Monday, June 4, 2018 - 07:00
  • 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  

 

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

(n=39)

Best Overall Response, n (%)

 

           CR

0

            PR

3 (8%)

                   Thereof unconfirmed CR

1 (3%)

            SD

11 (28%)

            PD

22 (56%)

            NE/NA

3 (8%)

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).