Activity of RX-3117, an oral antimetabolite nucleoside, in patients with pancreatic cancer: Preliminary results of stage 1 of the phase 1a/2b

445 Background: RX-3117 is an oral smallmolecule antimetabolite, cyclopentyl pyrimidyl nucleoside that is activated by uridine cytidine kinase 2. RX-3117 has shown efficacy in xenograft models of gemcitabine resistant pancreatic, bladder and colorectal cancer. Data from stage 1 of the Phase 1b/2a clinical study of RX3117 as a single agent in subjects with metastatic pancreatic cancer is described below. Methods: Stage 1 of the Phase 1b/2a study (NCT02030067) is designed to evaluate safety, tolerability and efficacy following treatment with 700 mg administered orally once-daily for 5 consecutive days with 2 days off per week for 3 weeks with 1 week off in each 4 week cycle in a 2-stage Simon design. Eligible subjects (aged ≥ 18 years) were those with relapsed/refractory metastatic pancreatic cancer. The primary endpoint is a ≥ 20% (2 out of 10 subjects) rate of progression free survival (PFS) benefit (i.e., proportion of subjects with stable disease for at least 4 months) and/or a 10% (1 of 10 subjects) with a partial response rate or better. Results: As of Sep 2016, 8 out of 10 subjects have been enrolled (4 females, 4 males), the mean age was 70 years, ECOG performance status was 1 and 5 subjects had received more than 4 prior therapies. Two subjects met the primary endpoint of stable disease with a duration of 140-168 days at the time of this submission. The most frequent adverse events were moderate to severe anemia, mild to moderate fatigue, abdominal pain and diarrhea. Conclusions: This ongoing trial shows an early efficacy signal where RX-3117 is active against advanced pancreatic cancer. As the primary endpoint has been achieved, the study will now move to stage 2 where an additional 40 subjects with advanced pancreatic cancer will be enrolled. Clinical trial information: NCT02030067

Looking Beyond Surveillance, Epidemiology, and End Results: Patterns of Chemotherapy Administration for Advanced Non-small Cell Lung Cancer in a Contemporary, Diverse Population

Introduction:Chemotherapy prolongs survival without substantially impairing quality of life for medically fit patients with advanced non-small cell lung cancer (NSCLC), but population-based studies have shown that only 20 to 30% of these patients receive chemotherapy. These earlier studies have relied on Medicare-linked Surveillance, Epidemiology, and End Results (SEER) data, thus excluding the 30 to 35% of lung cancer patients younger than 65 years. Therefore, we determined the use of chemotherapy in a contemporary, diverse NSCLC population encompassing all patient ages.Methods:We performed a retrospective analysis of patients diagnosed with stage IV NSCLC from 2000 to 2007 at the University of Texas Southwestern Medical Center. Demographic, treatment, and outcome data were obtained from hospital tumor registries. The association between these variables was assessed using univariate analysis and multivariate logistic regression.Results:In all, 718 patients met criteria for analysis. Mean age was 60 years, 58% were men, and 45% were white. Three hundred fifty-three patients (49%) received chemotherapy. In univariate analysis, receipt of chemotherapy was associated with age (53% of patients younger than 65 years versus 41% of patients aged 65 years and older; p = 0.003) and insurance type (p < 0.001). In a multivariate model, age and insurance type remained associated with receipt of chemotherapy. For individuals receiving chemotherapy, median survival was 9.2 months, compared with 2.3 months for untreated patients (p < 0.001).Conclusions:In a contemporary population representing the full age range of patients with advanced NSCLC, chemotherapy was administered to approximately half of all patients—more than twice the rate reported in some earlier studies. Patient age and insurance type are associated with receipt of chemotherapy

A Phase I Dose-Escalation and Dose-Expansion Study of FCN-437c, a Novel CDK4/6 Inhibitor, in Patients with Advanced Solid Tumors

A phase I study evaluated the safety, tolerability, and maximum-tolerated dose (MTD)/recommended phase II dose (RP2D) of FCN-437c, a novel, orally available cyclin-dependent kinase inhibitor (CDK4/6i), in participants with advanced/metastatic solid tumors (aSTs). FCN-437c was escalated from 50 mg (once daily [QD] on days 1&ndash;21 of 28-day cycles) to the MTD/RP2D. In the dose-expansion phase, patients with CDK4/6i-treated breast cancer, or KRAS-mutant (KRASmut) non-small-cell lung cancer (NSCLC) received the MTD. Twenty-two patients were enrolled. The most common tumors in the dose-escalation phase (n = 15) were breast, colorectal, and lung (each n = 4 [27.3%]). The dose-expansion phase included five (71.4%) patients with breast cancer and two (28.6%) with KRASmut NSCLC. Twenty (90.9%) participants experienced FCN-437c&ndash;related adverse events. Dose-limiting toxicities occurred in two (33.3%) participants (200-mg dose, dose-escalation phase): grade 3 neutropenia and grade 4 neutrophil count decreased. Due to toxicities reported at 150 mg QD, the MTD was de-escalated to 100 mg QD. One (4.5%) participant (KRASmut NSCLC, 100-mg dose) achieved a partial response lasting 724+ days, and five (22.7%) had stable disease lasting 56+ days. In conclusion, FCN-437c was well tolerated with encouraging signs of antitumor activity and disease control. Further exploration of FCN-437c in aSTs is warranted

RX 3117: Activity of an oral antimetabolite nucleoside in subjects with pancreatic cancer–Preliminary results of stage II of the phase Ia/IIb study

396 Background: RX-3117 is an oral small-molecule antimetabolite, cyclopentyl pyrimidyl nucleoside that is activated by uridine cytidine kinase 2. RX-3117 has shown efficacy in xenograft models of gemcitabine resistant pancreatic, bladder and colorectal cancer. Data from stage 2 of the Phase 1b/2a clinical study of RX3117 as a single agent in subjects with metastatic pancreatic cancer is described below. Methods: Stage 2 of the Phase 1b/2a study (NCT02030067) is designed to evaluate safety, tolerability and efficacy following treatment with 700 mg administered orally once-daily for 5 consecutive days with 2 days off per week for 3 weeks with 1 week off in each 4 week cycle. Eligible subjects (aged ≥ 18 years) had relapsed/refractory metastatic pancreatic cancer. The primary endpoint is a ≥ 20% rate of progression free survival (PFS) benefit (i.e., proportion of subjects with stable disease for at least 4 months) and/or a 10% of evaluable subjects with a partial response rate or better. Results: As of Sep 2017, 44 subjects have been enrolled (22 females, 22 males). The median age was 68 years, ECOG performance statuses were 0 (13 subjects) and 1 (31 subjects) and 6 subjects had received 4 or more prior therapies. One subject had an unconfirmed partial response and 21 subjects met the primary endpoint of stable disease with a duration of 30-224 days. The most frequent adverse events were mild to moderate anemia (19%), mild to moderate fatigue (15%), mild to moderate diarrhea (11%), and severe anemia (9%). Conclusions: This ongoing trial shows an early efficacy signal where RX-3117 is active against advanced pancreatic cancer. The study continues to enroll subjects with advanced pancreatic cancer into stage 2. A phase 2 study with nab-paclitaxel in first-line patients with advanced pancreatic cancer has been started. Clinical trial information: NCT02030067