CLINICAL DATA FROM ONGOING PHASE I DOSE ESCALATION AND EXPANSION STUDY OF MONALIZUMAB AND IMFINZI® (DURVALUMAB) IN COLORECTAL cancer PATIENTS PRESENTED AT 2018 ASCO annual meeting
- Updated clinical data show preliminary anti-tumor activity in patients with recurrent/metastatic microsatellite-stable colorectal cancer (MSS-CRC), a population historically unresponsive to PD-1/L1 blockade
- 31% disease control rate at 16 weeks (DCR: % of responses and stable disease) suggests patients may benefit from stabilizing effect - 88% of patients had 2 or more prior lines of therapy for recurrent/metastatic disease
- Data form a basis for exploring the combination with standard of care therapies (SoC) in less heavily pretreated patients
Marseille, France, June 04, 2018, 07:00 AM CEST
Innate Pharma SA (the "Company" - Euronext Paris: FR0010331421 - IPH) today announced updated preliminary clinical data from an ongoing Phase I dose escalation and expansion study evaluating the safety and efficacy of the combination of monalizumab, a first-in-class monoclonal antibody targeting NK and T cell checkpoint receptor NKG2A, with durvalumab in patients with recurrent/metastatic microsatellite-stable colorectal cancer (MSS-CRC). This trial is being conducted by MedImmune, AstraZeneca's global biologics research and development arm, through a co-development and commercialization agreement.
In a poster presentation made at the Gastrointestinal (Colorectal) Cancer session on Sunday, June 3 2018, during the annual meeting of the American Society of Clinical Oncology (ASCO), the combination of monalizumab and durvalumab showed encouraging anti-tumor activity in this difficult-to-treat patient subset.
"The preliminary data so far suggest that the combination of monalizumab and durvalumab may hold promise in some patients with MSS-CRC, a population historically unresponsive to PD-1/L1 therapy", said study investigator Neil H. Segal, MD., PhD., medical oncologist at Memorial Sloan Kettering Cancer Center, New York.
Pierre Dodion, Chief Medical Officer at Innate Pharma, added: "We are encouraged by the preliminary results from the ongoing trial observed in a heavily pretreated MSS-CRC patient population. These data have prompted our partner AstraZeneca/MedImmune to further expand the study with additional patient cohorts to explore the novel combination of this first-in-class antibody, monalizumab, with durvalumab on top of current standard of care therapies in patients with less heavily pretreated disease".
Key findings from the MSS-CRC expansion cohort:
Updated preliminary clinical data on the expansion cohort of microsatellite-stable colorectal cancer patients (MSS-CRC) presented at ASCO are based on the cut-off date of April 23, 2018. Forty patients are evaluable for safety and 39, for efficacy. Thirty five (88%) patients had 2 or more prior lines of therapy for recurrent/metastatic disease. Efficacy data show an overall response rate (ORR) of 8%, with confirmed partial response in 3 patients (8%) and stable disease (SD) in 11 patients (28%), including 3 SD patients with tumor reduction who continued therapy for >200 days. The median duration of response was 16.1 weeks at the cut-off date. Data demonstrated a disease control rate (DCR) of 31% at 16 weeks.
Clinical Activity in MSS-CRC Cohort*
| MSS-CRC |
|Best Overall Response, n (%)|
|Thereof unconfirmed CR||1 (3%)|
|Overall response rate, n (%) [95% CI]||3 (8%) [2-22%]|
|Median duration of response, weeks (95% CI)||16.1 (15.9-NE)|
|Disease control rate at 16 weeks, n (%) [95% CI]||12 (31%) [17-48]|
*data cut as of April 23, 2018
The safety profile of the monalizumab and durvalumab combination was consistent with the monotherapy profiles of each agent. In the MSS-CRC expansion cohort, the most common treatment-related AE included arthralgia (7.5%), increased AST (7.5%), hypothyroidism (7.5%), pruritus (7.5%), and rash (7.5%). Grade 3/4 AE that occurred in three patients were limited to sepsis (n=1, Grade 4) and increased lipase (n=1, Grade 3), that both could be resolved, and increased AST (n=1, Grade 3).
Monalizumab is a first-in-class antibody targeting NKG2A receptors expressed on tumor infiltrating cytotoxic NK and CD8 T lymphocytes.
NKG2A is an inhibitory checkpoint receptor binding HLA-E. By expressing HLA-E, cancer cells can protect themselves from killing by NKG2A+ immune cells. HLA-E is frequently up-regulated on cancer cells of many solid tumors and hematological malignancies. Hence, monalizumab may re-establish a broad anti-tumor response mediated by NK and T cells. Monalizumab may also enhance the cytotoxic potential of other therapeutic antibodies.
Monalizumab is partnered with MedImmune, AstraZeneca's global biologics research and development arm, through a co-development and commercialization agreement. A broad exploratory joint clinical development program is ongoing, focused on investigating monalizumab in combination strategies.
Durvalumab, a human monoclonal antibody directed against PD-L1, blocks PD-L1 interaction with PD-1 and CD80 on T cells, countering the tumor's immune-evading tactics and inducing an immune response.
As part of a broad development program, durvalumab is being investigated as monotherapy and in combination with IO, small molecules, and chemotherapies across a range of tumors and stages of disease.
Colorectal cancer is the 3rd most commonly diagnosed cancer, with 1.65 million new cases and 835,000 deaths per year worldwide (WHO, GLOBOCAN database, 2015). 21% of colorectal cancer cases are metastatic at diagnosis, but given that some patients who are diagnosed with local disease at some point progress, the total number of patients with metastatic disease may account for roughly 50% of all colorectal cancer patients.
Despite advances in chemotherapy regimens in combination with biologics in the treatment of CRC, a significant number of patients progress within 6 months after receiving either first or second-line chemotherapy with or without biological agents such as bevacizumab and cetuximab. Furthermore, among patients who are beyond second line treatment, efficacy data are even worse with low response rates and short progression free survival and overall survival rates. Response rates reported for TAS102 (Lonsurf®) and regorafenib (Stivarga®), 2 approved agents for patients with heavily pretreated CRC, were 1.6 and 1%, respectively. In the TAS102 pivotal trial, median overall survival was 7.1 months (vs 5.3 months for the placebo group); in the regorafenib pivotal trial, median overall survival was 6.4 months (vs 5.0 months for the placebo group). Initial studies with anti-PD-1 or anti-PD-L1 single-agent therapy have yielded limited to no activity in unselected patients with refractory MSS-CRC. Collectively, these data indicate that patients with CRC after 2 lines of chemotherapy with or without biological agents constitute a group with a high unmet medical need.
About Innate Pharma:
Innate Pharma S.A. is a clinical-stage biotechnology company dedicated to improving cancer treatment and clinical outcomes for patients through first-in-class therapeutic antibodies that harness the body's own immune system.
Innate Pharma specializes in immuno-oncology, a new therapeutic field that is changing cancer treatment by mobilizing the power of the body's immune system to recognize and kill cancer cells.
The Company's broad pipeline includes four first-in-class clinical stage antibodies as well as preclinical candidates and technologies that have the potential to address a broad range of cancer indications with high unmet medical needs.
Innate Pharma has pioneered the discovery and development of checkpoint inhibitors, with a unique expertise and understanding of Natural Killer cell biology. This innovative approach has resulted in major alliances with leaders in the biopharmaceutical industry including AstraZeneca, Bristol-Myers Squibb, Novo Nordisk A/S and Sanofi. Innate Pharma is building the foundations to become a fully-integrated biopharmaceutical company.
Based in Marseille, France, Innate Pharma has more than 180 employees and is listed on Euronext Paris.
Learn more about Innate Pharma at www.innate-pharma.com
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This press release contains certain forward-looking statements. Although the company believes its expectations are based on reasonable assumptions, these forward-looking statements are subject to numerous risks and uncertainties, which could cause actual results to differ materially from those anticipated. For a discussion of risks and uncertainties which could cause the company's actual results, financial condition, performance or achievements to differ from those contained in the forward-looking statements, please refer to the Risk Factors ("Facteurs de Risque") section of the Document de Reference prospectus filed with the AMF, which is available on the AMF website (http://www.amf-france.org) or on Innate Pharma's website.
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