UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
WASHINGTON, D.C. 20549
FORM
CURRENT REPORT
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Item 7.01. Regulation FD Disclosures.
On October 14, 2020, Xencor ("the Company") learned that abstracts accepted for presentation at the upcoming 35th Annual Meeting of the Society for Immunotherapy of Cancer were made publicly available on the meeting's website in error for a period of time prior to their intended release on November 9, 2020. During this time, investors and other interested parties may have accessed and downloaded content, including an abstract submitted by the Company. Abstract 648 submitted by the Company contains updated clinical results from the ongoing Phase 1 dose-escalation and expansion study of XmAb®20717 in patients with advanced solid tumors, current as of the July 8, 2020 data cut-off for submission of the abstract. The abstract is attached hereto as Exhibit 99.1 and is incorporated herein by reference.
The information herein and in the exhibit hereto is being furnished and shall not be deemed to be “filed” for purposes of Section 18 of the Securities Exchange Act of 1934, as amended (the “Exchange Act”), or otherwise subject to the liability of that section, nor shall such information be deemed incorporated by reference in any filing under the Securities Act of 1933, as amended, or the Exchange Act, except as expressly set forth by specific reference in such a filing.
Item 9.01 Financial Statements and Exhibits.
(d) Exhibits.
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99.1 |
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104 | Cover Page Interactive Data File (formatted as inline XBRL). |
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SIGNATURES
Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned hereunto duly authorized.
Date: October 14, 2020 |
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| By: | /s/ Celia Eckert |
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| Celia Eckert |
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| General Counsel & Corporate Secretary |
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Exhibit 99.1
Preliminary safety, pharmacokinetics/pharmacodynamics, and antitumor activity of XmAb20717, a PD-1 x CTLA-4 bispecific antibody, in patients with advanced solid tumors
Background
XmAb20717 is a humanized bispecific monoclonal antibody that simultaneously targets PD-1 and CTLA-4. We report preliminary data from an ongoing, multicenter, Phase 1 study investigating the safety/tolerability, pharmacokinetics/pharmacodynamics, and clinical activity (RECIST 1.1) of XmAb20717 in patients with selected advanced solid tumors.
Methods
A 3+3 dose-escalation design was used to establish a maximum tolerated (MTD)/recommended dose for evaluation in parallel expansion cohorts, including melanoma, renal cell carcinoma, non-small cell lung cancer (NSCLC), prostate cancer, and a basket of tumor types without an FDA-approved checkpoint inhibitor (CI; n≤20 each). XmAb20717 was administered as an infusion on Days 1 and 15 of each 28-day cycle.
Results
As of 08Jul2020, 109 patients had been treated (Table 1), and 30 were continuing treatment. In escalation, 6 dose levels (0.15-10.0 mg/kg) were evaluated (n=34); an MTD was not established. Expansion cohorts were initiated at 10 mg/kg (n=72), and a 15 mg/kg escalation cohort was added (n=3). T-cell proliferation was noted in peripheral blood at doses as low as 3 mg/kg and was highest at 10 mg/kg. At this dose, consistent proliferation of CD8+ and CD4+ T cells was observed, indicative of dual PD-1 and CTLA-4 checkpoint blockade (Figure 1). Paired pre- and post-dosing biopsies showed increased intratumoral T-cell infiltration and IFN-response signatures following treatment. Grade 3/4 treatment-related adverse events (TRAEs) reported for ≥3 patients included rash (13%), transaminase elevations (7%), lipase increased (4% [2% with amylase increased]), and acute kidney injury (3%), all considered immune-related. There were 2 Grade 5 TRAEs: immune-mediated pancreatitis (in the presence of pancreatic metastases) and immune-mediated myocarditis (Grade 4) that contributed to respiratory failure. A complete response was reported as the best overall response for 1 patient (melanoma); partial responses were reported for 5 patients (2 melanoma, 2 NSCLC, 1 ovarian). The objective response rate was 13% overall and 21% at 10 mg/kg (6/46 and 6/29 evaluable patients, respectively). All responders had prior CI exposure. Responses were observed only at 10 mg/kg and, within the 10 mg/kg group, appeared to correlate with higher peak serum concentration and area under the curve.
Conclusions
XmAb20717 induced T-cell proliferation in peripheral blood consistent with dual-checkpoint blockade. Preliminary data indicate XmAb20717 was generally well-tolerated and associated with evidence of antitumor activity in CI-pretreated patients with various types of advanced solid tumors.
Trial Registration
NCT03517488
Ethics Approval
The study was approved by each institution’s IRB.
Table 1. Demographics and Baseline Characteristics
Characteristic | Escalation (n = 37) | Expansion Cohorts | ||||
Melanoma (n = 20) | RCC (n = 8) | NSCLC (n = 20) | Prostate (n = 7) | Basket (n = 17) | ||
56 (32-81) | 67 (45-82) | 64 (55-85) | 72 (49-81) | 69 (63-74) | 61 (41-78) | |
Male | 60% | 60% | 75% | 75% | 100% | 24% |
Months since initial diagnosis, median (range) | 43 (3-313) | 58 (6-511) | 74 (52-249) | 38 (8-113) | 85 (1-110) | 30 (1-165) |
Lines of prior systemic therapy, median (range) | 4 (0-9) | 3 (0-9) | 4 (0-6) | 3 (0-9) | 0 (0-11) | 5 (0-8) |
Prior checkpoint inhibitor therapy | 76% | 80% | 63% | 70% | 14% | 35% |
