Trial Outcomes & Findings for Tipifarnib in Advanced Squamous NSCLC With Oncogen HRAS MutAtionS (NCT NCT03496766)
NCT ID: NCT03496766
Last Updated: 2025-03-05
Results Overview
To determine the antitumor activity in terms of objective response rate (ORR) of tipifarnib in subjects with locally advanced unresectable or metastatic, relapsed and/or refractory, squamous non-small cell lung cancer (SQ-NSCLC) with HRAS mutations. Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR. Progressive disease (PD): at least a 20% increase in the sum of diameters of target lesions.
Recruitment status
TERMINATED
Study phase
PHASE2
Target enrollment
9 participants
Primary outcome timeframe
From the first dose until progression disease, assessed from the first dose until the first assessment at week 6 from the first dose
Results posted on
2025-03-05
Participant Flow
Participant milestones
| Measure |
Experimental Arm
Tipifarnib 600 mg, po, bid daily on days 1-7 and 15-21 of 28-day treatment cycles for up to 24 months
Tipifarnib: Tipifarnib 600 mg will be administered until progression
|
|---|---|
|
Overall Study
STARTED
|
9
|
|
Overall Study
COMPLETED
|
9
|
|
Overall Study
NOT COMPLETED
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
One subject didn't receive 2nd line of antineoplastic treatment
Baseline characteristics by cohort
| Measure |
Experimental Arm
n=9 Participants
Tipifarnib 600 mg, po, bid daily on days 1-7 and 15-21 of 28-day treatment cycles for up to 24 months
Tipifarnib: Tipifarnib 600 mg will be administered until progression
|
|---|---|
|
Age, Continuous
|
68.8 years
STANDARD_DEVIATION 5.4 • n=9 Participants
|
|
Sex: Female, Male
Female
|
1 Participants
n=9 Participants
|
|
Sex: Female, Male
Male
|
8 Participants
n=9 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=9 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=9 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=9 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=9 Participants
|
|
Race (NIH/OMB)
White
|
9 Participants
n=9 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=9 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=9 Participants
|
|
Region of Enrollment
Spain
|
9 participants
n=9 Participants
|
|
Cigarette Smoking History
Never smoker (<= 100 cigarettes/lifetime)
|
0 Participants
n=9 Participants
|
|
Cigarette Smoking History
Former smoker (>= 1 year)
|
5 Participants
n=9 Participants
|
|
Cigarette Smoking History
Active smoker
|
4 Participants
n=9 Participants
|
|
ECOG Performance status
ECOG 0
|
0 Participants
n=9 Participants
|
|
ECOG Performance status
ECOG 1
|
9 Participants
n=9 Participants
|
|
ECOG Performance status
ECOG 2
|
0 Participants
n=9 Participants
|
|
ECOG Performance status
ECOG 3
|
0 Participants
n=9 Participants
|
|
ECOG Performance status
ECOG 4
|
0 Participants
n=9 Participants
|
|
Pulse rate
|
88.8 bpm
STANDARD_DEVIATION 12.1 • n=9 Participants
|
|
Systolic Blood Pressure
|
121.8 mmHg
STANDARD_DEVIATION 22.2 • n=9 Participants
|
|
Diastolic Blood Pressure
|
73.2 mmHg
STANDARD_DEVIATION 10.4 • n=9 Participants
|
|
Clinical Stage at inclusion
IIIB-IIIC
|
1 Participants
n=9 Participants
|
|
Clinical Stage at inclusion
IVA
|
4 Participants
n=9 Participants
|
|
Clinical Stage at inclusion
IVB
|
4 Participants
n=9 Participants
|
|
Prior Therapy Best Response
Partial Response
|
3 Participants
n=9 Participants
|
|
Prior Therapy Best Response
Stable Disease
|
4 Participants
n=9 Participants
|
|
Prior Therapy Best Response
Progression Disease
|
2 Participants
n=9 Participants
|
|
Antineoplastic TMT Chemotherapy First Line
Carboplatin
|
1 Participants
n=9 Participants
|
|
Antineoplastic TMT Chemotherapy First Line
Cisplatin
|
2 Participants
n=9 Participants
|
|
Antineoplastic TMT Chemotherapy First Line
Cisplatin + Gemcitabine
|
1 Participants
n=9 Participants
|
|
Antineoplastic TMT Chemotherapy First Line
Paclitaxel
|
1 Participants
n=9 Participants
|
|
Antineoplastic TMT Chemotherapy First Line
Pembrolizumab
|
3 Participants
n=9 Participants
|
|
Antineoplastic TMT Chemotherapy First Line
Carboplatin + Pemetrexed + Pembrolizumab
|
1 Participants
n=9 Participants
|
|
Antineoplastic TMT Chemotherapy Second Line
Carboplatin
|
1 Participants
n=8 Participants • One subject didn't receive 2nd line of antineoplastic treatment
|
|
Antineoplastic TMT Chemotherapy Second Line
Carboplatin + Gemcitabine
|
1 Participants
n=8 Participants • One subject didn't receive 2nd line of antineoplastic treatment
|
|
Antineoplastic TMT Chemotherapy Second Line
Carboplatin + Vinorebine
|
1 Participants
n=8 Participants • One subject didn't receive 2nd line of antineoplastic treatment
|
|
Antineoplastic TMT Chemotherapy Second Line
Cisplatin + Gemcitabine
|
1 Participants
n=8 Participants • One subject didn't receive 2nd line of antineoplastic treatment
|
|
Antineoplastic TMT Chemotherapy Second Line
Gemcitabine
|
1 Participants
n=8 Participants • One subject didn't receive 2nd line of antineoplastic treatment
|
|
Antineoplastic TMT Chemotherapy Second Line
Paclitaxel
|
2 Participants
n=8 Participants • One subject didn't receive 2nd line of antineoplastic treatment
|
|
Antineoplastic TMT Chemotherapy Second Line
Pembrolizumab + Radium 223
|
1 Participants
n=8 Participants • One subject didn't receive 2nd line of antineoplastic treatment
|
|
Antineoplastic TMT Chemotherapy Third Line
Carboplatin
|
1 Participants
n=3 Participants • 6 subject didn't receive 3rd line of antineoplastic treatment
|
|
Antineoplastic TMT Chemotherapy Third Line
Cetuximab
|
1 Participants
n=3 Participants • 6 subject didn't receive 3rd line of antineoplastic treatment
|
|
Antineoplastic TMT Chemotherapy Third Line
Docetaxel
|
1 Participants
n=3 Participants • 6 subject didn't receive 3rd line of antineoplastic treatment
|
|
Antineoplastic TMT Chemotherapy Fourth Line
Avelumab
|
1 Participants
n=2 Participants • 7 subject didn't receive 4 line of antineoplastic treatment
|
|
Antineoplastic TMT Chemotherapy Fourth Line
Nivolumab
|
1 Participants
n=2 Participants • 7 subject didn't receive 4 line of antineoplastic treatment
|
|
Antineoplastic TMT Chemotherapy Fifth Line
Docetaxel
|
1 Participants
n=2 Participants • 7 subject didn't receive 5th line of antineoplastic treatment
|
|
Antineoplastic TMT Chemotherapy Fifth Line
Etoposide
|
1 Participants
n=2 Participants • 7 subject didn't receive 5th line of antineoplastic treatment
|
PRIMARY outcome
Timeframe: From the first dose until progression disease, assessed from the first dose until the first assessment at week 6 from the first dosePopulation: Per protocol population
To determine the antitumor activity in terms of objective response rate (ORR) of tipifarnib in subjects with locally advanced unresectable or metastatic, relapsed and/or refractory, squamous non-small cell lung cancer (SQ-NSCLC) with HRAS mutations. Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR. Progressive disease (PD): at least a 20% increase in the sum of diameters of target lesions.
Outcome measures
| Measure |
Experimental Arm
n=6 Participants
Tipifarnib 600 mg, po, bid daily on days 1-7 and 15-21 of 28-day treatment cycles for up to 24 months
Tipifarnib: Tipifarnib 600 mg will be administered until progression
|
|---|---|
|
Overall Response
Stable Disease
|
2 Participants
|
|
Overall Response
Progression Disease
|
4 Participants
|
SECONDARY outcome
Timeframe: From the start of treatment until first progression or death.Defined as the time from the start date of treatment TMT as the origin of follow-up and the first progression or death as final date.
Outcome measures
| Measure |
Experimental Arm
n=9 Participants
Tipifarnib 600 mg, po, bid daily on days 1-7 and 15-21 of 28-day treatment cycles for up to 24 months
Tipifarnib: Tipifarnib 600 mg will be administered until progression
|
|---|---|
|
Progression Free Survival
|
8.6 months
Standard Deviation 18.7
|
SECONDARY outcome
Timeframe: From the date of randomization until end of follow up,up to 24 monthsDefined as the length of time from either the date of diagnosis or the start of the treatment that patients diagnosed with the disease are still alive.
Outcome measures
| Measure |
Experimental Arm
n=9 Participants
Tipifarnib 600 mg, po, bid daily on days 1-7 and 15-21 of 28-day treatment cycles for up to 24 months
Tipifarnib: Tipifarnib 600 mg will be administered until progression
|
|---|---|
|
Overall Survival
|
12.4 Months
Interval 9.7 to 21.7
|
Adverse Events
Experimental Arm
Serious events: 9 serious events
Other events: 9 other events
Deaths: 9 deaths
Serious adverse events
| Measure |
Experimental Arm
n=9 participants at risk
Tipifarnib 600 mg, po, bid daily on days 1-7 and 15-21 of 28-day treatment cycles for up to 24 months
Tipifarnib: Tipifarnib 600 mg will be administered until progression
|
|---|---|
|
Renal and urinary disorders
Renal and urinary disorders
|
66.7%
6/9 • Number of events 6 • 25 months
The severity of AE will be determined using CTCA version 4
|
|
Renal and urinary disorders
Acute kidney injury
|
11.1%
1/9 • Number of events 1 • 25 months
The severity of AE will be determined using CTCA version 4
|
|
General disorders
Fatigue
|
11.1%
1/9 • Number of events 1 • 25 months
The severity of AE will be determined using CTCA version 4
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
22.2%
2/9 • Number of events 2 • 25 months
The severity of AE will be determined using CTCA version 4
|
|
Blood and lymphatic system disorders
Platelet count decreased
|
22.2%
2/9 • Number of events 2 • 25 months
The severity of AE will be determined using CTCA version 4
|
|
Nervous system disorders
Nervous system disorders
|
11.1%
1/9 • Number of events 1 • 25 months
The severity of AE will be determined using CTCA version 4
|
|
Blood and lymphatic system disorders
Thromboembolic event
|
11.1%
1/9 • Number of events 1 • 25 months
The severity of AE will be determined using CTCA version 4
|
|
Infections and infestations
Sepsis
|
11.1%
1/9 • Number of events 1 • 25 months
The severity of AE will be determined using CTCA version 4
|
Other adverse events
| Measure |
Experimental Arm
n=9 participants at risk
Tipifarnib 600 mg, po, bid daily on days 1-7 and 15-21 of 28-day treatment cycles for up to 24 months
Tipifarnib: Tipifarnib 600 mg will be administered until progression
|
|---|---|
|
Blood and lymphatic system disorders
Anemia
|
100.0%
9/9 • Number of events 9 • 25 months
The severity of AE will be determined using CTCA version 4
|
|
Investigations
Hyperglycemia
|
77.8%
7/9 • Number of events 7 • 25 months
The severity of AE will be determined using CTCA version 4
|
|
General disorders
Confusion
|
11.1%
1/9 • Number of events 1 • 25 months
The severity of AE will be determined using CTCA version 4
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place