Funda Meric-Bernstam, MD

Funda Meric-Bernstam, MD, chair of the Department of Investigational Cancer Therapeutics, medical director of the Institute for Personalized Cancer Therapy, and a professor in the Divisions of Cancer Medicine and Surgery at The University of Texas MD Anderson Cancer Center, discusses the activity of the combination of telaglenastat (CB-839) and cabozantinib (Cabometyx) in heavily pretreated patients with metastatic renal cell carcinoma (mRCC).

Overall, the combination of telaglenastat and cabozantinib was well tolerated, says Meric-Bernstam. The recommended phase II dose of telaglenastat was 800 mg twice daily, which is the same as the recommended dose for the monotherapy. The adverse event profile was in line with what has been seen with cabozantinib alone. Notably, preliminary efficacy with the regimen was promising, she adds. Among 12 of 13 evaluable patients, 2 had papillary carcinoma. In the overall population, the objective response rate (ORR) was 42%. In the 10 patients with clear cell RCC, the ORR was 50% with the regimen.

In terms of response trends, investigators noted some deep responses in patients who were heavily pretreated. Regarding the duration of response, 5 patients received 14 months of treatment or more. At the time of data cut-off, 3 patients were still on treatment. The time to treatment response was more varied; some patients had early responses to the treatment, whereas others had delayed responses. This underscores the need for further follow-up, concludes Meric-Bernstam.

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Dr. Meric-Bernstam on the Activity of Telaglenastat and Cabozantinib in mRCC

Funda Meric-Bernstam, MD, chair, Department of Investigational Cancer Therapeutics, medical director, Institute for Personalized Cancer Therapy, professor of medicine, The University of Texas MD Anderson Cancer Center, discusses preliminary data with a novel combination in renal cell carcinoma (RCC).

In a phase I study presented at the 2019 Genitourinary Cancers Symposium, the glutaminase inhibitor CB-839 was combined with the VEGF TKI cabozantinib (Cabometyx). Meric-Bernstam says that preliminary efficacy looks promising and that the combination had a similar toxicity profile to cabozantinib alone.

Of the 13 patients enrolled in the study, 12 were evaluable for response. Objective response rate (ORR) in the general population of patients with RCC was 42%. Of the 10 patients with clear-cell RCC, the ORR was 50%. Moreover, the combination led to durable responses in a heavily pretreated patient population, Meric-Bernstam adds. Five patients remained on therapy for 14 months or longer, and 3 patients remained on treatment at the time of data cut-off. Notably, some patients demonstrated delayed response, so longer-term follow-up will paint a clearer picture of the durability of these responses, says Meric-Bernstam.

Funda Meric-Bernstam, MD, chair, Department of Investigational Cancer Therapeutics, medical director, Institute for Personalized Cancer Therapy, professor of medicine, The University of Texas MD Anderson Cancer Center, discussed preliminary data with a novel combination in the treatment of patients with renal cell carcinoma.

Dr. Meric-Bernstam Discusses Novel Combination in RCC

Funda Meric-Bernstam, MD, chair, Department of Investigational Cancer Therapeutics, medical director, Institute for Personalized Cancer Therapy, professor of medicine, The University of Texas MD Anderson Cancer Center, discusses the combination of CB-839 plus cabozantinib (Cabometyx) in patients with renal cell carcinoma (RCC).

Cancer cell metabolism is increasingly becoming acknowledged as an important therapeutic target. Glutamine and glucose are key nutrients, while glutaminase converts glutamine into glutamate, enhancing its utilization. The fact that glutaminase is expressed at high levels in RCC supports the rationale for combining the glutaminase inhibitor CB-839 with a VEGF TKI. In vivo, anti-tumor activity is increased with this combination, Meric-Bernstam says.

A phase I study looking at this combination was presented at the 2019 Genitourinary Cancers Symposium. Cabozantinib was given at 60 mg per day, while CB-839 was administered twice daily at 600 mg or 800 mg. In the study of 13 patients with RCC, 11 had clear cell disease and 2 had papillary disease. Overall, the combination appeared to be well tolerated, with the recommended dose of CB-839 being 800 mg twice daily—the same as the monotherapy’s recommended dose.


Funda Meric-Bernstam, MD, chair, Department of Investigational Cancer Therapeutics, medical director, Institute for Personalized Cancer Therapy, professor of medicine, The University of Texas MD Anderson Cancer Center, discusses the combination of CB-839 plus cabozantinib in patients with renal cell carcinoma.

Funda Meric-Bernstam, MD

Articles

Dr. Meric-Bernstam on the Activity of Telaglenastat and Cabozantinib in mRCC

Dr. Meric-Bernstam Discusses Novel Combination in RCC

Dr. Meric-Bernstam on CB-839 Plus Cabozantinib in RCC