Phase 3 INTERLINK-1 Trial of Monalizumab Plus Cetuximab in Recurrent or Metastatic HNSCC Discontinued

Findings from the planned futility interim analysis of the phase 3 INTERLINK-1 trial has led to the study’s termination after monalizumab and cetuximab did not meet efficacy end points in recurrent or metastatic squamous cell carcinoma in the head and neck.

The phase 3 INTERLINK-1 trial’s (NCT04590963) planned futility interim analysis, assessing monalizumab plus cetuximab (Erbitux) vs cetuximab alone for patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) who have previously been treated with platinum-based chemotherapy and PD-L1 inhibitors, indicated that the trial’s primary end points were missed, according to a press release from Innate Pharmaceuticals. This has led to the trial’s termination.

The recommendation came from an independent data monitoring committee, leading to AstraZeneca informing Innate of the trial’s discontinuation. No new safety findings were reported, and additional data will be shared, AstraZeneca stated.

“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,” Mondher Mahjoubi, chief executive officer at Innate Pharma, said in the press release.

Monalizumab is a first-in-class immune checkpoint inhibitor that targets the NKG2A receptors that are expressed on tumor-infiltrating cytotoxic CD8-positive T cells and natural killer cells. Monalizumab is also being studied in the phase 3 PACIFIC-9 trial (NCT052218490) in combination with durvalumab (Imfinzi) or oleclumab (MEDI9447) for those with unresectable stage III non–small cell lung cancer who have not progressed on platinum-based concurrent chemoradiation therapy.

Investigators intended to enroll about 600 patients with recurrent or metastatic HNSCCC who have previously been treated with platinum-based chemotherapy and PD-L1 inhibitors. The primary end point was overall survival (OS) for those who with human papillomavirus–unrelated disease. The secondary end points were OS in all patients, progression-free survival, overall response rate, duration of response, safety, and quality of life.

To be included in this trial, patients were required to be 18 years or older with recurrent or metastatic disease that had progressed on or after previous treatment and was not amenable to curative therapy. Patients must have had a prior platinum failure, received 1 or 2 prior systemic regimens, have measurable disease, recent tumor tissue for biomarker testing, and World Health Organization/ECOG performance status of 0 or 1.

Exclusion criteria included having head and neck cancer in a primary anatomic location not specified in the inclusion criteria, receipt of prior cetuximab therapy, active or prior documented autoimmune or inflammatory disorders, diverticulitis, or any concurrent anticancer treatment besides hormonal therapy for non-cancer-related conditions.

“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 [NSCLC] across different trials, including the phase 3 PACIFIC-9 trial,” Susan Galbraith, executive vice president of Oncology Research & Development at AstraZeneca, concluded.


Innate Pharma provides update on AstraZeneca-sponsored INTERLINK-1 phase 3 study. News Release. August 1, 2022. Accessed August 3, 2022.