On August 1, 2022 Innate Pharma SA (Euronext Paris: IPH; Nasdaq: IPHA) ("Innate" or the "Company"), reported that a planned futility interim analysis of the INTERLINK-1 Phase 3 study sponsored by AstraZeneca (LSE/STO/Nasdaq: AZN) did not meet a pre-defined threshold for efficacy (Press release, Innate Pharma, AUG 1, 2022, View Source [SID1234617171]). Based on this result and the recommendation of an Independent Data Monitoring Committee, AstraZeneca has informed Innate that the study will be discontinued. There were no new safety findings. AstraZeneca plan to share the data in due course.

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The INTERLINK-1 study, sponsored by AstraZeneca, evaluated monalizumab in combination with cetuximab vs. cetuximab in patients with recurrent or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN) who have been previously treated with platinum-based chemotherapy and PD-(L)1 inhibitors.

"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. "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 III non-small cell lung cancer setting, as well as the Phase 2 NeoCOAST-2 study in the neoadjuvant early-stage lung cancer setting."

Susan Galbraith, Executive Vice President, Oncology R&D, AstraZeneca, said: "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."

Monalizumab, Innate’s lead partnered asset, is a potentially first-in-class immune checkpoint inhibitor targeting NKG2A receptors expressed on tumor infiltrating cytotoxic CD8+ T cells and NK cells. It is being studied in a Phase 3 clinical study sponsored by AstraZeneca, PACIFIC-9, evaluating durvalumab (PD-L1) in combination with monalizumab or AstraZeneca’s oleclumab (anti-CD73) in patients with unresectable, Stage III non-small cell lung cancer (NSCLC) who have not progressed following definitive platinum-based concurrent chemoradiation therapy.

About INTERLINK-1:

INTERLINK-1 was a global, multi-center, randomized, double-blind Phase 3 study of monalizumab and cetuximab vs. placebo and cetuximab designed to enroll approximately 600 patients with recurrent or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN) who have been previously treated with platinum-based chemotherapy and PD-(L)1 inhibitors ("IO-pretreated").

The primary endpoint was overall survival (OS) in HPV-unrelated participants, with secondary endpoints including OS in all randomized participants, progression-free survival (PFS), overall response rate, duration of response, safety and quality of life. Additional details on the INTERLINK-1 clinical study can be found here.

About monalizumab:

Monalizumab is a potentially first-in-class immune checkpoint inhibitor targeting NKG2A receptors expressed on tumor infiltrating cytotoxic CD8+ T cells and NK cells.

NKG2A is an inhibitory checkpoint receptor for HLA-E. By expressing HLA-E, cancer cells can protect themselves from killing by NKG2A+ immune cells. HLA-E is frequently overexpressed in the cancer cells of many solid tumors and hematological malignancies. Monalizumab may reestablish a broad anti-tumor response mediated by NK and T cells, and may enhance the cytotoxic potential of other therapeutic antibodies.

The ongoing development for monalizumab is focused on investigating monalizumab in various combination strategies in different malignancies, including, in early lung cancer, the Phase 3 PACIFIC-9 study in adults with locally advanced (Stage III), unresectable NSCLC, who have not progressed following platinum-based concurrent chemoradiotherapy, and the Phase 2 NeoCOAST-2 study in the neoadjuvant early-stage setting of NSCLC.

About the Innate-AstraZeneca monalizumab agreement:

In October 2018, AstraZeneca obtained full oncology rights to monalizumab by exercising its option under the co-development and commercialization agreement initiated in 2015.

The financial terms of the agreement include potential cash payments up to $1.275 billion to Innate Pharma. Including the $50 million payment triggered by dosing the first patient in the Phase 3 PACIFIC-9 clinical study, Innate Pharma has received $450 million to date.

For any commercialized oncology indication, AstraZeneca will book all sales revenue and will pay Innate low double-digit to mid-teen percentage royalties on net sales worldwide except in Europe where Innate Pharma will receive 50% share of the profits and losses in the territory. Innate co-fund 30% of the costs of the Phase 3 development program of monalizumab with a pre-agreed limitation of Innate’s financial commitment.