The phase 3 INTERLINK-1 study of monalizumab and cetuximab as treatment of recurrent or metastatic squamous cell carcinoma of the head and neck has been discontinued. The study did not meet its efficacy goal.
In the phase 3 INTERLINK-1 study (NCT04590963), the combination of monalizumab and cetuximab (Erbitux) did not improve overall survival (OS) in patients with recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN) who have been previously treated with platinum-based chemotherapy and PD-L1 inhibitor.1
Results announced in a press release by AstraZeneca showed that the trial missed its a pre-defined threshold for efficacy and showed no new safety signals. The trial has been discontinued due the result and per the recommendation of the Independent Data Monitoring Committee. Data from the study will be shared later.
"The INTERLINK-1 phase 3 study was intended to further evaluate a novel immunotherapy regimen following the promising signals observed in a non-randomized phase 1b/2 study of head and neck cancer. While we are disappointed with the outcome of this study, the findings are certain to advance our understanding of the role of immunotherapy in this setting," said Mondher Mahjoubi, chief executive officer of Innate Pharma, in a press release. "We remain confident in the development program for monalizumab in lung cancer, where encouraging data has been previously reported from the randomized, phase 2 COAST and Neo-COAST studies. Our focus for monalizumab remains on the phase 3 PACIFIC-9 study in the unresectable stage 3 non–small cell lung cancer setting, as well as the phase 2 NeoCOAST-2 study in the neoadjuvant early-stage lung cancer setting."
INTERLINK-1 was a randomized, double-blind, multicenter, global study of about 624 patients with recurrent or metastatic SCCHN. In addition to OS, the study was assessing progression-free survival, disease-related symptoms, the immunogenicity of monalizumab, the association of natural killer cell-related protein markers with efficacy endpoints, adverse events, objective response rate, duration of response, and pharmacokinetics.2
Patients eligible to be treated in the INTERLINK-1 were at least 18 years of age with recurrent or metastatic SCCHN who have received a prior treatment using a PD-L1 inhibitor, failed on platinum-based chemotherapy, and received 1 or 2 prior systemic regimens for recurrent or metastatic SCCHN. All patients were required to have measurable disease per RECIST 1.1, a WHO performance status of 0 or 1, and have fresh tissue available for biopsy.
The study excluded patients with head and neck cancer of any primary anatomic location in the head and neck that was not specified in the inclusion criteria, as well as patients who received prior cetuximab, had active or prior documented autoimmune or inflammatory disorders, or who were receiving any concurrent anticancer treatment.
“We are disappointed by this outcome and what it means for patients. We would like to thank the patients, investigators and healthcare professionals who dedicated their time and expertise to this trial, which has advanced our understanding of metastatic head and neck cancer. We continue to explore the impact of monalizumab in patients with non-small cell lung cancer across different trials, including the phase 3 PACIFIC-9 trial,” said Susan Galbraith, executive vice president, Oncology R&D, AstraZeneca, in the press release.1
The double-blind, placebo-controlled, randomize, multicenter, international PACIFIC-9 study (NCT05221840) recently administered durvalumab (Imfinzi) in combination with either the humanized anti-NKG2A monoclonal antibody monalizumab, or the anti-CD73 monoclonal antibody, oleclumab to its first patient with unresectable, stage III non–small cell lung cancer. The target completion date for the study is May 31, 2030.3
1. Innate pharma provides update on astrazeneca-sponsored INTERLINK-1 phase 3 study. News release. Innate Pharma. August 1, 2022. Accessed August 1, 2022. https://bit.ly/3cVPedg
2. Assessment of efficacy and safety of monalizumab plus cetuximab compared to placebo plus cetuximab in recurrent or metastatic head and neck cancer (INTERLINK-1). ClinicalTrials.gov. Updated July 26, 2022. Accessed August 1, 2022. https://clinicaltrials.gov/ct2/show/NCT04590963?term=INTERLINK-1&draw=2&rank=1
3. First patient dosed in monalizumab phase 3 lung cancer clinical trial triggers $50m payment from astrazeneca. News release. Innate Pharma. April 29, 2022. Accessed May 3, 2022. https://bit.ly/3OReiRc