NCT03520075

Study of ASTX029 in Subjects With Advanced Solid Tumors

Completed Phase 1, PHASE2 Results posted Last updated 3 July 2025

What this trial tests

Phase 1, PHASE2 trial testing ASTX029 in Solid Tumor, Adult in 192 participants. Completed in 3 March 2025.

Timeline

7 May 2018

Primary endpoint
1 August 2024

3 March 2025

Quick facts

Lead sponsor	Taiho Oncology, Inc.
Phase	Phase 1, PHASE2
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	none
Primary purpose	treatment
Enrollment	192
Start date	7 May 2018
Primary completion	1 August 2024
Estimated completion	3 March 2025
Sites	31 locations across France, United Kingdom, United States, Spain

Drugs / interventions tested

• ASTX029 — full drug profile →
• ASTX029 — full drug profile →

Conditions studied

• Solid Tumor, Adult — all drugs for Solid Tumor, Adult →

Sponsor

Taiho Oncology, Inc. — full company profile →

Who can join

18 and older, any sex, with Solid Tumor, Adult. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Phase 1: Number of Participants With Dose Limiting Toxicities (DLTs) Primary · Cycle 1 (cycle length = 21 days)

DLTs were defined as adverse events (AEs) graded by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03 criteria that occurred during the first cycle of treatment and represented any 1 of the following: grade 4 thrombocytopenia of any duration; ≥grade 3 hematologic toxicity with complications (e.g., grade 3 thrombocytopenia with bleeding or transfusion requirement); febrile neutropenia of any duration or grade 4 neutropenia of 5 days or more duration; liver-associated abnormalities; ≥grade 2 eye disorders; symptomatic grade 2 cutaneous toxicities (inclu

Group	Value	95% CI
Phase 1A: Cohort 1 Dose Escalation	0
Phase 1A: Cohort 2 Dose Escalation	0
Phase 1A: Cohort 3 Dose Escalation	0
Phase 1A: Cohort 4 Dose Escalation	0
Phase 1A: Cohort 5 Dose Escalation	1
Phase 1A: Cohort 6 Dose Escalation	0
Phase 1A: Cohort 7 Dose Escalation	0
Phase 1A: Cohort 8 Dose Escalation	0
Phase 1A: Cohort 9 Dose Escalation	0
Phase 1A: Cohort 10 Dose Escalation	0
Phase 1A: Cohort 11 Dose Escalation	0
Phase 1A: Cohort 12 Dose Escalation	1

Phase 1: Number of Participants With Treatment Emergent Adverse Events (TEAEs) Primary · From first dose of study drug up to 30 days after last dose (Up to 74 months)

An AE is defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. TEAEs are defined as events that first occurred or worsened on or after the date of the first dose of study treatment until 30 days after the last dose of study treatment or until the start of a posttreatment alternative anti-cancer treatment, whichever occurs first, with the following exceptions: events that occurred after 30 days beyond the last dose of study treatment or the start of a posttreatment alternative anti-cancer treatment will also be considered

Group	Value	95% CI
Phase 1A: Cohort 1 Dose Escalation	3
Phase 1A: Cohort 2 Dose Escalation	3
Phase 1A: Cohort 3 Dose Escalation	3
Phase 1A: Cohort 4 Dose Escalation	5
Phase 1A: Cohort 5 Dose Escalation	10
Phase 1A: Cohort 6 Dose Escalation	6
Phase 1A: Cohort 7 Dose Escalation	3
Phase 1A: Cohort 8 Dose Escalation	3
Phase 1A: Cohort 9 Dose Escalation	3
Phase 1A: Cohort 10 Dose Escalation	3
Phase 1A: Cohort 11 Dose Escalation	7
Phase 1A: Cohort 12 Dose Escalation	7

Phase 2: Objective Response Rate (ORR) as Assessed by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 Primary · Every 2 cycles for the first 4 cycles and then every 4 cycles thereafter until disease progression (Up to 74 months)

The ORR was calculated as the number of evaluable participants whose best response was complete response (CR) or partial response (PR), divided by the total number of participants evaluable for ORR analysis. CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or nontarget) must have reduction in short axis to \<10 millimeters (mm). PR was defined as at least a 30 percent (%) decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Percentages were rounded off to the nearest single decimal place

Group	Value	95% CI
Phase 2: Cohort A	12.5	4.4 – 26.4
Phase 2: Cohort B	0	0 – 18.1
Phase 2: Cohort C	8.3	0.4 – 33.9
Phase 2: Cohort D	0	0 – 28.3
Phase 2: Cohort E	12.5	4.4 – 26.4
Phase 2: Cohort F	7.1	0.4 – 29.7

Phase 1: Area Under the Concentration-time Curve From Time Zero to 24 Hours (AUC0-24) of ASTX029 Secondary · Pre-dose on Day 1 of Cycles 1 and 2 and at 0.5, 1, 2, 3, 4, 6, and 8 hours post-dose on Day 1 of Cycles 1 and 2 (Cycle length = 21 days)

As per planned analysis, data for participants from Part A (Dose Escalation) and Part B (Expansion) were combined for Cohort 11 (200 mg). 2 participants who received 200 and 280 mg respectively, in Cycle 1 Day1 (C1D1), received 120 mg in Cycle 2 and Day 1 (C2D1) and hence counted in Cohort 10. 1 participant who received 280 mg in C1D1, received 200 mg in C2D1 and hence counted in Cohort 11.

Cycle 1 Day 1 (C1D1)

Group	Value	95% CI
Phase 1A: Cohort 1 Dose Escalation	277	± 20.1
Phase 1A: Cohort 2 Dose Escalation	361	± 222.0
Phase 1A: Cohort 3 Dose Escalation	1150	± 10.0
Phase 1A: Cohort 4 Dose Escalation	4020	± 83.0
Phase 1A: Cohort 5 Dose Escalation	7250	± 63.7
Phase 1A: Cohort 6 Dose Escalation	1810	± 126.9
Phase 1A: Cohort 7 Dose Escalation	3360	± 140.4
Phase 1A: Cohort 8 Dose Escalation	3080	± 128.2
Phase 1A: Cohort 9 Dose Escalation	6500	± 64.3
Phase 1A: Cohort 10 Dose Escalation	5710	± 27.1
Phase 1A Cohort 11 Dose Escalation and Phase 1B Dose Expansion	13400	± 46.4
Phase 1A: Cohort 12 Dose Escalation	17800	± 83.6

Cycle 2 Day 1 (C2D1)

Group	Value	95% CI
Phase 1A: Cohort 1 Dose Escalation	339	± 58.4
Phase 1A: Cohort 2 Dose Escalation	618	± 11.7
Phase 1A: Cohort 3 Dose Escalation	1410	± 61.4
Phase 1A: Cohort 4 Dose Escalation	3530	± 104.5
Phase 1A: Cohort 5 Dose Escalation	7550	± 76.9
Phase 1A: Cohort 6 Dose Escalation	2490	± 108.4
Phase 1A: Cohort 7 Dose Escalation	3710	± 106.0
Phase 1A: Cohort 8 Dose Escalation	3370	± 117.8
Phase 1A: Cohort 9 Dose Escalation	6430	± 71.6
Phase 1A: Cohort 10 Dose Escalation	7850	± 37.1
Phase 1A Cohort 11 Dose Escalation and Phase 1B Dose Expansion	15400	± 57.5
Phase 1A: Cohort 12 Dose Escalation	25600	± 91.9

Phase 1: Area Under the Concentration-time Curve From Time Zero to the Last Quantifiable Concentration (AUC0-last) of ASTX029 Secondary · Pre-dose on Day 1 of Cycles 1 and 2 and at 0.5, 1, 2, 3, 4, 6, and 8 hours post-dose on Day 1 of Cycles 1 and 2 (Cycle length = 21 days)

As per planned analysis, data for participants from Part A (Dose Escalation) and Part B (Expansion) were combined for Cohort 11 (200 mg). 2 participants who received 200 and 280 mg respectively, in C1D1 received 120 mg in C2D1 and hence counted in Cohort 10. 1 participant who received 280 mg in C1D1, received 200 mg in C2D1 and hence counted in Cohort 11.

C1D1

Group	Value	95% CI
Phase 1A: Cohort 1 Dose Escalation	262	± 18.5
Phase 1A: Cohort 2 Dose Escalation	347	± 215.6
Phase 1A: Cohort 3 Dose Escalation	1140	± 10.0
Phase 1A: Cohort 4 Dose Escalation	4020	± 82.9
Phase 1A: Cohort 5 Dose Escalation	7250	± 63.7
Phase 1A: Cohort 6 Dose Escalation	1740	± 137.5
Phase 1A: Cohort 7 Dose Escalation	3360	± 140.4
Phase 1A: Cohort 8 Dose Escalation	1620	± 215.6
Phase 1A: Cohort 9 Dose Escalation	6450	± 65.8
Phase 1A: Cohort 10 Dose Escalation	5710	± 26.9
Phase 1A Cohort 11 Dose Escalation and Phase 1B Dose Expansion	12800	± 51.2
Phase 1A: Cohort 12 Dose Escalation	17800	± 83.6

C2D1

Group	Value	95% CI
Phase 1A: Cohort 1 Dose Escalation	321	± 56.1
Phase 1A: Cohort 2 Dose Escalation	298	± 177.3
Phase 1A: Cohort 3 Dose Escalation	1410	± 61.5
Phase 1A: Cohort 4 Dose Escalation	3530	± 104.5
Phase 1A: Cohort 5 Dose Escalation	7530	± 77.2
Phase 1A: Cohort 6 Dose Escalation	2430	± 116.3
Phase 1A: Cohort 7 Dose Escalation	3660	± 104.2
Phase 1A: Cohort 8 Dose Escalation	3340	± 116.4
Phase 1A: Cohort 9 Dose Escalation	6450	± 72.0
Phase 1A: Cohort 10 Dose Escalation	7850	± 37.1
Phase 1A Cohort 11 Dose Escalation and Phase 1B Dose Expansion	13500	± 80.0
Phase 1A: Cohort 12 Dose Escalation	25300	± 93.7

Phase 1: Area Under the Concentration-time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of ASTX029 Secondary · Pre-dose on Day 1 of Cycles 1 and 2 and at 0.5, 1, 2, 3, 4, 6, and 8 hours post-dose on Day 1 of Cycles 1 and 2 (Cycle length = 21 days)

As per planned analysis, data for participants from Part A (Dose Escalation) and Part B (Expansion) were combined for Cohort 11 (200 mg). 2 participants who received 200 and 280 mg respectively, in C1D1, received 120 mg in C2D1 and hence counted in Cohort 10. 1 participant who received 280 mg in C1D1, received 200 mg in C2D1 and hence counted in Cohort 11.

C1D1

Group	Value	95% CI
Phase 1A: Cohort 1 Dose Escalation	327	± 3.6
Phase 1A: Cohort 2 Dose Escalation	358	± 209.2
Phase 1A: Cohort 3 Dose Escalation	1150	± 14.1
Phase 1A: Cohort 4 Dose Escalation	4050	± 82.5
Phase 1A: Cohort 5 Dose Escalation	8170	± 53.5
Phase 1A: Cohort 6 Dose Escalation	1180	± 112.9
Phase 1A: Cohort 7 Dose Escalation	3390	± 139.3
Phase 1A: Cohort 8 Dose Escalation	3120	± 126.3
Phase 1A: Cohort 9 Dose Escalation	6520	± 66.6
Phase 1A: Cohort 10 Dose Escalation	5770	± 26.7
Phase 1A Cohort 11 Dose Escalation and Phase 1B Dose Expansion	13500	± 47.1
Phase 1A: Cohort 12 Dose Escalation	17900	± 83.1

C2D1

Group	Value	95% CI
Phase 1A: Cohort 1 Dose Escalation	346	± 52.9
Phase 1A: Cohort 2 Dose Escalation	243	± 228.9
Phase 1A: Cohort 3 Dose Escalation	1430	± 60.9
Phase 1A: Cohort 4 Dose Escalation	5160	± 55.0
Phase 1A: Cohort 5 Dose Escalation	7670	± 75.3
Phase 1A: Cohort 6 Dose Escalation	2470	± 116.1
Phase 1A: Cohort 7 Dose Escalation	3190	± 169.8
Phase 1A: Cohort 8 Dose Escalation	3420	± 113.6
Phase 1A: Cohort 9 Dose Escalation	5590	± 101.3
Phase 1A: Cohort 10 Dose Escalation	7930	± 37.2
Phase 1A Cohort 11 Dose Escalation and Phase 1B Dose Expansion	15700	± 59.0
Phase 1A: Cohort 12 Dose Escalation	25600	± 92.2

Phase 1: Maximum Observed Plasma Concentration (Cmax) of ASTX029 Secondary · Pre-dose on Day 1 of Cycles 1 and 2 and at 0.5, 1, 2, 3, 4, 6, and 8 hours post-dose on Day 1 of Cycles 1 and 2 (Cycle length = 21 days)

As per planned analysis, data for participants from Part A (Dose Escalation) and Part B (Expansion) were combined for Cohort 11 (200 mg). 2 participants who received 200 and 280 mg respectively, in C1D1, received 120 mg in C2D1 and hence counted in Cohort 10. 1 participant who received 280 mg in C1D1, received 200 mg in C2D1 and hence counted in Cohort 11.

C1D1

Group	Value	95% CI
Phase 1A: Cohort 1 Dose Escalation	109	± 48.5
Phase 1A: Cohort 2 Dose Escalation	217	± 165.4
Phase 1A: Cohort 3 Dose Escalation	469	± 9.5
Phase 1A: Cohort 4 Dose Escalation	1650	± 56.8
Phase 1A: Cohort 5 Dose Escalation	1850	± 66.7
Phase 1A: Cohort 6 Dose Escalation	496	± 127.7
Phase 1A: Cohort 7 Dose Escalation	1490	± 141.7
Phase 1A: Cohort 8 Dose Escalation	742	± 301.5
Phase 1A: Cohort 9 Dose Escalation	2840	± 30.8
Phase 1A: Cohort 10 Dose Escalation	2060	± 49.5
Phase 1A Cohort 11 Dose Escalation and Phase 1B Dose Expansion	5240	± 61.0
Phase 1A: Cohort 12 Dose Escalation	6040	± 58.4

C2D1

Group	Value	95% CI
Phase 1A: Cohort 1 Dose Escalation	143	± 177.8
Phase 1A: Cohort 2 Dose Escalation	107	± 119.2
Phase 1A: Cohort 3 Dose Escalation	598	± 111.0
Phase 1A: Cohort 4 Dose Escalation	903	± 228.8
Phase 1A: Cohort 5 Dose Escalation	1830	± 177.6
Phase 1A: Cohort 6 Dose Escalation	641	± 91.4
Phase 1A: Cohort 7 Dose Escalation	1710	± 124.4
Phase 1A: Cohort 8 Dose Escalation	2330	± 130.8
Phase 1A: Cohort 9 Dose Escalation	1860	± 55.8
Phase 1A: Cohort 10 Dose Escalation	2360	± 40.9
Phase 1A Cohort 11 Dose Escalation and Phase 1B Dose Expansion	5350	± 78.7
Phase 1A: Cohort 12 Dose Escalation	8070	± 50.7

Phase 1: Minimum Plasma Concentration (Cmin) of ASTX029 Secondary · Pre-dose and at 0.5, 1, 2, 3, 4, 6, and 8 hours post-dose on Day 1 of Cycle 2 (Cycle length = 21 days)

As per planned analysis, data for participants from Part A (Dose Escalation) and Part B (Expansion) were combined for Cohort 11 (200 mg). 2 participants who received 200 and 280 mg respectively, in C1D1, received 120 mg in C2D1 and hence counted in Cohort 10. 1 participant who received 280 mg in C1D1, received 200 mg in C2D1 and hence counted in Cohort 11. Data for Cmin was calculated and analyzed for C2D1 only.

Group	Value	95% CI
Phase 1A: Cohort 1 Dose Escalation	4.38	± 86.7
Phase 1A: Cohort 2 Dose Escalation	1.45	± 173.2
Phase 1A: Cohort 3 Dose Escalation	23.4	± 127.8
Phase 1A: Cohort 4 Dose Escalation	19.3	± 149.7
Phase 1A: Cohort 5 Dose Escalation	18.1	± 39.7
Phase 1A: Cohort 6 Dose Escalation	7.88	± 79.3
Phase 1A: Cohort 7 Dose Escalation	68.1	± 128.8
Phase 1A: Cohort 8 Dose Escalation	8.68	± 64.0
Phase 1A: Cohort 9 Dose Escalation	20.1	± 114.7
Phase 1A: Cohort 10 Dose Escalation	85.3	± 206.9
Phase 1A Cohort 11 Dose Escalation and Phase 1B Dose Expansion	188	± 194.3
Phase 1A: Cohort 12 Dose Escalation	168	± 85.6

Phase 1: Time to Reach Maximum Concentration (Tmax) of ASTX029 Secondary · Pre-dose on Day 1 of Cycles 1 and 2 and at 0.5, 1, 2, 3, 4, 6, and 8 hours post-dose on Day 1 of Cycles 1 and 2 (Cycle length = 21 days)

As per planned analysis, data for participants from Part A (Dose Escalation) and Part B (Expansion) were combined for Cohort 11 (200 mg). 2 participants who received 200 and 280 mg respectively, in C1D1, received 120 mg in C2D1 and hence counted in Cohort 10. 1 participant who received 280 mg in C1D1, received 200 mg in C2D1 and hence counted in Cohort 11.

C1D1

Group	Value	95% CI
Phase 1A: Cohort 1 Dose Escalation	1.08	0.57 – 3.05
Phase 1A: Cohort 2 Dose Escalation	0.50	0.50 – 0.58
Phase 1A: Cohort 3 Dose Escalation	0.55	0.47 – 0.97
Phase 1A: Cohort 4 Dose Escalation	0.50	0.50 – 1.00
Phase 1A: Cohort 5 Dose Escalation	0.71	0.43 – 4.08
Phase 1A: Cohort 6 Dose Escalation	3.03	1.08 – 5.73
Phase 1A: Cohort 7 Dose Escalation	1.00	0.98 – 3.00
Phase 1A: Cohort 8 Dose Escalation	1.07	1.00 – 4.02
Phase 1A: Cohort 9 Dose Escalation	1.00	0.47 – 1.88
Phase 1A: Cohort 10 Dose Escalation	1.88	0.53 – 1.93
Phase 1A Cohort 11 Dose Escalation and Phase 1B Dose Expansion	1.97	0.50 – 6.00
Phase 1a: Cohort 12	2.03	1.00 – 4.00

C2D1

Group	Value	95% CI
Phase 1A: Cohort 1 Dose Escalation	0.53	0.50 – 2.20
Phase 1A: Cohort 2 Dose Escalation	1.00	0.55 – 1.05
Phase 1A: Cohort 3 Dose Escalation	0.50	0.47 – 0.92
Phase 1A: Cohort 4 Dose Escalation	2.52	0.92 – 5.7
Phase 1A: Cohort 5 Dose Escalation	0.55	0.50 – 1.00
Phase 1A: Cohort 6 Dose Escalation	2.48	0.52 – 3.85
Phase 1A: Cohort 7 Dose Escalation	1.02	0.50 – 7.53
Phase 1A: Cohort 8 Dose Escalation	1.52	1.00 – 2.03
Phase 1A: Cohort 9 Dose Escalation	3.00	2.93 – 5.67
Phase 1A: Cohort 10 Dose Escalation	2.1	1.08 – 4
Phase 1A Cohort 11 Dose Escalation and Phase 1B Dose Expansion	2.02	0.92 – 7.52
Phase 1a: Cohort 12	1.90	0.55 – 3.85

Phase 1: Elimination Half-Life (T1/2) of ASTX029 Secondary · Pre-dose on Day 1 of Cycles 1 and 2 and at 0.5, 1, 2, 3, 4, 6, and 8 hours post-dose on Day 1 of Cycles 1 and 2 (Cycle length = 21 days)

As per planned analysis, data for participants from Part A (Dose Escalation) and Part B (Expansion) were combined for Cohort 11 (200 mg). 2 participants who received 200 and 280 mg respectively, in C1D1, received 120 mg in C2D1 and hence counted in Cohort 10. 1 participant who received 280 mg in C1D1, received 200 mg in C2D1 and hence counted in Cohort 11.

C1D1

Group	Value	95% CI
Phase 1A: Cohort 1 Dose Escalation	2.42	± 42.1
Phase 1A: Cohort 2 Dose Escalation	1.63	± 18.7
Phase 1A: Cohort 3 Dose Escalation	4.42	± 1.8
Phase 1A: Cohort 4 Dose Escalation	3.75	± 26.9
Phase 1A: Cohort 5 Dose Escalation	3.84	± 21.8
Phase 1A: Cohort 6 Dose Escalation	2.08	± 102.4
Phase 1A: Cohort 7 Dose Escalation	4.28	± 11.6
Phase 1A: Cohort 8 Dose Escalation	5.68	± 31.7
Phase 1A: Cohort 9 Dose Escalation	3.30	± 74.7
Phase 1A: Cohort 10 Dose Escalation	4.00	± 13.6
Phase 1A Cohort 11 Dose Escalation and Phase 1B Dose Expansion	3.92	± 40.9
Phase 1A: Cohort 12 Dose Escalation	3.71	± 32.9

C2D1

Group	Value	95% CI
Phase 1A: Cohort 1 Dose Escalation	3.37	± 119.7
Phase 1A: Cohort 2 Dose Escalation	1.85	± 64.8
Phase 1A: Cohort 3 Dose Escalation	4.98	± 31.5
Phase 1A: Cohort 4 Dose Escalation	3.61	± 13.5
Phase 1A: Cohort 5 Dose Escalation	4.11	± 15.9
Phase 1A: Cohort 6 Dose Escalation	2.58	± 95.1
Phase 1A: Cohort 7 Dose Escalation	1.01	± 11.6
Phase 1A: Cohort 8 Dose Escalation	3.13	± 276.4
Phase 1A: Cohort 9 Dose Escalation	4.67	± 24.1
Phase 1A: Cohort 10 Dose Escalation	3.88	± 25.6
Phase 1A Cohort 11 Dose Escalation and Phase 1B Dose Expansion	3.80	± 47.2
Phase 1A: Cohort 12 Dose Escalation	1.28	± 72.1

Phase 1: Effect of Food on AUC0-24 of ASTX029 Secondary · Pre-dose on Day 1 of Cycles 1 and 2 and at 0.5, 1, 2, 3, 4, 6, and 8 hours post-dose on Day 1 of Cycles 1 and 2 (Cycle length = 21 days)

The food effect was to be analyzed only for tablet dosage forms. The participants who were administered 80 mg and 120 mg tablets, under both fed and fasted conditions were reported. As 200 mg dose was administered, as tablets, only under fasted conditions, hence food effect was not assessed for 200 mg dose. The statistical comparison between fed and fasted state treatment arm groups of 80 mg and 120 mg doses is reported in this outcome measure for food effect. The 2 participants who received 200 and 280 mg respectively, in C1D1, received 120 mg in C2D1 and hence counted in Cohort 10.

C1D1

Group	Value	95% CI
Phase 1A: Cohort 6 Dose Escalation	1810	± 126.9
Phase 1A: Cohort 7 Dose Escalation	3360	± 140.4
Phase 1A: Cohort 9 Dose Escalation	6500	± 64.3
Phase 1A: Cohort 10 Dose Escalation	5710	± 27.1

C2D1

Group	Value	95% CI
Phase 1A: Cohort 6 Dose Escalation	2490	± 108.4
Phase 1A: Cohort 7 Dose Escalation	3710	± 106.0
Phase 1A: Cohort 9 Dose Escalation	6430	± 71.6
Phase 1A: Cohort 10 Dose Escalation	7850	± 37.1

Phase 1: Effect of Food on AUC0-inf of ASTX029 Secondary · Pre-dose on Day 1 of Cycles 1 and 2 and at 0.5, 1, 2, 3, 4, 6, and 8 hours post-dose on Day 1 of Cycles 1 and 2 (Cycle length = 21 days)

The food effect was to be analyzed only for tablet dosage forms. The participants who were administered 80 mg and 120 mg tablets, under both fed and fasted conditions were reported. As 200 mg dose was administered, as tablets, only under fasted conditions, hence food effect was not assessed for 200 mg dose. The statistical comparison between fed and fasted state treatment arm groups of 80 mg and 120 mg doses is reported in this outcome measure for food effect. The 2 participants who received 200 and 280 mg respectively, in C1D1, received 120 mg in C2D1 and hence counted in Cohort 10.

C1D1

Group	Value	95% CI
Phase 1A: Cohort 6 Dose Escalation	1180	± 112.9
Phase 1A: Cohort 7 Dose Escalation	3390	± 139.3
Phase 1A: Cohort 9 Dose Escalation	6520	± 66.6
Phase 1A: Cohort 10 Dose Escalation	5770	± 26.7

C2D1

Group	Value	95% CI
Phase 1A: Cohort 6 Dose Escalation	2470	± 116.1
Phase 1A: Cohort 7 Dose Escalation	3190	± 169.8
Phase 1A: Cohort 9 Dose Escalation	5590	± 101.3
Phase 1A: Cohort 10 Dose Escalation	7930	± 37.2

Adverse events — posted to ClinicalTrials.gov

Time frame: From first dose of study drug up to end of the study (Up to 82 months). Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Phase 1A: Cohort 1 Dose Escalation

Serious: 0/3 (0%)

Deaths: 3/3

Phase 1A: Cohort 2 Dose Escalation

Serious: 1/3 (33%)

Deaths: 2/3

Phase 1A: Cohort 3 Dose Escalation

Serious: 2/3 (67%)

Deaths: 3/3

Phase 1A: Cohort 4 Dose Escalation

Serious: 2/5 (40%)

Deaths: 3/5

Phase 1A: Cohort 5 Dose Escalation

Serious: 7/10 (70%)

Deaths: 9/10

Phase 1A: Cohort 6 Dose Escalation

Serious: 1/6 (17%)

Deaths: 4/6

Phase 1A: Cohort 7 Dose Escalation

Serious: 2/3 (67%)

Deaths: 3/3

Phase 1A: Cohort 8 Dose Escalation

Serious: 0/3 (0%)

Deaths: 3/3

Phase 1A: Cohort 9 Dose Escalation

Serious: 1/3 (33%)

Deaths: 3/3

Phase 1A: Cohort 10 Dose Escalation

Serious: 1/3 (33%)

Deaths: 1/3

Phase 1A: Cohort 11 Dose Escalation

Serious: 3/7 (43%)

Deaths: 5/7

Phase 1A: Cohort 12 Dose Escalation

Serious: 1/7 (14%)

Deaths: 7/7

Phase 1B Dose Expansion

Serious: 9/20 (45%)

Deaths: 13/20

Phase 2: Cohort A

Serious: 11/32 (34%)

Deaths: 23/32

Phase 2: Cohort B

Serious: 5/15 (33%)

Deaths: 13/15

Phase 2: Cohort C

Serious: 4/12 (33%)

Deaths: 10/12

Phase 2: Cohort D

Serious: 3/9 (33%)

Deaths: 5/9

Phase 2: Cohort E

Serious: 12/32 (38%)

Deaths: 14/32

Phase 2: Cohort F

Serious: 4/14 (29%)

Deaths: 11/14

Serious adverse events (76 terms)

Reaction	System	Phase 1A: Cohort 1 Dose Es…	Phase 1A: Cohort 2 Dose Es…	Phase 1A: Cohort 3 Dose Es…	Phase 1A: Cohort 4 Dose Es…	Phase 1A: Cohort 5 Dose Es…	Phase 1A: Cohort 6 Dose Es…	Phase 1A: Cohort 7 Dose Es…	Phase 1A: Cohort 8 Dose Es…	Phase 1A: Cohort 9 Dose Es…	Phase 1A: Cohort 10 Dose E…	Phase 1A: Cohort 11 Dose E…	Phase 1A: Cohort 12 Dose E…	Phase 1B Dose Expansion	Phase 2: Cohort A	Phase 2: Cohort B	Phase 2: Cohort C	Phase 2: Cohort D	Phase 2: Cohort E	Phase 2: Cohort F
Pneumonia	Infections and infestations	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Diarrhoea	Gastrointestinal disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Sepsis	Infections and infestations	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Acute kidney injury	Renal and urinary disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Anaemia	Blood and lymphatic system disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Leukocytosis	Blood and lymphatic system disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Atrial fibrillation	Cardiac disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Atrial flutter	Cardiac disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Abdominal pain	Gastrointestinal disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Intestinal obstruction	Gastrointestinal disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Large intestinal obstruction	Gastrointestinal disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Erosive duodenitis	Gastrointestinal disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Upper gastrointestinal haemorrhage	Gastrointestinal disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Ascites	Gastrointestinal disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Nausea	Gastrointestinal disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Colitis	Gastrointestinal disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Constipation	Gastrointestinal disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Gastrointestinal haemorrhage	Gastrointestinal disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Vomiting	Gastrointestinal disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Abdominal pain upper	Gastrointestinal disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Abdominal strangulated hernia	Gastrointestinal disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Gastritis	Gastrointestinal disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Inguinal hernia	Gastrointestinal disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Intestinal perforation	Gastrointestinal disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Pancreatitis	Gastrointestinal disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—

Other adverse events (306 terms — click to expand)

Reaction	System	Phase 1A: Cohort 1 Dose Es…	Phase 1A: Cohort 2 Dose Es…	Phase 1A: Cohort 3 Dose Es…	Phase 1A: Cohort 4 Dose Es…	Phase 1A: Cohort 5 Dose Es…	Phase 1A: Cohort 6 Dose Es…	Phase 1A: Cohort 7 Dose Es…	Phase 1A: Cohort 8 Dose Es…	Phase 1A: Cohort 9 Dose Es…	Phase 1A: Cohort 10 Dose E…	Phase 1A: Cohort 11 Dose E…	Phase 1A: Cohort 12 Dose E…	Phase 1B Dose Expansion	Phase 2: Cohort A	Phase 2: Cohort B	Phase 2: Cohort C	Phase 2: Cohort D	Phase 2: Cohort E	Phase 2: Cohort F
Diarrhoea	Gastrointestinal disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Nausea	Gastrointestinal disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Fatigue	General disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Anaemia	Blood and lymphatic system disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Vomiting	Gastrointestinal disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Abdominal pain	Gastrointestinal disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Decreased appetite	Metabolism and nutrition disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Dermatitis acneiform	Skin and subcutaneous tissue disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Urinary tract infection	Infections and infestations	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Hypomagnesaemia	Metabolism and nutrition disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Dry skin	Skin and subcutaneous tissue disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Asthenia	General disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Oedema peripheral	General disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Aspartate aminotransferase increased	Investigations	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Alanine aminotransferase increased	Investigations	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Hyperglycaemia	Metabolism and nutrition disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Pruritus	Skin and subcutaneous tissue disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Rash	Skin and subcutaneous tissue disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Vision blurred	Eye disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Constipation	Gastrointestinal disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Dry mouth	Gastrointestinal disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Dyspepsia	Gastrointestinal disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Pyrexia	General disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
COVID-19	Infections and infestations	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Hypoalbuminaemia	Metabolism and nutrition disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Hyponatraemia	Metabolism and nutrition disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Dehydration	Metabolism and nutrition disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Back pain	Musculoskeletal and connective tissue disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Sinus tachycardia	Cardiac disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Arthralgia	Musculoskeletal and connective tissue disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Headache	Nervous system disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Dizziness	Nervous system disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Dyspnoea	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Rash maculo-papular	Skin and subcutaneous tissue disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Alopecia	Skin and subcutaneous tissue disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Visual impairment	Eye disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Abdominal pain upper	Gastrointestinal disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Stomatitis	Gastrointestinal disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Chills	General disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Blood alkaline phosphatase increased	Investigations	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—

Most-reported serious reactions: Pneumonia, Diarrhoea, Sepsis, Acute kidney injury, Anaemia, Leukocytosis, Atrial fibrillation, Atrial flutter.

Data from ClinicalTrials.gov NCT03520075 adverse events section.

Sponsor's own description

This study is a first-in-human, open-label, multicenter, Phase 1-2 study to assess the safety, pharmacokinetics, pharmacodynamics, and preliminary clinical activity of ASTX029 administered orally to participants with advanced solid malignancies who are not candidates for approved or available therapies.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. The MAPK and AMPK signalings: interplay and implication in targeted cancer therapy.
   Yuan J, Dong X, Yap J, Hu J. · · 2020 · cited 388× · PMID 32807225 · DOI 10.1186/s13045-020-00949-4
2. RAS, wanted dead or alive: Advances in targeting RAS mutant cancers.
   Stalnecker CA, Der CJ. · · 2020 · cited 76× · PMID 32209699 · DOI 10.1126/scisignal.aay6013
3. Emerging Targeted Therapies in Advanced Non-Small-Cell Lung Cancer.
   Li S, de Camargo Correia GS, Wang J, Manochakian R, et al · · 2023 · cited 47× · PMID 37296863 · DOI 10.3390/cancers15112899
4. Genomic landscape of clinically acquired resistance alterations in patients treated with KRAS&lt;sup&gt;G12C&lt;/sup&gt; inhibitors.
   Riedl JM, Fece de la Cruz F, Lin JJ, Parseghian C, et al · · 2025 · cited 30× · PMID 39914665 · DOI 10.1016/j.annonc.2025.01.020
5. Metabolic landscapes in sarcomas.
   Miallot R, Galland F, Millet V, Blay JY, et al · · 2021 · cited 20× · PMID 34294128 · DOI 10.1186/s13045-021-01125-y
6. ASTX029, a Novel Dual-mechanism ERK Inhibitor, Modulates Both the Phosphorylation and Catalytic Activity of ERK.
   Munck JM, Berdini V, Bevan L, Brothwood JL, et al · · 2021 · cited 18× · PMID 34330842 · DOI 10.1158/1535-7163.mct-20-0909
7. TMEM176B Promotes EMT via FGFR/JNK Signalling in Development and Tumourigenesis of Lung Adenocarcinoma.
   Sun PH, Xia S, Yuan R, Zhang B, et al · · 2024 · cited 6× · PMID 39001509 · DOI 10.3390/cancers16132447
8. Lung cancer organoid-based drug evaluation models and new drug development application trends.
   Lee E, Lee SY, Seong YJ, Ku B, et al · · 2024 · cited 4× · PMID 39830742 · DOI 10.21037/tlcr-24-603