Early-stage trial shows promising results for Opdivo, bempegaldesleukin combination in first-line urothelial carcinoma

Updated preliminary results from a Phase I/II trial evaluating the combination of Bristol-Myers Squibb's immunotherapy Opdivo (nivolumab) plus Nektar Therapeutics' bempegaldesleukin showed signs of tumour reduction in patients with first-line advanced or metastatic urothelial carcinoma, the latter company announced Friday. Mary Tagliaferri, chief medical officer at Nektar, said findings from the ongoing PIVOT-02 trial demonstrated "important response rates, including complete responses, in patients who were cisplatin-ineligible or refused standard of care." She added that "these responses were observed regardless of baseline PD-L1 expression and no relapses occurred." 

In February last year, Bristol-Myers Squibb agreed to pay $1 billion upfront to develop bempegaldesleukin, also known as NKTR-214, in combination with Opdivo and Yervoy (ipilimumab) across multiple tumour types. In addition to urothelial carcinoma, PIVOT-02 is also evaluating the combined therapy in melanoma, renal cell carcinoma, non-small-cell lung cancer or triple-negative breast cancer. 

The latest results, presented at the American Society of Clinical Oncology Genitourinary Cancers Symposium (ASCO-GU) for the cohort of stage IV bladder cancer patients, showed that the best overall response rate (ORR) for the combination was 48 percent among 27 efficacy-evaluable patients, with 19 percent of these achieving a complete response. Further, ORR in the 11 patients that refused standard of care was 55 percent, and was 44 percent among the 16 patients who were not eligible for cisplatin. 

The latest findings are an update to data presented at ASCO last year from 10 patients in the bladder cancer cohort, where the ORR was 60 percent (see ViewPoints: Nektar's bladder cancer update looks familiar to sceptics for additional analysis). 

In other results reported Friday, Nektar said median percent reduction in target lesions from baseline in all 27 efficacy-evaluable patients was 32 percent, while median percent reduction in target lesions from baseline in all 13 responders was 78 percent. The company also reported that the median time to response was two months. 

Tagliaferri noted that the combination therapy was "generally well tolerated with no grade 4 or 5 adverse events reported" in the bladder cancer cohort. "Of note, our translational research demonstrated that in patients with the highest unmet medical need, those whose tumours did not express PD-L1 at their baseline scan, treatment with the combination resulted in 70 percent of patients converting to PD-L1-positive expressors," she added. Tagliaferri also indicated that the data "support our development strategy in this tumour setting, including the Phase II PIVOT-10 study underway in cisplatin-ineligible urothelial cancer patients with low PD-L1 tumour expression." 

In November, Bristol-Myers Squibb and Nektar presented data from PIVOT-02 showing an ORR of 53 percent for Opdivo plus bempegaldesleukin in patients with previously untreated melanoma. For related analysis, see ViewPoints: Nektar's IO combo levels out at SITC

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