Trial Outcomes & Findings for Tucatinib, Palbociclib and Letrozole in Metastatic Hormone Receptor Positive and HER2-positive Breast Cancer (NCT NCT03054363)
NCT ID: NCT03054363
Last Updated: 2023-11-13
Results Overview
To measure safety and tolerability of tucatinib used in combination with palbociclib and letrozole, we will assess the proportion of subjects experiencing dose-limiting toxicities (DLTs) potentially attributable to tucatinib, palbociclib, or both drugs, and compare them to predefined safety thresholds. DLT was defined as any grade ≥ 3 nonhematologic adverse event, grade 3 neutropenia with fever, grade 3 thrombocytopenia with bleeding, or any hematologic toxicity grade ≥ 4 using NCI CTCAE version 4.03. Safety was considered clinically meaningfully altered if ≥60% of subjects experienced DLTs secondary palbociclib, ≥20% of subjects had toxicity secondary to tucatinib, or ≥50% of subjects had DLTs attributable to both drugs. If the proportion of patients with DLTs cross safety boundaries, doses of tucatinib, palbociclib or both medications would be decreased. Letrozole dose was kept constant for all study subjects.
Recruitment status
COMPLETED
Study phase
PHASE1/PHASE2
Target enrollment
42 participants
Primary outcome timeframe
15 months (From date of first consent until final safety analysis of Phase Ib)
Results posted on
2023-11-13
Participant Flow
Participant milestones
| Measure |
Phase 1b
Tucatinib in Combination with Palbociclib and Letrozole (Safety Cohort): Starting dose of combination therapy :
Tucatinib 300 mg PO BID Palbociclib 125 mg PO daily 21 day on, 7 days off Letrozole 2.5 mg PO daily
|
Phase II
The study completed the final phase Ib safety analysis on January 31, 2019. Tucatinib 300 mg BID; palbociclib 75 mg PO daily 21 days on, 7 days off; letrozole 2.5 mg PO daily..
|
|---|---|---|
|
Overall Study
STARTED
|
20
|
22
|
|
Overall Study
COMPLETED
|
20
|
22
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Tucatinib, Palbociclib and Letrozole in Metastatic Hormone Receptor Positive and HER2-positive Breast Cancer
Baseline characteristics by cohort
| Measure |
Phase Ib
n=20 Participants
Tucatinib 300 mg PO BID Ppalbociclib 125 mg PO daily 21 days on and 7 days off Letrozole 2.5 mg PO daily on a 28 day cycle length.
|
Phase II
n=22 Participants
Tucatinib 300 mg PO BID Palbociclib 75mg PO daily 21 days on followed by 7 days off Letrozole 2.5 mg PO daily.
|
Total
n=42 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
17 Participants
n=93 Participants
|
16 Participants
n=4 Participants
|
33 Participants
n=27 Participants
|
|
Age, Categorical
>=65 years
|
3 Participants
n=93 Participants
|
6 Participants
n=4 Participants
|
9 Participants
n=27 Participants
|
|
Age, Continuous
|
51 years
STANDARD_DEVIATION 11.55 • n=93 Participants
|
53.12 years
STANDARD_DEVIATION 15.49 • n=4 Participants
|
51.91 years
STANDARD_DEVIATION 13.60 • n=27 Participants
|
|
Sex: Female, Male
Female
|
20 Participants
n=93 Participants
|
22 Participants
n=4 Participants
|
42 Participants
n=27 Participants
|
|
Sex: Female, Male
Male
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
6 Participants
n=93 Participants
|
5 Participants
n=4 Participants
|
11 Participants
n=27 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
14 Participants
n=93 Participants
|
17 Participants
n=4 Participants
|
31 Participants
n=27 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=93 Participants
|
1 Participants
n=4 Participants
|
1 Participants
n=27 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Race (NIH/OMB)
Black or African American
|
1 Participants
n=93 Participants
|
1 Participants
n=4 Participants
|
2 Participants
n=27 Participants
|
|
Race (NIH/OMB)
White
|
19 Participants
n=93 Participants
|
18 Participants
n=4 Participants
|
37 Participants
n=27 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=93 Participants
|
1 Participants
n=4 Participants
|
1 Participants
n=27 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=93 Participants
|
1 Participants
n=4 Participants
|
1 Participants
n=27 Participants
|
|
Region of Enrollment
United States
|
20 participants
n=93 Participants
|
22 participants
n=4 Participants
|
42 participants
n=27 Participants
|
PRIMARY outcome
Timeframe: 15 months (From date of first consent until final safety analysis of Phase Ib)Population: Among the 20 phase Ib patients, 1 (5%) had a dose reduction of tucatinib, and 9 (45%) had a dose reduction of palbociclib for DLTs. Two patients (10%) discontinued palbociclib because of DLTs (neutropenia) and continued tucatinib and letrozole. One patient (5%) discontinued letrozole for toxicity, and continued tucatinib and palbociclib. The pre-defined safety boundaries were not crossed.
To measure safety and tolerability of tucatinib used in combination with palbociclib and letrozole, we will assess the proportion of subjects experiencing dose-limiting toxicities (DLTs) potentially attributable to tucatinib, palbociclib, or both drugs, and compare them to predefined safety thresholds. DLT was defined as any grade ≥ 3 nonhematologic adverse event, grade 3 neutropenia with fever, grade 3 thrombocytopenia with bleeding, or any hematologic toxicity grade ≥ 4 using NCI CTCAE version 4.03. Safety was considered clinically meaningfully altered if ≥60% of subjects experienced DLTs secondary palbociclib, ≥20% of subjects had toxicity secondary to tucatinib, or ≥50% of subjects had DLTs attributable to both drugs. If the proportion of patients with DLTs cross safety boundaries, doses of tucatinib, palbociclib or both medications would be decreased. Letrozole dose was kept constant for all study subjects.
Outcome measures
| Measure |
Baseline Starting Dose Patients for Phase Ib (Tucatinib 300mg, Palbociclib 125mg, Letrozole 2.5mg)
n=20 Participants
Enroll 10 subjects at the baseline starting doses (DL1) of tucatinib 300 mg PO BID, palbociclib 125 mg PO daily 21 days on and 7 days off, and letrozole 2.5 mg PO daily on a 28 day cycle length. After 10 subjects are accrued to the study and complete at least 1 cycle of treatment, an interim analysis of the safety phase Ib cohort will be done.
Plan - 10 subjects enrolled, completed at least one cycle of treatment (28 days) and evaluable for safety analysis: If there are 7 or fewer subjects experience DLTs due to palbociclib, 3 or fewer subjects experience DLTs due to tucatinib, and 7 or fewer subjects experience DLTs potentially attributable to both drugs, then the interim safety of the Phase Ib cohort will be considered acceptable and accrual will continue to enroll to 20 subjects without change of the starting doses.
Tucatinib in Combination with Palbociclib and Letrozole (Safety Cohort): Starting dose of combination therapy :
Tucatinib 300 mg PO BID Palbociclib 125 mg PO daily 21 day on, 7 days off Letrozole 2.5 mg PO daily
|
Dose-reduced Patients for Phase II (Tucatinib 300mg, Palbociclib 75mg, Letrozole 2.5mg)
n=13 Participants
Patients who participated in the phase Ib part of the study and continued into the phase II part and had their palbociclib dose reduced.
|
Overall Patient Cohort
n=20 Participants
All patients from both parts of the study.
|
|---|---|---|---|
|
Phase Ib Primary Outcome: Proportion of Patients Who Experienced DLTs Attributable to Palbociclib, Tucatinib, or Both
|
100 percentage of participants
|
65 percentage of participants
|
100 percentage of participants
|
PRIMARY outcome
Timeframe: 4 years (data cutoff of PFS calculation was when PFS became mature according to study statistician)Population: There were 40 evaluable patients for this efficacy outcome. Two patients were non-evaluable because they received less than 2 cycles of treatment.
To measure efficacy of tucatinib used in combination with palbociclib and letrozole, the median PFS (primary objective of Phase II) will be assessed. mPFS is defined as the time from allocation to the first documented disease progression according to RECIST 1.1, or death due to any cause, whichever occurs first. For subjects with brain metastatic disease enrolled in the study, assessment of bi-compartmental mPFS in the non-CNS and CNS compartments, defined as the time from allocation to the first documented disease progression according to RECIST 1.1 and/or RANO-BM criteria, or death due to any cause, whichever occurs first. For patient with CNS metastases who had an event of isolated CNS progression, underwent local therapy, and remained on study per protocol, mPFS was calculated as the time from the start of treatment until the first CNS progression.
Outcome measures
| Measure |
Baseline Starting Dose Patients for Phase Ib (Tucatinib 300mg, Palbociclib 125mg, Letrozole 2.5mg)
n=40 Participants
Enroll 10 subjects at the baseline starting doses (DL1) of tucatinib 300 mg PO BID, palbociclib 125 mg PO daily 21 days on and 7 days off, and letrozole 2.5 mg PO daily on a 28 day cycle length. After 10 subjects are accrued to the study and complete at least 1 cycle of treatment, an interim analysis of the safety phase Ib cohort will be done.
Plan - 10 subjects enrolled, completed at least one cycle of treatment (28 days) and evaluable for safety analysis: If there are 7 or fewer subjects experience DLTs due to palbociclib, 3 or fewer subjects experience DLTs due to tucatinib, and 7 or fewer subjects experience DLTs potentially attributable to both drugs, then the interim safety of the Phase Ib cohort will be considered acceptable and accrual will continue to enroll to 20 subjects without change of the starting doses.
Tucatinib in Combination with Palbociclib and Letrozole (Safety Cohort): Starting dose of combination therapy :
Tucatinib 300 mg PO BID Palbociclib 125 mg PO daily 21 day on, 7 days off Letrozole 2.5 mg PO daily
|
Dose-reduced Patients for Phase II (Tucatinib 300mg, Palbociclib 75mg, Letrozole 2.5mg)
n=15 Participants
Patients who participated in the phase Ib part of the study and continued into the phase II part and had their palbociclib dose reduced.
|
Overall Patient Cohort
n=25 Participants
All patients from both parts of the study.
|
|---|---|---|---|
|
Phase II Primary Outcome: Median Progression-free Survival (mPFS)
|
8.4 months
Interval 6.6 to 10.8
|
8.2 months
Interval 5.4 to 20.1
|
10.0 months
Interval 7.2 to 14.9
|
SECONDARY outcome
Timeframe: 0, 0.5, 1, 2, 3, 4, and 6 hours post-dosePopulation: All 20 patients enrolled in Phase Ib were included in PK analysis.
Pharmacokinetic (PK) assessments of blood levels of tucatinib and palbociclib will be performed on Cycle 1 Day 15 and Cycle 2 Day 1 of therapy in 20 participants enrolled in the phase Ib part of the study. Plasma samples will be collected to measure levels of tucatinib and its hydroxyl metabolite ONT-993, as well as levels of palbociclib and, if needed, its metabolites at steady state on Cycle 1 Day 15. The area under the curve (AUC) of the concentration vs. time plot is computed from 0 to 6 hours after the tucatinib and palbociclib dose.
Outcome measures
| Measure |
Baseline Starting Dose Patients for Phase Ib (Tucatinib 300mg, Palbociclib 125mg, Letrozole 2.5mg)
n=20 Participants
Enroll 10 subjects at the baseline starting doses (DL1) of tucatinib 300 mg PO BID, palbociclib 125 mg PO daily 21 days on and 7 days off, and letrozole 2.5 mg PO daily on a 28 day cycle length. After 10 subjects are accrued to the study and complete at least 1 cycle of treatment, an interim analysis of the safety phase Ib cohort will be done.
Plan - 10 subjects enrolled, completed at least one cycle of treatment (28 days) and evaluable for safety analysis: If there are 7 or fewer subjects experience DLTs due to palbociclib, 3 or fewer subjects experience DLTs due to tucatinib, and 7 or fewer subjects experience DLTs potentially attributable to both drugs, then the interim safety of the Phase Ib cohort will be considered acceptable and accrual will continue to enroll to 20 subjects without change of the starting doses.
Tucatinib in Combination with Palbociclib and Letrozole (Safety Cohort): Starting dose of combination therapy :
Tucatinib 300 mg PO BID Palbociclib 125 mg PO daily 21 day on, 7 days off Letrozole 2.5 mg PO daily
|
Dose-reduced Patients for Phase II (Tucatinib 300mg, Palbociclib 75mg, Letrozole 2.5mg)
Patients who participated in the phase Ib part of the study and continued into the phase II part and had their palbociclib dose reduced.
|
Overall Patient Cohort
All patients from both parts of the study.
|
|---|---|---|---|
|
Phase Ib Secondary Outcome: Tucatinib and Palbociclib AUC[0-6] Post Tucatinib and Palbociclib Dose
Palbociclib
|
647 h*ng/mL
Interval 183.6 to 1983.0
|
—
|
—
|
|
Phase Ib Secondary Outcome: Tucatinib and Palbociclib AUC[0-6] Post Tucatinib and Palbociclib Dose
Tucatinib
|
2433 h*ng/mL
Interval 1289.0 to 4022.0
|
—
|
—
|
|
Phase Ib Secondary Outcome: Tucatinib and Palbociclib AUC[0-6] Post Tucatinib and Palbociclib Dose
ONT-993 (Tucatinib metabolite)
|
340 h*ng/mL
Interval 156.5 to 943.1
|
—
|
—
|
SECONDARY outcome
Timeframe: 10, 13, 16, and 19 hours post-dosePopulation: 9 patients were studied for Phase II PKs.
Additional pharmacokinetic (PK) assessment will be done in 5 to 10 patients enrolled in phase II part of the study to evaluate the levels of tucatinib and palbociclib. These PKs will be done on Cycle 1 Day 9 and Cycle 2 Day 9. Prior to the first set of PKs, on Cycle 1 Days 1-8, patient will take palbociclib and letrozole; tucatinib will be on hold. Tucatinib will be started per usual study schedule after the first set of PKs is obtained on Day 9. Prior to the second set of PKs, on Cycle 2 Days 1-8, patient will take palbociclib, letrozole and tucatinib (all study drugs) per usual study schedule. On the day prior to PK evaluation (Day 8 of Cycle 1 and Day 8 of Cycle 2), patient should consume high calorie / high fat meal and take study drugs. On the next day, plasma samples will be collected to measure PKs at 10, 13, 16 and 19 hrs +/- 10 minutes post dose.
Outcome measures
| Measure |
Baseline Starting Dose Patients for Phase Ib (Tucatinib 300mg, Palbociclib 125mg, Letrozole 2.5mg)
n=9 Participants
Enroll 10 subjects at the baseline starting doses (DL1) of tucatinib 300 mg PO BID, palbociclib 125 mg PO daily 21 days on and 7 days off, and letrozole 2.5 mg PO daily on a 28 day cycle length. After 10 subjects are accrued to the study and complete at least 1 cycle of treatment, an interim analysis of the safety phase Ib cohort will be done.
Plan - 10 subjects enrolled, completed at least one cycle of treatment (28 days) and evaluable for safety analysis: If there are 7 or fewer subjects experience DLTs due to palbociclib, 3 or fewer subjects experience DLTs due to tucatinib, and 7 or fewer subjects experience DLTs potentially attributable to both drugs, then the interim safety of the Phase Ib cohort will be considered acceptable and accrual will continue to enroll to 20 subjects without change of the starting doses.
Tucatinib in Combination with Palbociclib and Letrozole (Safety Cohort): Starting dose of combination therapy :
Tucatinib 300 mg PO BID Palbociclib 125 mg PO daily 21 day on, 7 days off Letrozole 2.5 mg PO daily
|
Dose-reduced Patients for Phase II (Tucatinib 300mg, Palbociclib 75mg, Letrozole 2.5mg)
Patients who participated in the phase Ib part of the study and continued into the phase II part and had their palbociclib dose reduced.
|
Overall Patient Cohort
All patients from both parts of the study.
|
|---|---|---|---|
|
Phase II Secondary Outcome: Palbociclib AUC[10-19] Post Tucatinib and Palbociclib Dose
|
656 h*ng/mL
Interval 506.0 to 1108.0
|
—
|
—
|
SECONDARY outcome
Timeframe: 4 yearsPopulation: 27 patients of the 40 who were evaluable for safety were analyzable for this tumor response outcome because they had measurable lesions.
Clinical benefit rate (CBR) was assessed in patients with measurable lesions and defined as the proportion of patients with complete response, partial response, or stable disease for 6 months or more. It is one of the parameters used to assess tumor response in this study and was evaluated using RECIST 1.1 (and/or RANO-BM for patients with CNS disease).
Outcome measures
| Measure |
Baseline Starting Dose Patients for Phase Ib (Tucatinib 300mg, Palbociclib 125mg, Letrozole 2.5mg)
n=27 Participants
Enroll 10 subjects at the baseline starting doses (DL1) of tucatinib 300 mg PO BID, palbociclib 125 mg PO daily 21 days on and 7 days off, and letrozole 2.5 mg PO daily on a 28 day cycle length. After 10 subjects are accrued to the study and complete at least 1 cycle of treatment, an interim analysis of the safety phase Ib cohort will be done.
Plan - 10 subjects enrolled, completed at least one cycle of treatment (28 days) and evaluable for safety analysis: If there are 7 or fewer subjects experience DLTs due to palbociclib, 3 or fewer subjects experience DLTs due to tucatinib, and 7 or fewer subjects experience DLTs potentially attributable to both drugs, then the interim safety of the Phase Ib cohort will be considered acceptable and accrual will continue to enroll to 20 subjects without change of the starting doses.
Tucatinib in Combination with Palbociclib and Letrozole (Safety Cohort): Starting dose of combination therapy :
Tucatinib 300 mg PO BID Palbociclib 125 mg PO daily 21 day on, 7 days off Letrozole 2.5 mg PO daily
|
Dose-reduced Patients for Phase II (Tucatinib 300mg, Palbociclib 75mg, Letrozole 2.5mg)
Patients who participated in the phase Ib part of the study and continued into the phase II part and had their palbociclib dose reduced.
|
Overall Patient Cohort
All patients from both parts of the study.
|
|---|---|---|---|
|
Phase II Secondary Outcome: Clinical Benefit Rate (CBR)
|
70.4 percentage of participants
|
—
|
—
|
SECONDARY outcome
Timeframe: 4 yearsPopulation: 27 patients of the 40 who were evaluable for safety were analyzable for this tumor response outcome because they had measurable lesions.
Overall response rate (ORR) is defined as the proportion of subjects who had complete or partial response by RECIST 1.1 (and/or RANO-BM for patients with CNS disease).
Outcome measures
| Measure |
Baseline Starting Dose Patients for Phase Ib (Tucatinib 300mg, Palbociclib 125mg, Letrozole 2.5mg)
n=27 Participants
Enroll 10 subjects at the baseline starting doses (DL1) of tucatinib 300 mg PO BID, palbociclib 125 mg PO daily 21 days on and 7 days off, and letrozole 2.5 mg PO daily on a 28 day cycle length. After 10 subjects are accrued to the study and complete at least 1 cycle of treatment, an interim analysis of the safety phase Ib cohort will be done.
Plan - 10 subjects enrolled, completed at least one cycle of treatment (28 days) and evaluable for safety analysis: If there are 7 or fewer subjects experience DLTs due to palbociclib, 3 or fewer subjects experience DLTs due to tucatinib, and 7 or fewer subjects experience DLTs potentially attributable to both drugs, then the interim safety of the Phase Ib cohort will be considered acceptable and accrual will continue to enroll to 20 subjects without change of the starting doses.
Tucatinib in Combination with Palbociclib and Letrozole (Safety Cohort): Starting dose of combination therapy :
Tucatinib 300 mg PO BID Palbociclib 125 mg PO daily 21 day on, 7 days off Letrozole 2.5 mg PO daily
|
Dose-reduced Patients for Phase II (Tucatinib 300mg, Palbociclib 75mg, Letrozole 2.5mg)
Patients who participated in the phase Ib part of the study and continued into the phase II part and had their palbociclib dose reduced.
|
Overall Patient Cohort
All patients from both parts of the study.
|
|---|---|---|---|
|
Phase II Secondary Outcome: Overall Response Rate (ORR)
|
44.5 percentage of participants
|
—
|
—
|
SECONDARY outcome
Timeframe: 4 yearsPopulation: 27 patients of the 40 who were evaluable for safety were analyzable for this tumor response outcome because they had measurable lesions.
Median duration of response (mDOR) is defined as the time from enrollment in the clinical trial until objective tumor progression or death, whichever occurs first.
Outcome measures
| Measure |
Baseline Starting Dose Patients for Phase Ib (Tucatinib 300mg, Palbociclib 125mg, Letrozole 2.5mg)
n=27 Participants
Enroll 10 subjects at the baseline starting doses (DL1) of tucatinib 300 mg PO BID, palbociclib 125 mg PO daily 21 days on and 7 days off, and letrozole 2.5 mg PO daily on a 28 day cycle length. After 10 subjects are accrued to the study and complete at least 1 cycle of treatment, an interim analysis of the safety phase Ib cohort will be done.
Plan - 10 subjects enrolled, completed at least one cycle of treatment (28 days) and evaluable for safety analysis: If there are 7 or fewer subjects experience DLTs due to palbociclib, 3 or fewer subjects experience DLTs due to tucatinib, and 7 or fewer subjects experience DLTs potentially attributable to both drugs, then the interim safety of the Phase Ib cohort will be considered acceptable and accrual will continue to enroll to 20 subjects without change of the starting doses.
Tucatinib in Combination with Palbociclib and Letrozole (Safety Cohort): Starting dose of combination therapy :
Tucatinib 300 mg PO BID Palbociclib 125 mg PO daily 21 day on, 7 days off Letrozole 2.5 mg PO daily
|
Dose-reduced Patients for Phase II (Tucatinib 300mg, Palbociclib 75mg, Letrozole 2.5mg)
Patients who participated in the phase Ib part of the study and continued into the phase II part and had their palbociclib dose reduced.
|
Overall Patient Cohort
All patients from both parts of the study.
|
|---|---|---|---|
|
Phase II Secondary Outcome: Median Duration of Response (mDOR)
|
13.9 months
Interval 5.51 to 31.8
|
—
|
—
|
Adverse Events
Phase Ib
Serious events: 9 serious events
Other events: 20 other events
Deaths: 0 deaths
Phase II
Serious events: 7 serious events
Other events: 22 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Phase Ib
n=20 participants at risk
Tucatinib 300 mg PO BID, palbociclib 125 mg PO daily 21 days on and 7 days off, and letrozole 2.5 mg PO daily on a 28 day cycle length.
|
Phase II
n=22 participants at risk
Tucatinib 300 mg BID; palbociclib 75 mg PO daily 21 days on, 7 days off; letrozole 2.5 mg PO daily.
|
|---|---|---|
|
Infections and infestations
Sepsis
|
5.0%
1/20 • Number of events 1 • Approximately 1 year
|
4.5%
1/22 • Number of events 3 • Approximately 1 year
|
|
Respiratory, thoracic and mediastinal disorders
Pleural Effusions, Bilateral
|
0.00%
0/20 • Approximately 1 year
|
4.5%
1/22 • Number of events 1 • Approximately 1 year
|
|
Infections and infestations
Appendicitis
|
0.00%
0/20 • Approximately 1 year
|
4.5%
1/22 • Number of events 1 • Approximately 1 year
|
|
Renal and urinary disorders
Hydronephrosis with Hydrourters, Bilateral
|
0.00%
0/20 • Approximately 1 year
|
4.5%
1/22 • Number of events 1 • Approximately 1 year
|
|
Nervous system disorders
Dizziness
|
0.00%
0/20 • Approximately 1 year
|
4.5%
1/22 • Number of events 1 • Approximately 1 year
|
|
Metabolism and nutrition disorders
Hypercalcemia
|
0.00%
0/20 • Approximately 1 year
|
4.5%
1/22 • Number of events 1 • Approximately 1 year
|
|
General disorders
Non-Cardiac Chest Pain
|
0.00%
0/20 • Approximately 1 year
|
4.5%
1/22 • Number of events 1 • Approximately 1 year
|
|
Respiratory, thoracic and mediastinal disorders
Upper respiratory infection, possible
|
0.00%
0/20 • Approximately 1 year
|
4.5%
1/22 • Number of events 1 • Approximately 1 year
|
|
General disorders
Malnutrition, Severe
|
0.00%
0/20 • Approximately 1 year
|
4.5%
1/22 • Number of events 1 • Approximately 1 year
|
|
Gastrointestinal disorders
Abdominal Distension
|
5.0%
1/20 • Number of events 1 • Approximately 1 year
|
0.00%
0/22 • Approximately 1 year
|
|
Gastrointestinal disorders
Abdominal Pain
|
5.0%
1/20 • Number of events 1 • Approximately 1 year
|
0.00%
0/22 • Approximately 1 year
|
|
Investigations
AST Increase
|
5.0%
1/20 • Number of events 1 • Approximately 1 year
|
0.00%
0/22 • Approximately 1 year
|
|
Investigations
ALT Increase
|
5.0%
1/20 • Number of events 1 • Approximately 1 year
|
0.00%
0/22 • Approximately 1 year
|
|
Gastrointestinal disorders
Constipation
|
5.0%
1/20 • Number of events 1 • Approximately 1 year
|
0.00%
0/22 • Approximately 1 year
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
5.0%
1/20 • Number of events 1 • Approximately 1 year
|
0.00%
0/22 • Approximately 1 year
|
|
Infections and infestations
Skin Infection
|
5.0%
1/20 • Number of events 1 • Approximately 1 year
|
0.00%
0/22 • Approximately 1 year
|
|
Respiratory, thoracic and mediastinal disorders
Lung Infection (Pneumonia)
|
5.0%
1/20 • Number of events 1 • Approximately 1 year
|
0.00%
0/22 • Approximately 1 year
|
|
Nervous system disorders
Migraine
|
5.0%
1/20 • Number of events 1 • Approximately 1 year
|
0.00%
0/22 • Approximately 1 year
|
|
General disorders
Pain
|
10.0%
2/20 • Number of events 2 • Approximately 1 year
|
0.00%
0/22 • Approximately 1 year
|
|
Vascular disorders
Thromboembolic Event, Pulmonary Embolism
|
5.0%
1/20 • Number of events 1 • Approximately 1 year
|
0.00%
0/22 • Approximately 1 year
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory Failure
|
5.0%
1/20 • Number of events 1 • Approximately 1 year
|
0.00%
0/22 • Approximately 1 year
|
|
Infections and infestations
Urinary Tract Infection
|
5.0%
1/20 • Number of events 1 • Approximately 1 year
|
0.00%
0/22 • Approximately 1 year
|
Other adverse events
| Measure |
Phase Ib
n=20 participants at risk
Tucatinib 300 mg PO BID, palbociclib 125 mg PO daily 21 days on and 7 days off, and letrozole 2.5 mg PO daily on a 28 day cycle length.
|
Phase II
n=22 participants at risk
Tucatinib 300 mg BID; palbociclib 75 mg PO daily 21 days on, 7 days off; letrozole 2.5 mg PO daily.
|
|---|---|---|
|
Gastrointestinal disorders
Abdominal Pain
|
25.0%
5/20 • Number of events 10 • Approximately 1 year
|
18.2%
4/22 • Number of events 4 • Approximately 1 year
|
|
Skin and subcutaneous tissue disorders
Acne (acneform rash)
|
10.0%
2/20 • Number of events 3 • Approximately 1 year
|
9.1%
2/22 • Number of events 2 • Approximately 1 year
|
|
Investigations
Activated Partial Thromboplastin Time Prolonged
|
10.0%
2/20 • Number of events 4 • Approximately 1 year
|
0.00%
0/22 • Approximately 1 year
|
|
General disorders
Adenopathy
|
5.0%
1/20 • Number of events 1 • Approximately 1 year
|
0.00%
0/22 • Approximately 1 year
|
|
Investigations
Alanine aminotransferase increased
|
15.0%
3/20 • Number of events 6 • Approximately 1 year
|
13.6%
3/22 • Number of events 5 • Approximately 1 year
|
|
Infections and infestations
Alkaline Phosphatase increased
|
10.0%
2/20 • Number of events 5 • Approximately 1 year
|
9.1%
2/22 • Number of events 2 • Approximately 1 year
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
25.0%
5/20 • Number of events 5 • Approximately 1 year
|
18.2%
4/22 • Number of events 4 • Approximately 1 year
|
|
Blood and lymphatic system disorders
Anemia
|
35.0%
7/20 • Number of events 16 • Approximately 1 year
|
13.6%
3/22 • Number of events 16 • Approximately 1 year
|
|
Metabolism and nutrition disorders
Anorexia
|
10.0%
2/20 • Number of events 2 • Approximately 1 year
|
22.7%
5/22 • Number of events 7 • Approximately 1 year
|
|
Musculoskeletal and connective tissue disorders
Arthralgias
|
15.0%
3/20 • Number of events 6 • Approximately 1 year
|
18.2%
4/22 • Number of events 7 • Approximately 1 year
|
|
Investigations
Aspartate Aminotransferase Increased
|
15.0%
3/20 • Number of events 8 • Approximately 1 year
|
13.6%
3/22 • Number of events 4 • Approximately 1 year
|
|
Infections and infestations
Pneumonia, Atypical
|
5.0%
1/20 • Number of events 1 • Approximately 1 year
|
4.5%
1/22 • Number of events 1 • Approximately 1 year
|
|
General disorders
Pain
|
60.0%
12/20 • Number of events 32 • Approximately 1 year
|
45.5%
10/22 • Number of events 18 • Approximately 1 year
|
|
Nervous system disorders
Tremors, Bilateral hands
|
5.0%
1/20 • Number of events 1 • Approximately 1 year
|
4.5%
1/22 • Number of events 1 • Approximately 1 year
|
|
Investigations
Bilirubin, Increased
|
10.0%
2/20 • Number of events 3 • Approximately 1 year
|
9.1%
2/22 • Number of events 3 • Approximately 1 year
|
|
Gastrointestinal disorders
Bloating
|
10.0%
2/20 • Number of events 3 • Approximately 1 year
|
0.00%
0/22 • Approximately 1 year
|
|
General disorders
Chills
|
20.0%
4/20 • Number of events 4 • Approximately 1 year
|
13.6%
3/22 • Number of events 3 • Approximately 1 year
|
|
Gastrointestinal disorders
Constipation
|
25.0%
5/20 • Number of events 5 • Approximately 1 year
|
18.2%
4/22 • Number of events 4 • Approximately 1 year
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
20.0%
4/20 • Number of events 4 • Approximately 1 year
|
18.2%
4/22 • Number of events 4 • Approximately 1 year
|
|
Renal and urinary disorders
Cystitis noninfective
|
5.0%
1/20 • Number of events 1 • Approximately 1 year
|
4.5%
1/22 • Number of events 1 • Approximately 1 year
|
|
Investigations
Neutrophil Count, Decreased
|
85.0%
17/20 • Number of events 76 • Approximately 1 year
|
72.7%
16/22 • Number of events 79 • Approximately 1 year
|
|
Investigations
Platelet Count Decreased
|
30.0%
6/20 • Number of events 23 • Approximately 1 year
|
4.5%
1/22 • Number of events 6 • Approximately 1 year
|
|
Investigations
White Blood Cell Count Decreased
|
55.0%
11/20 • Number of events 43 • Approximately 1 year
|
22.7%
5/22 • Number of events 27 • Approximately 1 year
|
|
Gastrointestinal disorders
Diarrhea
|
55.0%
11/20 • Number of events 35 • Approximately 1 year
|
72.7%
16/22 • Number of events 30 • Approximately 1 year
|
|
Nervous system disorders
Dizziness
|
25.0%
5/20 • Number of events 5 • Approximately 1 year
|
22.7%
5/22 • Number of events 8 • Approximately 1 year
|
|
Eye disorders
Dry Eyes
|
10.0%
2/20 • Number of events 2 • Approximately 1 year
|
4.5%
1/22 • Number of events 1 • Approximately 1 year
|
|
Nervous system disorders
Dysgeusia
|
5.0%
1/20 • Number of events 1 • Approximately 1 year
|
9.1%
2/22 • Number of events 2 • Approximately 1 year
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
10.0%
2/20 • Number of events 3 • Approximately 1 year
|
13.6%
3/22 • Number of events 3 • Approximately 1 year
|
|
Renal and urinary disorders
Dysuria
|
5.0%
1/20 • Number of events 1 • Approximately 1 year
|
9.1%
2/22 • Number of events 2 • Approximately 1 year
|
|
General disorders
Edema
|
20.0%
4/20 • Number of events 4 • Approximately 1 year
|
4.5%
1/22 • Number of events 1 • Approximately 1 year
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
35.0%
7/20 • Number of events 7 • Approximately 1 year
|
22.7%
5/22 • Number of events 5 • Approximately 1 year
|
|
General disorders
Numbness
|
10.0%
2/20 • Number of events 3 • Approximately 1 year
|
0.00%
0/22 • Approximately 1 year
|
|
General disorders
Fall
|
5.0%
1/20 • Number of events 1 • Approximately 1 year
|
9.1%
2/22 • Number of events 2 • Approximately 1 year
|
|
General disorders
Fatigue
|
65.0%
13/20 • Number of events 20 • Approximately 1 year
|
63.6%
14/22 • Number of events 21 • Approximately 1 year
|
|
General disorders
fever
|
20.0%
4/20 • Number of events 8 • Approximately 1 year
|
13.6%
3/22 • Number of events 3 • Approximately 1 year
|
|
General disorders
Flu like symptoms
|
15.0%
3/20 • Number of events 3 • Approximately 1 year
|
9.1%
2/22 • Number of events 2 • Approximately 1 year
|
|
Nervous system disorders
Headache
|
35.0%
7/20 • Number of events 10 • Approximately 1 year
|
27.3%
6/22 • Number of events 7 • Approximately 1 year
|
|
General disorders
Hoarseness
|
10.0%
2/20 • Number of events 2 • Approximately 1 year
|
4.5%
1/22 • Number of events 1 • Approximately 1 year
|
|
General disorders
Hot Flashes
|
10.0%
2/20 • Number of events 2 • Approximately 1 year
|
18.2%
4/22 • Number of events 4 • Approximately 1 year
|
|
Metabolism and nutrition disorders
Hyperglycemia
|
5.0%
1/20 • Number of events 2 • Approximately 1 year
|
4.5%
1/22 • Number of events 1 • Approximately 1 year
|
|
Metabolism and nutrition disorders
Hyperkalemia
|
10.0%
2/20 • Number of events 9 • Approximately 1 year
|
0.00%
0/22 • Approximately 1 year
|
|
Metabolism and nutrition disorders
Hypoalbuminemia
|
15.0%
3/20 • Number of events 8 • Approximately 1 year
|
9.1%
2/22 • Number of events 2 • Approximately 1 year
|
|
Metabolism and nutrition disorders
Hypocalcemia
|
10.0%
2/20 • Number of events 10 • Approximately 1 year
|
13.6%
3/22 • Number of events 3 • Approximately 1 year
|
|
Metabolism and nutrition disorders
Hypokalemia
|
30.0%
6/20 • Number of events 10 • Approximately 1 year
|
9.1%
2/22 • Number of events 2 • Approximately 1 year
|
|
Metabolism and nutrition disorders
Hyponatremia
|
5.0%
1/20 • Number of events 7 • Approximately 1 year
|
4.5%
1/22 • Number of events 1 • Approximately 1 year
|
|
Metabolism and nutrition disorders
hypophosphatemia
|
5.0%
1/20 • Number of events 3 • Approximately 1 year
|
0.00%
0/22 • Approximately 1 year
|
|
Infections and infestations
Infection
|
60.0%
12/20 • Number of events 19 • Approximately 1 year
|
27.3%
6/22 • Number of events 7 • Approximately 1 year
|
|
Blood and lymphatic system disorders
Increased INR
|
10.0%
2/20 • Number of events 2 • Approximately 1 year
|
0.00%
0/22 • Approximately 1 year
|
|
Psychiatric disorders
Insomnia
|
15.0%
3/20 • Number of events 4 • Approximately 1 year
|
9.1%
2/22 • Number of events 2 • Approximately 1 year
|
|
Investigations
Lymphocyte Count Decreased
|
15.0%
3/20 • Number of events 20 • Approximately 1 year
|
13.6%
3/22 • Number of events 12 • Approximately 1 year
|
|
Skin and subcutaneous tissue disorders
maculopapular rash
|
10.0%
2/20 • Number of events 8 • Approximately 1 year
|
13.6%
3/22 • Number of events 3 • Approximately 1 year
|
|
Nervous system disorders
Memory Impairment
|
5.0%
1/20 • Number of events 1 • Approximately 1 year
|
4.5%
1/22 • Number of events 1 • Approximately 1 year
|
|
Infections and infestations
Mucositis
|
45.0%
9/20 • Number of events 17 • Approximately 1 year
|
9.1%
2/22 • Number of events 2 • Approximately 1 year
|
|
Musculoskeletal and connective tissue disorders
Weakness
|
10.0%
2/20 • Number of events 2 • Approximately 1 year
|
0.00%
0/22 • Approximately 1 year
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
15.0%
3/20 • Number of events 3 • Approximately 1 year
|
9.1%
2/22 • Number of events 2 • Approximately 1 year
|
|
Gastrointestinal disorders
Nausea
|
55.0%
11/20 • Number of events 25 • Approximately 1 year
|
54.5%
12/22 • Number of events 18 • Approximately 1 year
|
|
Nervous system disorders
Neuropathy
|
5.0%
1/20 • Number of events 1 • Approximately 1 year
|
4.5%
1/22 • Number of events 1 • Approximately 1 year
|
|
Skin and subcutaneous tissue disorders
Parethesias
|
10.0%
2/20 • Number of events 2 • Approximately 1 year
|
4.5%
1/22 • Number of events 1 • Approximately 1 year
|
|
Skin and subcutaneous tissue disorders
Pruritis
|
20.0%
4/20 • Number of events 6 • Approximately 1 year
|
4.5%
1/22 • Number of events 1 • Approximately 1 year
|
|
Infections and infestations
Sepsis
|
10.0%
2/20 • Number of events 2 • Approximately 1 year
|
0.00%
0/22 • Approximately 1 year
|
|
Skin and subcutaneous tissue disorders
Skin Laceration
|
5.0%
1/20 • Number of events 2 • Approximately 1 year
|
0.00%
0/22 • Approximately 1 year
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
15.0%
3/20 • Number of events 6 • Approximately 1 year
|
4.5%
1/22 • Number of events 2 • Approximately 1 year
|
|
Renal and urinary disorders
Urinary Retention
|
15.0%
3/20 • Number of events 3 • Approximately 1 year
|
0.00%
0/22 • Approximately 1 year
|
|
Reproductive system and breast disorders
Vaginal dryness
|
10.0%
2/20 • Number of events 3 • Approximately 1 year
|
0.00%
0/22 • Approximately 1 year
|
|
Gastrointestinal disorders
Vomiting
|
50.0%
10/20 • Number of events 20 • Approximately 1 year
|
27.3%
6/22 • Number of events 11 • Approximately 1 year
|
|
General disorders
Weight Loss
|
25.0%
5/20 • Number of events 6 • Approximately 1 year
|
9.1%
2/22 • Number of events 2 • Approximately 1 year
|
|
Respiratory, thoracic and mediastinal disorders
Sore Throat
|
5.0%
1/20 • Number of events 1 • Approximately 1 year
|
9.1%
2/22 • Number of events 3 • Approximately 1 year
|
|
Gastrointestinal disorders
Gastroesophageal reflux disease
|
0.00%
0/20 • Approximately 1 year
|
13.6%
3/22 • Number of events 4 • Approximately 1 year
|
|
Psychiatric disorders
Depression
|
0.00%
0/20 • Approximately 1 year
|
13.6%
3/22 • Number of events 3 • Approximately 1 year
|
|
Gastrointestinal disorders
Dyspepsia/Dysphagia
|
0.00%
0/20 • Approximately 1 year
|
9.1%
2/22 • Number of events 3 • Approximately 1 year
|
|
Investigations
Creatinine, Elevated
|
0.00%
0/20 • Approximately 1 year
|
9.1%
2/22 • Number of events 3 • Approximately 1 year
|
Additional Information
Elena Shagisultanova, MD, PhD
University of Colorado Hospital
Phone: 7208480300
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place