CC-122 Plus Obinutuzumab Effective in Relapsed/Refractory B-Cell NHL

Combining the anti-CD20 monoclonal antibody obinutuzumab with the first-in-class pleiotropic pathway modifier CC-122 led to high response rates and durable remissions in patients with relapsed/refractory B-cell non-Hodgkin lymphoma (NHL), according to results from a phase Ib study presented at the 22nd Congress of the European Hematology Association.

CC-122 has immunomodulatory effects on T-cell and natural killer-cell function, which could result in “potent anti-lymphoma effects,” study co-author and presenter Réda Bouabdallah, MD, of the Institut Paoli-Calmettes in Marseille, France, explained.

In this multicenter, open-label, dose-escalation and dose-expansion study, researchers enrolled 38 patients (median age = 60 years; range = 26-81 years) with three subtypes of B-cell NHL: diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL) or marginal zone lymphoma (MZL; n=19).

Patients were eligible for inclusion if they had received one or more prior regimens for CD20-positive NHL, FL, or MZL, or two or more prior regimens and/or autologous hematopoietic cell transplantation (AHCT) for DLBCL.

Patients received oral CC-122 in escalating doses (administered on days 1-5), in combination with intravenous obinutuzumab 1,000 mg (administered on days 2, 8, and 15 of cycle 1 and on day 1 of cycles 2-8), until disease progression or unacceptable toxicity.

At baseline, 21 percent of patients had bone marrow involvement with lymphoma. The median number of prior therapies was four (range = 1-12 therapies), and 14 patients (37%) had undergone AHCT.

Patients received CC-122 for a median of 22 weeks (range = 3-71 weeks), which is equivalent to 6 cycles (range = 1-18 cycles). The overall response rate  (ORR) was 66 percent, including a complete response rate of 32 percent (n=12) and a partial response rate of 34 percent (n=13; TABLE). Patients with FL or MZL appeared to have the highest ORR at 84 percent, compared with an ORR of 47 percent for patients with DLBCL (p value not provided).

The median time to best response was 57 days (range = 56-114 days), and the median duration of response was not yet reached.

In the dose-escalation trial, two patients (5%) discontinued treatment because of adverse events (AEs) and two patients (5%) experienced a dose-limiting toxicity. Ten patients (29%) required a dose reduction of CC-122, and 26 patients (76%) required a temporary interruption of treatment – primarily related to AEs. For most patients (56%), the treatment interruption was shorter than 1 week.

Sixty-five percent of patients experienced AEs. The most common (≥10%) grade 3/4 AEs were neutropenia (50%) and thrombocytopenia (21%). Fifteen patients (44%) had one or more serious AEs, including two cases of febrile neutropenia (related to CC-122), two cases of cytokine release syndrome (related to obinutuzumab), and two cases of pneumonia. Three patients died during the study (2 from progressive disease; 1 related to AEs).

The results of this early study are limited by the small sample size and the lack of a comparator arm. Dr. Bouabdallah noted that, at the time of presentation, “the 30 patients receiving CC-122 at a dose of 3 mg and higher have shown the best and most durable response,” and 3 mg is being used as the recommended dose for a phase II trial of CC-122 plus obinutuzumab.

The authors report no relevant conflicts of interest.


Michot JM, Bouabdallah R, Doorduijn JK, et al. CC-122 in combination obinutuzumab: a phase 1b study to relapsed or refractory patients with diffuse large B-cell lymphoma, follicular lymphoma, or marginal zone lymphoma. Abstract #S467. Presented at the 22nd Congress of the European Hematology Association, June 24, 2017; Madrid, Spain.

TABLE. Efficacy by NHL Type

All patients (N=38)

DLBCL (n=19)

FL/MZL (n=19)

Overall response

25 (66%)

9 (47%)

16 (84%)

Complete response

12 (32%)

3 (16%)

9 (47%)

Partial response

13 (34%)

6 (32%)

7 (37%)

Stable disease

4 (11%)

3 (16%)

1 (5%)

Progressive disease

6 (16%)

4 (21%)

2 (11%)

Not evaluable

3 (8%)

3 (16%)


DLBCL = diffuse large B-cell lymphoma; FL = follicular lymphoma; MZL = marginal zone lymphoma