Trial Outcomes & Findings for Phase II Study of Ilorasertib (ABT348) in Patients With CDKN2A Deficient Solid Tumors (NCT NCT02478320)

NCT ID: NCT02478320

Last Updated: 2023-07-17

Results Overview

Partial or complete response to ilorasertib

• Recruitment status: TERMINATED
• Study phase: PHASE2
• Target enrollment: 12 participants
• Primary outcome timeframe: through study completion, maximum 18 months
• Results posted on: 2023-07-17

Participant Flow

Patients were recruited at the Phase I unit at MD Anderson Cancer Center beginning 08/05/16. Enrollment was closed to new patients on 06/09/21 because of sponsor's decision to stop manufacturing the drug. The trial was terminated on 05/12/22.

Some patients who consented to join the study were ultimately not treated either because of screen failure or imminent loss of drug supply

Participant milestones

Measure	Part 1 For evaluation of response rate in patients with cancers harboring CDKN2A deletion or mutation	Part 2 Tumor-specific Expansion For evaluation of response rate in a specific tumor type harboring CDKN2A deletion or mutation
Overall Study STARTED	12	0
Overall Study COMPLETED	0	0
Overall Study NOT COMPLETED	12	0

Reasons for withdrawal

Measure	Part 1 For evaluation of response rate in patients with cancers harboring CDKN2A deletion or mutation	Part 2 Tumor-specific Expansion For evaluation of response rate in a specific tumor type harboring CDKN2A deletion or mutation
Overall Study Adverse Event	2	0
Overall Study Death	1	0
Overall Study Lack of Efficacy	4	0
Overall Study Withdrawal by Subject	2	0
Overall Study Screen Failure	3	0

Baseline Characteristics

Phase II Study of Ilorasertib (ABT348) in Patients With CDKN2A Deficient Solid Tumors

Baseline characteristics by cohort

Measure	Part 1 n=12 Participants For evaluation of response rate in patients with cancers harboring CDKN2A deletion or mutation	Part 2 Tumor-specific Expansion For evaluation of response rate in a specific tumor type harboring CDKN2A deletion or mutation	Total n=12 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	7 Participants n=5 Participants	0 Participants n=7 Participants	7 Participants n=5 Participants
Age, Categorical >=65 years	5 Participants n=5 Participants	0 Participants n=7 Participants	5 Participants n=5 Participants
Sex: Female, Male Female	5 Participants n=5 Participants	0 Participants n=7 Participants	5 Participants n=5 Participants
Sex: Female, Male Male	7 Participants n=5 Participants	0 Participants n=7 Participants	7 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	11 Participants n=5 Participants	0 Participants n=7 Participants	11 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) White	11 Participants n=5 Participants	0 Participants n=7 Participants	11 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Region of Enrollment United States	12 Participants n=5 Participants	0 Participants n=7 Participants	12 Participants n=5 Participants

PRIMARY outcome

Timeframe: through study completion, maximum 18 months

Population: Patients with tumors harboring CDKN2A deletion or mutation

Partial or complete response to ilorasertib

Outcome measures

Measure	Part 1 n=9 Participants For evaluation of response rate in patients with cancers harboring CDKN2A deletion or mutation	Part 2 Tumor-specific Expansion For evaluation of response rate in a specific tumor type harboring CDKN2A deletion or mutation
Response Rate Partial Response	1 Participants	0 Participants
Response Rate Complete Response	0 Participants	0 Participants

PRIMARY outcome

Timeframe: through study completion, maximum 18 months

Population: Patients with tumors harboring CDKN2A deletion or mutation

Selection of specific tumor type where the drug is potentially active for recruitment of additional patients (expansion)

Outcome measures

Measure	Part 1 n=9 Participants For evaluation of response rate in patients with cancers harboring CDKN2A deletion or mutation	Part 2 Tumor-specific Expansion For evaluation of response rate in a specific tumor type harboring CDKN2A deletion or mutation
Efficacy Signal Pancreatic cancer	1 Participants	0 Participants
Efficacy Signal Sarcoma	3 Participants	0 Participants
Efficacy Signal Esophageal	1 Participants	0 Participants
Efficacy Signal GIST	1 Participants	0 Participants
Efficacy Signal Cholangiocarcinoma	2 Participants	0 Participants
Efficacy Signal Oral cancer	1 Participants	0 Participants

SECONDARY outcome

Timeframe: through study completion, maximum 18 months'

Population: Patients with tumors harboring CDKN2A deletion or mutation

Safety and tolerability of ilorasertib.

Outcome measures

Measure	Part 1 n=9 Participants For evaluation of response rate in patients with cancers harboring CDKN2A deletion or mutation	Part 2 Tumor-specific Expansion For evaluation of response rate in a specific tumor type harboring CDKN2A deletion or mutation
Safety and Tolerability Serious adverse events	5 events	—
Safety and Tolerability Other adverse events	20 events	—

SECONDARY outcome

Timeframe: Cycle 1 Day 1 at up to 72 hours prior to the first dose and 2-4 hours after the second dose

Population: No data was collected

Assessment of the pharmacodynamic effects of ilorasertib by immunohistochemistry for phospho-histone H3

Outcome measures

Outcome data not reported

Adverse Events

Part 1

Serious events: 5 serious events

Other events: 7 other events

Deaths: 1 deaths

Part 2 Tumor-specific Expansion

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Measure	Part 1 n=9 participants at risk For evaluation of response rate in patients with cancers harboring CDKN2A deletion or mutation	Part 2 Tumor-specific Expansion For evaluation of response rate in a specific tumor type harboring CDKN2A deletion or mutation
Infections and infestations Sepsis	11.1% 1/9 • Adverse events were collected after the first dose until end of treatment, death, or loss to follow up, maximum 18 months Part 2 Tumor-specific expansion (trial was terminated before this part was reached)	— 0/0 • Adverse events were collected after the first dose until end of treatment, death, or loss to follow up, maximum 18 months Part 2 Tumor-specific expansion (trial was terminated before this part was reached)
Gastrointestinal disorders Vomiting	11.1% 1/9 • Adverse events were collected after the first dose until end of treatment, death, or loss to follow up, maximum 18 months Part 2 Tumor-specific expansion (trial was terminated before this part was reached)	— 0/0 • Adverse events were collected after the first dose until end of treatment, death, or loss to follow up, maximum 18 months Part 2 Tumor-specific expansion (trial was terminated before this part was reached)
General disorders Uncontrolled pain	11.1% 1/9 • Adverse events were collected after the first dose until end of treatment, death, or loss to follow up, maximum 18 months Part 2 Tumor-specific expansion (trial was terminated before this part was reached)	— 0/0 • Adverse events were collected after the first dose until end of treatment, death, or loss to follow up, maximum 18 months Part 2 Tumor-specific expansion (trial was terminated before this part was reached)
Vascular disorders Hypertension	11.1% 1/9 • Adverse events were collected after the first dose until end of treatment, death, or loss to follow up, maximum 18 months Part 2 Tumor-specific expansion (trial was terminated before this part was reached)	— 0/0 • Adverse events were collected after the first dose until end of treatment, death, or loss to follow up, maximum 18 months Part 2 Tumor-specific expansion (trial was terminated before this part was reached)
Musculoskeletal and connective tissue disorders Cervical stenosis	11.1% 1/9 • Adverse events were collected after the first dose until end of treatment, death, or loss to follow up, maximum 18 months Part 2 Tumor-specific expansion (trial was terminated before this part was reached)	— 0/0 • Adverse events were collected after the first dose until end of treatment, death, or loss to follow up, maximum 18 months Part 2 Tumor-specific expansion (trial was terminated before this part was reached)

Other adverse events

Measure	Part 1 n=9 participants at risk For evaluation of response rate in patients with cancers harboring CDKN2A deletion or mutation	Part 2 Tumor-specific Expansion For evaluation of response rate in a specific tumor type harboring CDKN2A deletion or mutation
Blood and lymphatic system disorders Thrombocytopenia	22.2% 2/9 • Adverse events were collected after the first dose until end of treatment, death, or loss to follow up, maximum 18 months Part 2 Tumor-specific expansion (trial was terminated before this part was reached)	— 0/0 • Adverse events were collected after the first dose until end of treatment, death, or loss to follow up, maximum 18 months Part 2 Tumor-specific expansion (trial was terminated before this part was reached)
Gastrointestinal disorders Oral mucositis	11.1% 1/9 • Adverse events were collected after the first dose until end of treatment, death, or loss to follow up, maximum 18 months Part 2 Tumor-specific expansion (trial was terminated before this part was reached)	— 0/0 • Adverse events were collected after the first dose until end of treatment, death, or loss to follow up, maximum 18 months Part 2 Tumor-specific expansion (trial was terminated before this part was reached)
Gastrointestinal disorders Dysphagia	11.1% 1/9 • Adverse events were collected after the first dose until end of treatment, death, or loss to follow up, maximum 18 months Part 2 Tumor-specific expansion (trial was terminated before this part was reached)	— 0/0 • Adverse events were collected after the first dose until end of treatment, death, or loss to follow up, maximum 18 months Part 2 Tumor-specific expansion (trial was terminated before this part was reached)
General disorders Dehydration	33.3% 3/9 • Adverse events were collected after the first dose until end of treatment, death, or loss to follow up, maximum 18 months Part 2 Tumor-specific expansion (trial was terminated before this part was reached)	— 0/0 • Adverse events were collected after the first dose until end of treatment, death, or loss to follow up, maximum 18 months Part 2 Tumor-specific expansion (trial was terminated before this part was reached)
Nervous system disorders Confusion	11.1% 1/9 • Adverse events were collected after the first dose until end of treatment, death, or loss to follow up, maximum 18 months Part 2 Tumor-specific expansion (trial was terminated before this part was reached)	— 0/0 • Adverse events were collected after the first dose until end of treatment, death, or loss to follow up, maximum 18 months Part 2 Tumor-specific expansion (trial was terminated before this part was reached)
General disorders Fever	11.1% 1/9 • Adverse events were collected after the first dose until end of treatment, death, or loss to follow up, maximum 18 months Part 2 Tumor-specific expansion (trial was terminated before this part was reached)	— 0/0 • Adverse events were collected after the first dose until end of treatment, death, or loss to follow up, maximum 18 months Part 2 Tumor-specific expansion (trial was terminated before this part was reached)
Blood and lymphatic system disorders Neutropenia	11.1% 1/9 • Adverse events were collected after the first dose until end of treatment, death, or loss to follow up, maximum 18 months Part 2 Tumor-specific expansion (trial was terminated before this part was reached)	— 0/0 • Adverse events were collected after the first dose until end of treatment, death, or loss to follow up, maximum 18 months Part 2 Tumor-specific expansion (trial was terminated before this part was reached)
Renal and urinary disorders Proteinuria	11.1% 1/9 • Adverse events were collected after the first dose until end of treatment, death, or loss to follow up, maximum 18 months Part 2 Tumor-specific expansion (trial was terminated before this part was reached)	— 0/0 • Adverse events were collected after the first dose until end of treatment, death, or loss to follow up, maximum 18 months Part 2 Tumor-specific expansion (trial was terminated before this part was reached)
Blood and lymphatic system disorders Decreased white count	11.1% 1/9 • Adverse events were collected after the first dose until end of treatment, death, or loss to follow up, maximum 18 months Part 2 Tumor-specific expansion (trial was terminated before this part was reached)	— 0/0 • Adverse events were collected after the first dose until end of treatment, death, or loss to follow up, maximum 18 months Part 2 Tumor-specific expansion (trial was terminated before this part was reached)
Gastrointestinal disorders AST	11.1% 1/9 • Adverse events were collected after the first dose until end of treatment, death, or loss to follow up, maximum 18 months Part 2 Tumor-specific expansion (trial was terminated before this part was reached)	— 0/0 • Adverse events were collected after the first dose until end of treatment, death, or loss to follow up, maximum 18 months Part 2 Tumor-specific expansion (trial was terminated before this part was reached)
Gastrointestinal disorders Bilirubin	11.1% 1/9 • Adverse events were collected after the first dose until end of treatment, death, or loss to follow up, maximum 18 months Part 2 Tumor-specific expansion (trial was terminated before this part was reached)	— 0/0 • Adverse events were collected after the first dose until end of treatment, death, or loss to follow up, maximum 18 months Part 2 Tumor-specific expansion (trial was terminated before this part was reached)
General disorders Knee pain	11.1% 1/9 • Adverse events were collected after the first dose until end of treatment, death, or loss to follow up, maximum 18 months Part 2 Tumor-specific expansion (trial was terminated before this part was reached)	— 0/0 • Adverse events were collected after the first dose until end of treatment, death, or loss to follow up, maximum 18 months Part 2 Tumor-specific expansion (trial was terminated before this part was reached)
Skin and subcutaneous tissue disorders Change of skin sensitivity	11.1% 1/9 • Adverse events were collected after the first dose until end of treatment, death, or loss to follow up, maximum 18 months Part 2 Tumor-specific expansion (trial was terminated before this part was reached)	— 0/0 • Adverse events were collected after the first dose until end of treatment, death, or loss to follow up, maximum 18 months Part 2 Tumor-specific expansion (trial was terminated before this part was reached)
Respiratory, thoracic and mediastinal disorders Low ANC	11.1% 1/9 • Adverse events were collected after the first dose until end of treatment, death, or loss to follow up, maximum 18 months Part 2 Tumor-specific expansion (trial was terminated before this part was reached)	— 0/0 • Adverse events were collected after the first dose until end of treatment, death, or loss to follow up, maximum 18 months Part 2 Tumor-specific expansion (trial was terminated before this part was reached)
Respiratory, thoracic and mediastinal disorders Dyspnea	11.1% 1/9 • Adverse events were collected after the first dose until end of treatment, death, or loss to follow up, maximum 18 months Part 2 Tumor-specific expansion (trial was terminated before this part was reached)	— 0/0 • Adverse events were collected after the first dose until end of treatment, death, or loss to follow up, maximum 18 months Part 2 Tumor-specific expansion (trial was terminated before this part was reached)
Respiratory, thoracic and mediastinal disorders Non-cardiac chest pain	11.1% 1/9 • Adverse events were collected after the first dose until end of treatment, death, or loss to follow up, maximum 18 months Part 2 Tumor-specific expansion (trial was terminated before this part was reached)	— 0/0 • Adverse events were collected after the first dose until end of treatment, death, or loss to follow up, maximum 18 months Part 2 Tumor-specific expansion (trial was terminated before this part was reached)
Respiratory, thoracic and mediastinal disorders Pneumothorax	11.1% 1/9 • Adverse events were collected after the first dose until end of treatment, death, or loss to follow up, maximum 18 months Part 2 Tumor-specific expansion (trial was terminated before this part was reached)	— 0/0 • Adverse events were collected after the first dose until end of treatment, death, or loss to follow up, maximum 18 months Part 2 Tumor-specific expansion (trial was terminated before this part was reached)

Additional Information

Dr. David Hong

M D Anderson Cancer Center

Phone: (713) 563-5844

Email: dshong@mdanderson.org

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place