCC
SWOG 1815, first-ever phase 3 trial in BTC, fails
Acceptable safety profile and encouraging efficacy of nanvuranlat in BTC
First-line NALIRIFOX superior to standard treatment in mPDAC
Novel approach delivers quality-of-life benefits for patients with pancreatic cancer