Marion Carrigan

Purpose The multicohort phase Ib KEYNOTE-028 (NCT02054806) study was designed to evaluate the safety and efficacy of pembrolizumab, an anti-programmed death 1 monoclonal antibody, in patients with programmed death ligand 1 (PD-L1) -positive advanced solid tumors. The results from the advanced endometrial cancer cohort are reported. Patients and Methods Female patients with locally advanced or metastatic PD-L1-positive endometrial cancer who had experienced progression after standard therapy were eligible. Patients received pembrolizumab 10 mg/kg every 2 weeks for up to 24 months or until progression or unacceptable toxicity. Primary efficacy end point was objective response rate by RECIST (version 1.1). Secondary end points included safety, duration of response (DOR), progression-free survival, and overall survival. The data cutoff was February 17, 2016. Results Of 75 patients screened, 36 (48.0%) had PD-L1-positive tumors, and 24 (32.0%) were enrolled. Fifteen (62.5%) of these 24 patients had received at least two previous lines of therapy for advanced disease. Three patients (13.0%) achieved confirmed partial response (95% CI, 2.8% to 33.6%); the median DOR was not reached. Two patients were still receiving treatment and exhibiting continued response at time of data cutoff. Three additional patients (13.0%) achieved stable disease, with a median duration of 24.6 weeks. One patient who achieved partial response had a polymerase E mutation. Thirteen patients (54.2%) experienced treatment-related adverse events (AEs), with fatigue (20.8%), pruritus (16.7%), pyrexia (12.5%), and decreased appetite (12.5%) occurring in ≥ 10% of patients. Grade 3 treatment-related AEs were reported in four patients. No patient experienced a grade 4 AE, and no patient discontinued treatment because of an AE. Conclusion Pembrolizumab demonstrated a favorable safety profile and durable antitumor activity in a subgroup of patients with heavily pretreated advanced PD-L1-positive endometrial cancer.

(Abstracted from J Clin Oncol 2017;35:2535–2541) Endometrial cancer (EC) identified at an early stage is successfully treated in a majority of patients with surgery with or without radiotherapy or chemotherapy. For patients with advanced disease, however, the prognosis is poor; 5-year survival rates are less than 50% in patients with lymph node metastases and less than 20% in those with peritoneal or distant metastases.

5581 Background: There are currently no treatment options for pts with endometrial cancer who progress on chemotherapy. Pembrolizumab is an anti–PD-1 antibody that blocks interaction between PD-1 and its ligands, PD-L1/PD-L2. The safety and efficacy of pembrolizumab were evaluated in advanced solid tumors in the KEYNOTE-028 study (NCT02054806). Preliminary results from the endometrial carcinoma cohort are presented. Methods: Key inclusion criteria were advanced endometrial carcinoma (excluded sarcomas, mesenchymal tumors), failure of prior systemic therapy, ECOG PS 0-1, and PD-L1 expression in ≥ 1% of tumor or stroma cells by IHC. Pembrolizumab 10 mg/kg every 2 wk was given for up to 24 mo or until confirmed progression, intolerable toxicity, death, or consent withdrawal. Response was assessed every 8 wk for the first 6 mo and every 12 wk thereafter. The primary end point was ORR per RECIST v1.1 by investigator assessment. Results: In the 24 pts enrolled, median age was 67.0 y; 66.7% had an ECOG PS of 1; 62.4% received ≥ 2 prior therapies for metastatic disease. As of Dec 10, 2015, median follow-up duration was 69.9 wk (range, 5.4-84.4). Treatment-related AEs (TRAEs) occurred in 13 (54.2%) pts; most common were pruritus (n = 4, 16.7%), asthenia, fatigue, pyrexia, and decreased appetite (n = 3 each; 12.5%). Three pts experienced grade 3 TRAEs: 1 pt had back pain and asthenia (both resolved), 1 pt had diarrhea (resolved), 1 pt had asthenia, anemia, hyperglycemia, and hyponatremia (all unresolved). No pts died or discontinued pembrolizumab because of a TRAE. ORR (confirmed) was 13.0% (PR, n = 3; 95% CI, 2.8-33.6); median duration of response was not yet reached (range, 40.3+ to 65.1+ wk). Three pts achieved stable disease (13%; 95% CI, 2.8-33.6; median duration, 24.6 wk [range, 13.1-24.6]). Six-mo PFS and OS rates were 19.0% and 68.8%, respectively. At data cutoff, all 3 pts with PRs remained on treatment. Conclusions: Pembrolizumab demonstrated an acceptable safety profile and preliminary antitumor activity in heavily pretreated PD-L1+ advanced endometrial cancer pts. The clinical benefit of pembrolizumab for advanced endometrial cancer is being further investigated in the phase 2 KEYNOTE-158 trial (NCT02628067). Clinical trial information: NCT02054806.

Abstract Abstract 3425 Poster Board III-313 MDX-1342 is a fully human monoclonal antibody (HuMAb) with enhanced antibody-dependent cellular cytotoxicity (ADCC) effector function, targeting CD19-membrane receptor which is highly expressed on malignant chronic lymphocytic leukemia (CLL) cells. An open-label, multi-center, multiple-dose, dose-escalating Phase 1 study is being conducted to determine the safety and tolerability profile of MDX-1342 in subjects with CD19-positive relapsed or refractory CLL. To date, MDX-1342 has been administered intravenously (iv) weekly for 4 weeks to 12 subjects (8 Male, 4 Female) - in cohorts of 3 subjects each - at doses of 0.7, 7, 40, and 200 mg/dose. Overall, MDX-1342 has been well tolerated. No drug-related serious adverse events have been reported among the 12 subjects treated. Grade 1 and 2 infusion reactions (including rigors, chills, and wheezing) have been observed in 9 subjects. This has been adequately managed with the use of antihistamines and corticosteroids. Dose escalation continues and a maximum tolerated dose has not yet been identified. Of the 9 currently evaluable subjects, 1 has experienced a partial response (40 mg/dose cohort), 6 have stable disease and 2 have discontinued due to progressive disease. Preliminary results indicate antileukemic signals with dose-correlative reductions in both white blood counts (WBC) and circulating CD20+ cells after one 4-week cycle of weekly i.v. infusions of MDX-1342. In the 40 mg/dose cohort, the median reduction in WBC was 62% and the median reduction in circulating CD20+ cells was 74%. Additional subjects are being accrued to higher dose cohorts to more accurately characterize the safety and clinical activity of MDX-1342 and to determine if there is a consistent cumulative drop in WBC and circulating CD20+ cells as the dose increases. Disclosures Assad: Medarex, Inc.: Employment. Carrigan:Medarex, Inc: Employment.