Combination Study of IPH2201 (Monalizumab) With Ibrutinib in Relapsed, Refractory or Previously Untreated CLL

Number of dose-limiting toxicities, measured during the phase 1, dose escalation, part of the study.

Time frame: 8 weeks

Population: During phase 1 part of the study (dose escalation) the total number of patients evaluated for safety parameters is 13; 3 patients received at least one dose of monalizumab 1 mg/kg, 6 patients received 2 mg/kg , and 4 patients received 4 mg/kg.

The rate of complete response (CR) was evaluated using the International Workshop on Chronic Lymphocytic Leukemia (IWCLL) grading scale and confirmed by a bone marrow biopsy. Per International Workshop on Chronic Lymphocytic Leukemia (IWCLL), Complete Response (CR) is defined as lymphocytes \<4x109/l, absence of lymphadenopathy, hepatomegaly and splenomegaly at CT scan, no constitutional symptoms, no cytopenia, normocellular bone marrow. Partial Response (PR) is a reduction \> 50% in lymphocytes, lymphadenopathy, spleen or liver, no cytopenia. PD if appearance of any new lesion, or increase in lymphocytes \> 50%, or occurrence of cytopenia attributable to CLL.

Time frame: CR assessed 52 weeks after the beginning of combination treatment

Population: Efficacy population: 21 patients who received at least one dose of monalizumab. According to the protocol, patients who discontinued treatment due to disease progression before the end of 8 weeks were replaced. Of note,1 patient (grade 3 hemolytic anemia due to disease progression at W4) was replaced and was then excluded from efficacy population.

Measure of best overall response at any time during the study. cCR: confirmed complete response/remission; uCR: unconfirmed complete response / remission; PR: partial response/remission; SD: stable disease; PD: progressive disease. Per International Workshop on Chronic Lymphocytic Leukemia (IWCLL), Complete Response (CR) is defined as lymphocytes \<4x109/l, absence of lymphadenopathy, hepatomegaly and splenomegaly at CT scan, no constitutional symptoms, no cytopenia, normocellular bone marrow. Partial Response (PR) is a reduction \> 50% in lymphocytes, lymphadenopathy, spleen or liver, no cytopenia. PD if appearance of any new lesion, or increase in lymphocytes \> 50%, or occurrence of cytopenia attributable to CLL. In order to have a confirmed CR (cCR), the CR must be confirmed by a scan and a bone marrow assessment assessed at least 2 months after the first occurrence of CR. Otherwise it would be an unconfirmed CR (uCR).

Time frame: From beginning of study drug treatment to the end of study (up to 24 months)

Population: Efficacy population: 21 patients who received at least one dose of monalizumab. According to the protocol, patients who discontinued treatment due to disease progression before the end of 8 weeks were replaced. Of note,1 patient (grade 3 hemolytic anemia due to disease progression at W4) was replaced and was then excluded from efficacy population.

The duration of remission (DOR) is defined as the time from the date of first evaluation of the remission (cCR, uCR or PR) to the first documentation of progressive disease, relapsed disease or death. In case an assessment of progressive / relapsed disease or death does not exist, the DOR was censored at the time of the last disease assessment date. The DOR was calculated only for the patients with a remission that was assessed at 52 weeks.

Time frame: Up to 24 months

Population: 21 patients evaluated for efficacy. 1 patient treated at 4 mg/kg was withdrawn due to grade 3 hemolytic anemia attribuated to disease progression at W4 and considered as not evaluable for efficacy. Due to the small size of the trial no subgroup analyses have been conducted.

The overall survival (OS) is defined as the time from first dose administration until death from any cause. Alive patients were censored at the most recent date they were known to be alive. Subjects with no assessment post-Baseline were censored at the day of the first dose administration.

Time frame: Up to 24 months.

Population: 22 patients were included in the ITT / Safety population

The Progression Free Survival (PFS) is defined as the time from first dose administration until the occurrence of progressive disease, relapsed disease or death from any cause. Patients without an event at the time of the analyse were censored at his or her last disease assessment date. Patients with no post-Baseline assessment were censored at the day of the first dose administration.

Time frame: Up to 24 months

Population: All 22 enrolled patients were included in the ITT / Safety population