Post by Deleted on Jan 18, 2019 15:23:06 GMT
This sounds like good news, to me:
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Results: As of September 21, 2018, 8 Phase 1 subjects and 13 Phase 2 subjects were enrolled
and treated (9 males and 12 females, median age 67 years). The most common (≥15%) related
adverse events were nausea, diarrhea, fatigue, alopecia, decreased appetite, rash, vomiting, and
anemia. Fourteen subjects had at least one on-study scan (after 2 cycles). One subject
experienced a complete response (CR) after 6 cycles of therapy with normalization of CA19.9
(-76%) and confirmed after 8 cycles. Three subjects exhibited a partial response (PR): two after 2
cycles (39 and 47%) and one after 4 cycles of therapy (36%). Eight subjects had stable disease for
at least 2 months, and 4 subjects had PFS of at least 4 months. The disease control rate
(CR+PR+SD) was 86% in evaluable subjects while the overall response rate (CR+PR) was 29%.
(update in Results section)
Conclusions: RX-3117 in combination with nab-pac appears to be safe and well tolerated in
subjects with met-PC. Anti-tumor activity per RECIST was observed in 12 subjects. Phase 2 of the
clinical study is currently ongoing.
• The combination of RX-3117 and nab-pac appears safe and well-tolerated when
administered at the recommended Phase 2 dose
• Early responses were detected with an overall response rate of 38% in 24
subjects, and a disease control rate of 92% at 8 weeks.
• Pharmacokinetic results indicate that RX-3117 and nab-Pac do not appear to
interfere with the exposure or clearance of either drug.
• The study continues to enroll subjects with metastatic pancreatic cancer in
Stage 2.
The current National Comprehensive Cancer Network recommendations suggest
acceptable chemotherapy combinations for met-PC patients include FOLFIRINOX and
gemcitabine plus nab-paclitaxel (nab-pac). However, clinical trials are also recommended
due to the modest 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 for
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 (Chung VM, et al., J Clin Oncol 36, 2018
(suppl 4S; abstr 396)).
B
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 nab-pac 125 mg/m2
administered IV once weekly for 3 weeks with 1 week off per 4-week cycle.
• As of 09 January 2019, in the response evaluable population (24 subjects)
from the Phase 1 and Phase 2:
• Overall response rate was 38%
• 1 CR was observed after 6 cycles of therapy and confirmed after 8
cycles of therapy
• 8 PRs were observed: 4 after 2 cycles of therapy and 4 after 4 cycles
of therapy
• Disease control rate was 92% at 8 weeks (1 Complete Response/ 8 Partial
Responses/ 13 Stable Disease)
• Most subjects (69%) with CA 19-9 results exhibited reductions after 1 cycle
of therapy (-10% to -75%). One subject experienced a 46% increase but had
a partial response after 4 cycles.
• Most Treatment Emergent Adverse Events (TEAEs) considered related to RX-
3117, nab-Pac, or the combination were mild to moderate (83%).
• The most common related Grade 1-2 TEAEs were diarrhea (53%), nausea
(47%), fatigue (42%), rash (28%), alopecia (25%), anemia (19%), anorexia
(19%), peripheral sensory neuropathy (19%), abdominal discomfort (17%),
pyrexia (14%), constipation (11%), dehydration (11%), itching (11%), and
vomiting (11%).
• Grade 3-4 TEAEs related to RX-3117, nab-pac, or the combination were
neutropenia (29%), anemia (11%), diarrhea (8%), leucopenia (8%),
hypokalemia (5%), and acute kidney injury, dehydration, general weakness,
hypomagnesemia, mouth sores, nausea, neutropenic fever, peripheral sensory
neuropathy, platelet count decreased, protein-calorie malnutrition, vomiting
(1%).
• Some subjects received at least one dose reduction of nab-Pac (10/ 28%) or
RX-3117 (2/ 5.6%). Dose reductions occurred most frequently in Cycles 1-3
(40%, 30%, 20% respectively).
*Small non-target lesions present
**Subject discontinued at Cycle 13 with a complete response (withdrew consent)
Note: Six subjects discontinued prior to the first on-study scan, 5 subjects are currently on treatment but
have not completed the first on-study imaging assessment.
Abstract #420
Study Design
Baseline Characteristics (N=36)
==============================
C L
-------------------------------
Results: As of September 21, 2018, 8 Phase 1 subjects and 13 Phase 2 subjects were enrolled
and treated (9 males and 12 females, median age 67 years). The most common (≥15%) related
adverse events were nausea, diarrhea, fatigue, alopecia, decreased appetite, rash, vomiting, and
anemia. Fourteen subjects had at least one on-study scan (after 2 cycles). One subject
experienced a complete response (CR) after 6 cycles of therapy with normalization of CA19.9
(-76%) and confirmed after 8 cycles. Three subjects exhibited a partial response (PR): two after 2
cycles (39 and 47%) and one after 4 cycles of therapy (36%). Eight subjects had stable disease for
at least 2 months, and 4 subjects had PFS of at least 4 months. The disease control rate
(CR+PR+SD) was 86% in evaluable subjects while the overall response rate (CR+PR) was 29%.
(update in Results section)
Conclusions: RX-3117 in combination with nab-pac appears to be safe and well tolerated in
subjects with met-PC. Anti-tumor activity per RECIST was observed in 12 subjects. Phase 2 of the
clinical study is currently ongoing.
• The combination of RX-3117 and nab-pac appears safe and well-tolerated when
administered at the recommended Phase 2 dose
• Early responses were detected with an overall response rate of 38% in 24
subjects, and a disease control rate of 92% at 8 weeks.
• Pharmacokinetic results indicate that RX-3117 and nab-Pac do not appear to
interfere with the exposure or clearance of either drug.
• The study continues to enroll subjects with metastatic pancreatic cancer in
Stage 2.
The current National Comprehensive Cancer Network recommendations suggest
acceptable chemotherapy combinations for met-PC patients include FOLFIRINOX and
gemcitabine plus nab-paclitaxel (nab-pac). However, clinical trials are also recommended
due to the modest 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 for
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 (Chung VM, et al., J Clin Oncol 36, 2018
(suppl 4S; abstr 396)).
B
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 nab-pac 125 mg/m2
administered IV once weekly for 3 weeks with 1 week off per 4-week cycle.
• As of 09 January 2019, in the response evaluable population (24 subjects)
from the Phase 1 and Phase 2:
• Overall response rate was 38%
• 1 CR was observed after 6 cycles of therapy and confirmed after 8
cycles of therapy
• 8 PRs were observed: 4 after 2 cycles of therapy and 4 after 4 cycles
of therapy
• Disease control rate was 92% at 8 weeks (1 Complete Response/ 8 Partial
Responses/ 13 Stable Disease)
• Most subjects (69%) with CA 19-9 results exhibited reductions after 1 cycle
of therapy (-10% to -75%). One subject experienced a 46% increase but had
a partial response after 4 cycles.
• Most Treatment Emergent Adverse Events (TEAEs) considered related to RX-
3117, nab-Pac, or the combination were mild to moderate (83%).
• The most common related Grade 1-2 TEAEs were diarrhea (53%), nausea
(47%), fatigue (42%), rash (28%), alopecia (25%), anemia (19%), anorexia
(19%), peripheral sensory neuropathy (19%), abdominal discomfort (17%),
pyrexia (14%), constipation (11%), dehydration (11%), itching (11%), and
vomiting (11%).
• Grade 3-4 TEAEs related to RX-3117, nab-pac, or the combination were
neutropenia (29%), anemia (11%), diarrhea (8%), leucopenia (8%),
hypokalemia (5%), and acute kidney injury, dehydration, general weakness,
hypomagnesemia, mouth sores, nausea, neutropenic fever, peripheral sensory
neuropathy, platelet count decreased, protein-calorie malnutrition, vomiting
(1%).
• Some subjects received at least one dose reduction of nab-Pac (10/ 28%) or
RX-3117 (2/ 5.6%). Dose reductions occurred most frequently in Cycles 1-3
(40%, 30%, 20% respectively).
*Small non-target lesions present
**Subject discontinued at Cycle 13 with a complete response (withdrew consent)
Note: Six subjects discontinued prior to the first on-study scan, 5 subjects are currently on treatment but
have not completed the first on-study imaging assessment.
Abstract #420
Study Design
Baseline Characteristics (N=36)
==============================
C L