Expert Discusses Promise of CMB305 Immunotherapy Regimen in Sarcoma


CMB305, an immunotherapy regimen that generates and expands anti–NY-ESO-1 T cells, demonstrated a favorable survival rate compared with other approved agents for recurrent soft tissue sarcoma, according to results presented at the 2017 ASCO Annual Meeting.

Neeta Somaiah, MD

Neeta Somaiah, MD

CMB305, an immunotherapy regimen that generates and expands anti—NY-ESO-1 T cells, demonstrated a favorable survival rate compared with other approved agents for recurrent soft tissue sarcoma, according to results presented at the 2017 ASCO Annual Meeting.

The phase I C131study included 25 patients with either synovial or myxoid/round cell liposarcoma who had previously received treatment for locally advanced or metastatic disease.

“The 12-month overall survival rate [with CMB305] was 83% and 76% of patients are currently alive at 18 months,” said lead author Neeta Somaiah, MD, “The median PFS was 4.7 months and the disease control rate was 64%.”

In an interview withTargeted Oncology, Somaiah, assistant professor, Department of Sarcoma Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, discussed the efficacy of CMB305 in patients with synovial sarcoma or myxoid/round cell liposarcoma, and its potential as a treatment for other soft tissue sarcomas.

TARGETED ONCOLOGY:Can you provide an overview of this study?

Somaiah:C131 is a phase I study of CMB305 for patients with NY-ESO-1—positive recurrent or metastatic soft tissue sarcoma. CMB305 is a prime boost immunotherapeutic therapy that targets the NY-ESO-1 antigen consisting of LV305, which is a dendritic cell targeting the lentiviral vector. It was also coadministered with G305, which is a potent TLR4 agonist that is given along with the entire NY-ESO protein.

This sequential administration leads to a priming of the immune system with LV305 causing CD8 T-cell response, then you come in with a boost with the G305. This leads to an immune response with both T cells and antibodies.

This study was a phase I study with a dose-escalation and a dose-expansion cohort. There were a total of 49 patients included in the safety population, and 25 of those patients had sarcoma. The majority of those sarcoma patients had synovial sarcoma or myxoid/round cell liposarcoma, the subtypes that have maximum NY-ESO-1 expression.

In terms of the subpopulations, we included patients who had relapsed or metastatic soft tissue sarcoma with NY-ESO-1 expression, but they had to have a limited tumor burden given that this approach takes time to kick in to the system. Of these patients, 92% had metastatic disease and 56% had tumor progression at the time of entry into the study. More than 50% had 2 or more lines of prior chemotherapy.

The 12-month overall survival rate was 83% and 76% of patients are currently alive at 18 months. The median PFS was 4.7 months and the disease control rate was 64%.

The patients who were having disease progression at baseline did notice a durable tumor growth arrest. When we look at these patients, several had an induction of immune response against NY-ESO-1.

The exploratory biomarker analyses was interesting because 77% of patients did have induction of immune response, whether it be with T cells or antibodies against NY-ESO-1. Of these patients, 33% had both T cells and antibody responses to this prime boost approach.

In the correlative analysis, we included more of the patients, not just sarcoma. We also did a combined analysis of patients on the LV305 study, which is the previous phase I study. We noted that patients who had an induction of an immune response seem to be the ones who had the overall survival benefit.

TARGETED ONCOLOGY:Could this have any other potential in other sarcoma subtypes?

Somaiah:It absolutely does. We have done previous studies also looking at the NY-ESO expression across many subtypes. There are other subtypes that express NY-ESO-1, however the percentage of those other subtypes generally see around 30% expression, whereas for the subtypes in this study the expression is almost 80% to 100%.

In terms of screening for a small study, it’s easier if you screen patients with synovial or myxoid sarcoma, since you have a high positivity rate. If you chose other sarcoma subtypes or even other cancers, such as lung cancer or ovarian cancer, you need to screen more patients to get NY-ESO-1—positive expression. This is why we focused on these groups in the study but in the future, it should have implications for any other NY-ESO-1–positive tumors.

TARGETED ONCOLOGY:What are some of the biggest outstanding questions?

Somaiah:We see that there is an induction of immune response. Now the key thing we need to determine is, are those immune cells able to get into and ultimately kill the tumor? We know that it takes 3 to 6 months for the immune reaction to occur in the body after treatment, so how do we design a study to get the maximum benefit for these patients?

When selecting patients, we don’t want to take patients who are rapidly progressing and are going to go off the study soon. We need to be able to select the patients who are going to benefit from this durable and delayed induction of immune response.

TARGETED ONCOLOGY:What are the next steps?

Somaiah:Follow-up studies are going to determine if this could get into the market. Also, we want to choose the right patient population. We want to determine if this drug allows patients to delay their progression and live longer, whether they receive it in the maintenance setting, in comparison to another therapy, or in the maintenance setting after first-line chemotherapy.

I don’t think we'll have to focus as much on partial responses with this agent if we are using it as a single agent. However, we are not sure if it can cause more durable tumor growth arrest and improve survival for patients who then might go on to receive other therapies, or if that immune reduction will cause them to live longer.

TARGETED ONCOLOGY:How do you foresee an agent like this changing the treatment landscape?

Somaiah:It can potentially change the landscape for those patients with synovial or myxoid sarcoma who respond well to chemotherapy but ultimately progress. This treatment in those patients with metastatic disease allows them to live longer and can even be used in the adjuvant setting due to the high risk of recurrence. If we can get the immune response kicked in for patients who have these high-risk tumors early on, we might be able to potentially cure them and prevent relapses. That is the hope but it remains to be seen.

TARGETED ONCOLOGY:Is there anything else you would like to add?

Somaiah:The biomarker analysis is very interesting. There was a patient on the initial phase I study who had a partial response 1 year after entering the study and who was still in remission 2 years later.

We studied that patient’s biomarker profile in detail and there seems to be a hint regarding which patients are going to respond. The key is selecting that right patient population who is going to benefit from this.


Nolan E, Vaillant F, Branstetter D, et al. RANK ligand as a potential target for breast cancer prevention in BRCA1-mutation carriers. [Published online June 20, 2016.]Nat Med.doi:10.1038/nm.4118.

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