The preliminary results from patients enrolled in the 1L urothelial cancer cohort in the ongoing PIVOT-02 Phase 1/2 study were shared in a poster presentation today titled, "NKTR-214 + nivolumab in first-line advanced/metastatic urothelial carcinoma (mUC): Updated results from PIVOT-02" by
"Preliminary data from the ongoing PIVOT-02 trial in metastatic urothelial cancer patients demonstrated important response rates, including complete responses, in patients who were cisplatin-ineligible or refused standard of care," said
Highlights from the ASCO-GU presentation in 1L metastatic urothelial carcinoma patients include:
Clinical Efficacy
Response measured per RECIST 1.1 for per protocol efficacy-evaluable patients treated at the recommended Phase 2 dose (RP2D) and with ≥1 post-treatment scan as of
- Best overall response rate (ORR) was 48% (13/27) in efficacy-evaluable patients, with a 19% (5/27) complete response (CR) rate.3
- ORR by immune-related RECIST (irRECIST) was 52% (14/27); ORR in patients with visceral non-nodal metastases was 53% (8/15).
- ORR in patients that refused standard of care was 55% (6/11); in cisplatin-ineligible patients ORR was 44% (7/16).
- Disease control rate (DCR) was 70% (defined as CR + partial response (PR) + stable disease (SD)).
- Median percent reduction in target lesions from baseline in all 27 efficacy-evaluable patients was 32%.
- Median percent reduction in target lesions from baseline in all 13 responders was 78%.
- Median time to response was 2.0 months.
- In patients with RECIST response, no patients discontinued due to relapse.
- Amongst the 23 patients with known pre-treatment programmed death-ligand 1 (PD-L1) status, ORR in PD-L1 negative patients was 45% (5/11) and in PD-L1 positive patients was 50% (6/12).
Clinical Safety
- Treatment was generally well tolerated and the most common (>15%) treatment-related adverse events (TRAEs) were flu-like symptoms4 (71%), fatigue (56%), rash (46%) and pruritus (32%), decreased appetite (27%) and nausea (22%).
- A total of 6/41 (15%) of patients experienced a Grade 3 TRAE, with 4 patients discontinuing due to a TRAE.
- No patients experienced a Grade 4/5 TRAE.
Biomarkers and Mechanism of Action
- 70% (7/10) of patients who were PD-L1 negative at baseline converted to PD-L1 positive by Week 3.
- All patients who were initially PD-L1 positive at baseline remained PD-L1 positive.
- RECIST responses observed were independent of baseline PD-L1 status and CD8+ T cell infiltrate.
- A copy of Dr. Siefker-Radtke's poster presentation of PIVOT-02 data is available on Nektar's corporate website at https://www.nektar.com/download_file/656/0.
The PIVOT-10 study evaluating bempegaldesleukin in combination with nivolumab in 1L locally advanced or metastatic urothelial carcinoma cisplatin-ineligible patients with low PD-L1 expression is currently recruiting patients (NCT03785925).
Analyst Call with Urothelial Cancer Specialist
Nektar will webcast an analyst conference call featuring Dr. Siefker-Radtke today,
About Bempegaldesleukin (NKTR-214)
Bempegaldesleukin is an investigational, first-in-class, CD-122-preferential IL-2 pathway agonist designed to provide rapid activation and proliferation of cancer-killing immune cells, known as CD8+ effector T cells and natural killer (NK) cells, without over activating the immune system. Bempegaldesleukin stimulates these cancer-killing immune cells in the body by targeting CD122 specific receptors found on the surface of these immune cells. CD122, which is also known as the Interleukin-2 receptor beta subunit, is a key signaling receptor that is known to increase proliferation of these effector T cells.5 In clinical and preclinical studies, treatment with bempegaldesleukin resulted in expansion of these cells and mobilization into the tumor micro-environment.6,7 Bempegaldesleukin has an antibody-like dosing regimen similar to the existing checkpoint inhibitor class of approved medicines.
About Nektar
Forward-Looking Statements
This press release contains forward-looking statements which can be identified by words such as: "will," "may," "designed" and similar references to future periods. Examples of forward-looking statements include, among others, statements we make regarding the therapeutic potential bempegaldesleukin in combination with other therapeutic agents, and the availability of results and outcomes from our clinical and preclinical studies. Forward-looking statements are neither historical facts nor assurances of future performance. Instead, they are based only on our current beliefs, expectations and assumptions regarding the future of our business, future plans and strategies, anticipated events and trends, and other future conditions. Because forward-looking statements relate to the future, they are subject to inherent uncertainties, risks and changes in circumstances that are difficult to predict and many of which are outside of our control. Our actual results may differ materially from those indicated in the forward-looking statements. Therefore, you should not rely on any of these forward-looking statements. Important factors that could cause our actual results to differ materially from those indicated in the forward-looking statements include, among others: (i) our statements regarding the therapeutic potential of bempegaldesleukin are based on preclinical and clinical findings and observations to date from ongoing clinical studies; (ii) bempegaldesleukin is in early stage clinical development and the risk of failure remains high and failure can unexpectedly occur at any stage for one or more of the cancer indications being studied prior to regulatory approval due to lack of sufficient efficacy, safety considerations or other factors that negatively impact drug development; (iii) data reported from ongoing clinical trials is necessarily interim data only and the final results will change based on continuing observations from patients that currently remain enrolled in the trials and new observations from patients enrolling in the trials; (iv) scientific discovery of new medical breakthroughs is an inherently uncertain process and the future regulatory approval of potential new drug candidates (such as bempegaldesleukin) is therefore very uncertain and unpredictable; (v) patents may not issue from our patent applications for our drug candidates, patents that have issued may not be enforceable, or additional intellectual property licenses from third parties may be required; and (vi) certain other important risks and uncertainties set forth in Nektar's Quarterly Report on Form 10-Q filed with the
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1 rINN
2 Efficacy-evaluable defined per protocol as patients with at least one post-baseline scan. As of 12/3/2018, one patient was excluded for non-eligibility (no target lesion), and three patients discontinued prior to first scan (one due to patient decision; one due to clinical progression; one due to death from disease); ten patients pending first scan in database.
3 ORR by primary investigator assessment included four unconfirmed responses: two patients with uPR and one patient with uCR pending confirmatory scan and one patient with uPR discontinued for AE after first scan with no confirmatory scan. Since 12/3/2018, three of four patients have had scans confirming responses (including CR).
4 Flu-like symptoms includes preferred terms: chills, influenza, influenza-like illness, pyrexia
5 Boyman, J., et al., Nature Reviews Immunology, 2012, 12, 180-190.
6 Charych, D., et al.,
7 Diab, A., et al.,
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