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This is the last available data - new updates will be tomorrow morning.. It reads very well to me, but I'm a med dimwit:
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Background: RX-3117 is an oral small molecule antimetabolite that is activated by uridine
cytidine kinase 2 (UCK2) which is predominantly expressed in cancer cells. RX-3117 has
demonstrated safety and efficacy in a phase 1b/2a single agent clinical study in previously
treated patients with met-PC or advanced bladder cancer. RX-3117 in combination with nabpac is being evaluated for the 1st line treatment of met-PC cancer.
Methods: This study (NCT03189914) is a multicenter, open label, single arm study, conducted
in 2 phases. Eligible subjects (aged ≥ 18 years) have histologically or radiologically proven
met-PC with no prior therapies for metastatic disease, ECOG PS 0-1, and normal organ
function (hematologic, renal, and liver). Subjects receive the MTD of single agent RX-3117,
(Adashek, J, (2018) JCO; 36:4543 (abstr)) (700 mg administered orally once-daily for 5
consecutive days with 2 days off per week) and standard nab-pac (125 mg/m2 administered IV
once weekly) for 3 weeks with 1 week off per 4-week cycle in a dose de-escalation design.
The primary endpoints of Phase 1 are the safety of the combination in met-PC and to
determine the target Phase 2 dose. The primary endpoint of Phase 2 is PFS and/or objective
clinical response.

Results: As of August 30, 2018, 8 Phase 1 subjects and 13 Phase 2 subjects were enrolled
and treated (9 males and 12 females, median age 67 years). The target Phase 2 dose was
700 mg RX-3117 administered orally once-daily for 5 consecutive days with 2 days off per
week) and nab-pac (125 mg/m2 administered once weekly) for 3 weeks with 1 week off per 4-
week cycle. The most common (≥20%) adverse events were diarrhea, nausea, fatigue,
alopecia, anorexia, and rash. No DLTs were reported. Eleven subjects had at least one onstudy scan (after 2 cycles). One subject experienced a complete response (CR) after 6 cycles
of therapy with normalization of CA19.9 (-76%).Three subjects exhibited a partial response
(PR): two after 2 cycles (39-47%) and one after 4 cycles of therapy (36%). Five subjects
experienced stable disease for at least 2 cycles with tumor marker reductions of 43 – 69%. In
evaluable patients the disease control rate (CR+PR+SD) was 82%. Overall response rate
(CR+PR) was 36%.
Conclusions: RX-3117 in combination with nab-pac at the target dose appear to be safe and
well-tolerated in patients with met-PC. Early anti-tumor activity is seen. Phase 2 of the clinical
study is ongoing.
• The combination of RX-3117 and nab-pac appears safe and well tolerated when
administered at the recommended Phase 2 dose of RX-3117: 700 mg for 5 consecutive
days with 2 days off for 4 weeks and nab-pac at 125mg/m2 in each 4 week cycle in
combination with nab-Pac
• The Phase 2- Stage 1 endpoint was met since 2 (out of 7) subjects had partial
responses thus meeting the protocol defined response criteria..
• The study continues to enroll patients with metastatic pancreatic cancer in Stage 2.
Conclusions
Study Design
Introduction
The current National Comprehensive Cancer Network recommendations suggest
acceptable chemotherapy combinations for met-PC patients include FOLFIRINOX,
gemcitabine plus nab-paclitaxel (nab-pac), and gemcitabine plus erlotinib. However, clinical
trials are also recommended due to the lack of efficacy and severe toxicity (FOLFIRINOX)
with these treatments. RX-3117, an oral small molecule antimetabolite, is phosphorylated by
uridine-cytidine kinase 2 (UCK2), an enzyme found in cancer cells, but relatively absent in
normal cells, allowing a targeted approach. The targeted approach may allow for maximum
dosing of RX-3117 and agents used in combination, such as nab-pac, without compromising
safety. Additionally, RX-3117 is inactivated by cytidine deaminase at a slow rate, allowing
higher cellular concentrations and an increased likelihood of antitumor activity at the
appropriate stage of the cell cycle. Efficacy and safety of RX-3117 as a single agent in
metastatic pancreatic cancer has been previously reported (Adashek, J, (2018) JCO;
36:4543 (abstr).
A B
This is a multicenter, open-label, 2-stage Phase 1b/2a study. Phase 1 was a dose-finding,
open-label study of oral RX-3117 administered in combination with nab-pac to subjects with
newly diagnosed met-PC. The recommended phase 2 dose (RP2D) of RX-3117, in
combination with nab-pac, was determined by the safety profile and dose modification to be
700 mg administered orally once-daily for 5 consecutive days with 2 days off per week and nabpac 125 mg/m2 administered IV once weekly for 3 weeks with 1 week off per 4-week cycle. After
completion of the Phase 1 portion, the Phase 2 study began using a 2 stage, open-label
design, of RX-3117 and nab-pac in combination to treat subjects with met-PC as first line
therapy. In the Stage 1 approximately 10 subjects participated at the dose identified in the
Phase 1 (RP2D). Subjects will be treated for up to 8 cycles of combined therapy. The
protocol provided for an interim analysis to be performed after the first 10 evaluable subjects
in Stage 1 were treated for a minimum of 4 cycles. However, since two PRs were already
achieved in the first seven subjects, the study met the criteria for proceeding to Stage 2.
Approximately 30 additional evaluable subjects will be enrolled to participate in Stage 2
(dose expansion). Subjects will be treated for up to 8 cycles of combined therapy.
• As of 19 September 2018, in the response evaluable population (14 subjects)
from the Phase 1 and Stage 1 of the Phase 2:
• Overall response rate was 29%
• 1 CR was observed after 6 cycles of therapy and confirmed after 8
cycles of therapy (see Fig. A and B below)
• 2 PRs were observed after 2 cycles of therapy, 1 PR was observed
after 4 cycles of therapy
• Disease control rate was 86% (1 Complete Response/ 3 Partial Response/ 8
Stable Disease)
• 12 subjects had stable disease or better for at least 2 cycles (2 months)
• Most subjects with CA 19-9 results exhibited reductions after 1 cycle of
therapy (-32% to -59%). One subject experienced a 46% increase but had
stable disease after 2 cycles.
B
Demographics
Gender n (%) Age Median (Range)
Male 9 (47.4%)
67 (45-81)
Female 10 (52.6%)
Race n (%) ECOG n (%)
White 18 (94.7%) 0 8 (42.1%)
Black or African American 1 (5.3%) 1 11 (57.9%)
Safety
• 8 subjects were treated and 6 were evaluable in Phase 1. No DLTs occurred.
• Most Treatment Emergent Adverse Events (TEAEs) considered related to RX-3117, nabpac, or the combination were mild to moderate (82%). The most common mild to moderate
TEAEs related to RX-3117, nab-pac, or the combination were nausea, diarrhea, fatigue,
alopecia, decreased appetite, rash, pruritus, pyrexia, and vomiting.
Results
CR: Complete Response, ET/EOT: End of Treatment or End of Trial Visit; PD: Progressive Disease, PR: Partial
Response, SD: Stable Disease
TEAE Unrelated nab-pac RX-3117 Both Total n (%)
Decreased appetite 0 1 0 2 3 (15.8%)
Diarrhea 0 0 0 3 3 (15.8%)
Fatigue 0 0 0 3 3 (15.8%)
Anemia 1 0 0 1 2 (10.5%)
Dehydration 0 1 0 1 2 (10.5%)
Febrile neutropenia 0 2 0 0 2 (10.5%)
Nausea 0 0 0 2 2 (10.5%)
Neutropenia 1 0 0 1 2 (10.5%)
Urinary tract infection 1 0 0 1 2 (10.5%)
White blood cell count decreased 0 1 0 1 2 (10.5%)
Grade 3-4 Adverse Events by Relationship
Note: 13 subjects had at least one post-treatment scan and were response evaluable. Two
(out of 7) Phase 2 – Stage 1 subjects had partial responses. Three subjects discontinued
prior to the first on-study scan, and 3 subjects are currently on treatment but have not
completed the first on-study imaging assessment. Bars represent the best change from
baseline in the size of the target lesions using RESIST V 1.1
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