Trial Outcomes & Findings for Fulvestrant, Palbociclib and Erdafitinib in ER+/HER2-/FGFR-amplified Metastatic Breast Cancer (NCT NCT03238196)

NCT ID: NCT03238196

Last Updated: 2024-11-14

Results Overview

Number of participants with DLT in the first cycle for the determination of the MTD.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

35 participants

Primary outcome timeframe

From the time of randomization up to 4 weeks of treatment (cycle 1), for each patient

Results posted on

2024-11-14

Participant Flow

Participants were recruited to this trial from August 2017 to January 2021 at five medical centers.

Participant milestones

Participant milestones
Measure	Expansion Fulvestrant - injection into muscle 1 time per month Palbociclib capsule taken by mouth 1 time per day every 21 days followed by 1 week of rest (no drug taken) Erdafitinib tablet taken by mouth 1 time per day Erdafitinib: 6 mg Palbociclib: 125 mg Fulvestrant: 500 mg	Fulvestrant 500mg/Palbociclib 125mg/Erdafitinib 5mg (Escalation) Participants who were treated with Fulvestrant 500mg, Palbociclib 125mg and Erdafitinib 5mg.	Fulvestrant 500mg/Palbociclib 125mg/Erdafitinib 6mg (Escalation) Participants who were treated with Fulvestrant 500mg, Palbociclib 125mg and Erdafitinib 6mg.	Fulvestrant 500mg, Palbociclib 125mg and Erdafitinib 8mg (Escalation) Participants who were treated with Fulvestrant 500mg, Palbociclib 125mg and Erdafitinib 8mg.
Overall Study STARTED	22	3	6	4
Overall Study COMPLETED	0	0	0	0
Overall Study NOT COMPLETED	22	3	6	4

Reasons for withdrawal

Reasons for withdrawal
Measure	Expansion Fulvestrant - injection into muscle 1 time per month Palbociclib capsule taken by mouth 1 time per day every 21 days followed by 1 week of rest (no drug taken) Erdafitinib tablet taken by mouth 1 time per day Erdafitinib: 6 mg Palbociclib: 125 mg Fulvestrant: 500 mg	Fulvestrant 500mg/Palbociclib 125mg/Erdafitinib 5mg (Escalation) Participants who were treated with Fulvestrant 500mg, Palbociclib 125mg and Erdafitinib 5mg.	Fulvestrant 500mg/Palbociclib 125mg/Erdafitinib 6mg (Escalation) Participants who were treated with Fulvestrant 500mg, Palbociclib 125mg and Erdafitinib 6mg.	Fulvestrant 500mg, Palbociclib 125mg and Erdafitinib 8mg (Escalation) Participants who were treated with Fulvestrant 500mg, Palbociclib 125mg and Erdafitinib 8mg.
Overall Study Adverse Event	3	0	2	2
Overall Study Withdrawal by Subject	4	1	1	0
Overall Study Disease progression	14	2	3	2
Overall Study Still on treatment	1	0	0	0

Baseline Characteristics

Fulvestrant, Palbociclib and Erdafitinib in ER+/HER2-/FGFR-amplified Metastatic Breast Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Expansion n=22 Participants Fulvestrant - injection into muscle 1 time per month Palbociclib capsule taken by mouth 1 time per day every 21 days followed by 1 week of rest (no drug taken) Erdafitinib tablet taken by mouth 1 time per day Erdafitinib: 6mg Palbociclib: 125 mg Fulvestrant: 500 mg	Fulvestrant 500mg/Palbociclib 125mg/Erdafitinib 5mg (Escalation) n=3 Participants Participants who were treated with Fulvestrant 500mg, Palbociclib 125mg and Erdafitinib 5mg.	Fulvestrant 500mg/Palbociclib 125mg/Erdafitinib 6mg (Escalation) n=6 Participants Participants who were treated with Fulvestrant 500mg, Palbociclib 125mg and Erdafitinib 6mg.	Fulvestrant 500mg, Palbociclib 125mg and Erdafitinib 8mg (Escalation) n=4 Participants Participants who were treated with Fulvestrant 500mg, Palbociclib 125mg and Erdafitinib 8mg.	Total n=35 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	0 Participants n=4 Participants	0 Participants n=21 Participants
Age, Categorical Between 18 and 65 years	18 Participants n=5 Participants	2 Participants n=7 Participants	5 Participants n=5 Participants	3 Participants n=4 Participants	28 Participants n=21 Participants
Age, Categorical >=65 years	4 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants	1 Participants n=4 Participants	7 Participants n=21 Participants
Sex: Female, Male Female	22 Participants n=5 Participants	3 Participants n=7 Participants	6 Participants n=5 Participants	4 Participants n=4 Participants	35 Participants n=21 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	1 Participants n=21 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	14 Participants n=5 Participants	3 Participants n=7 Participants	3 Participants n=5 Participants	1 Participants n=4 Participants	21 Participants n=21 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	7 Participants n=5 Participants	0 Participants n=7 Participants	3 Participants n=5 Participants	3 Participants n=4 Participants	13 Participants n=21 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Asian	2 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	0 Participants n=4 Participants	3 Participants n=21 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	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	2 Participants n=21 Participants
Race (NIH/OMB) White	17 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants	2 Participants n=4 Participants	24 Participants n=21 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Unknown or Not Reported	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants	2 Participants n=4 Participants	6 Participants n=21 Participants
Region of Enrollment United States	22 participants n=5 Participants	3 participants n=7 Participants	6 participants n=5 Participants	4 participants n=4 Participants	35 participants n=21 Participants

PRIMARY outcome

Timeframe: From the time of randomization up to 4 weeks of treatment (cycle 1), for each patient

Population: Participants who were treated with Fulvestrant 500mg, Palbociclib 125mg and Erdafitinib in Escalation phase.

Number of participants with DLT in the first cycle for the determination of the MTD.

Outcome measures

Outcome measures
Measure	Fulvestrant 500mg/Palbociclib 125mg/Erdafitinib 5mg (Escalation) n=3 Participants Participants take Erdafitinib 5mg orally once a day in 28-day cycle, with Fulvestrant 500mg IM once every 28 days (for cycle 1 it is administered at day 15) and Palbociclib 125mg daily for 21 days out of a 28-day cycle.	Fulvestrant 500mg/Palbociclib 125mg/Erdafitinib 6mg (Escalation) n=6 Participants Participants take Erdafitinib 6mg orally once a day in 28-day cycle, with Fulvestrant 500mg IM once every 28 days (for cycle 1 it is administered at day 15) and Palbociclib 125mg daily for 21 days out of a 28-day cycle.	Fulvestrant 500mg, Palbociclib 125mg and Erdafitinib 8mg (Escalation) n=4 Participants Participants take Erdafitinib 8mg orally once a day in 28-day cycle, with Fulvestrant 500mg IM once every 28 days (for cycle 1 it is administered at day 15) and Palbociclib 125mg daily for 21 days out of a 28-day cycle.
Number of Participants With Dose Limiting Toxicities (DLT) in the First Cycle for the Determination of the Maximum Tolerated Dose (MTD)	0 participants	0 participants	2 participants

SECONDARY outcome

Timeframe: Imaging studies will be performed every 8 weeks from date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 48 months

Population: All participants. This study was a single-arm dose escalation/dose expansion study. Therefore we did not subdivide the dose level groups for the secondary outcomes as the study was not powered for any intra-arm comparisons of clinical benefit.

Assessment of clinical impact \[anti-tumor effect\] of the combination of erdafitinib, palbociclib and fulvestrant in patients with ER+/ FGFR amplified metastatic breast cancer will be assessed by measuring the interval (in months) between treatment initiation and disease progression. Progression-free survival (PFS) time is defined as the time from treatment initiation to progression date or death (whichever comes first). Those alive without prpgression is censored at the last date of known alive. Median PFS time and 95% confidence intervals are obtained using Kaplan-meier method.

Outcome measures

Outcome measures
Measure	Fulvestrant 500mg/Palbociclib 125mg/Erdafitinib 5mg (Escalation) n=35 Participants Participants take Erdafitinib 5mg orally once a day in 28-day cycle, with Fulvestrant 500mg IM once every 28 days (for cycle 1 it is administered at day 15) and Palbociclib 125mg daily for 21 days out of a 28-day cycle.	Fulvestrant 500mg/Palbociclib 125mg/Erdafitinib 6mg (Escalation) Participants take Erdafitinib 6mg orally once a day in 28-day cycle, with Fulvestrant 500mg IM once every 28 days (for cycle 1 it is administered at day 15) and Palbociclib 125mg daily for 21 days out of a 28-day cycle.	Fulvestrant 500mg, Palbociclib 125mg and Erdafitinib 8mg (Escalation) Participants take Erdafitinib 8mg orally once a day in 28-day cycle, with Fulvestrant 500mg IM once every 28 days (for cycle 1 it is administered at day 15) and Palbociclib 125mg daily for 21 days out of a 28-day cycle.
Progression-free Survival	12.4 weeks Interval 8.1 to 22.0	—	—

SECONDARY outcome

Population: Patients received the treatment and had valuable response data. This study was a single-arm dose escalation/dose expansion study. Therefore we did not subdivide the dose level groups for the secondary outcomes as the study was not powered for any intra-arm comparisons of clinical benefit.

Assessment of clinical impact \[anti-tumor effect\] of the combination of erdafitinib, palbociclib and fulvestrant in patients with ER+/ FGFR amplified metastatic breast cancer by measure the rate (%) of complete and partial responses seen in patients with measurable disease. The response of a patient will be evaluated using Solid Tumor Response Criteria RECIST v1.1.

Outcome measures

Outcome measures
Measure	Fulvestrant 500mg/Palbociclib 125mg/Erdafitinib 5mg (Escalation) n=31 Participants Participants take Erdafitinib 5mg orally once a day in 28-day cycle, with Fulvestrant 500mg IM once every 28 days (for cycle 1 it is administered at day 15) and Palbociclib 125mg daily for 21 days out of a 28-day cycle.	Fulvestrant 500mg/Palbociclib 125mg/Erdafitinib 6mg (Escalation) Participants take Erdafitinib 6mg orally once a day in 28-day cycle, with Fulvestrant 500mg IM once every 28 days (for cycle 1 it is administered at day 15) and Palbociclib 125mg daily for 21 days out of a 28-day cycle.	Fulvestrant 500mg, Palbociclib 125mg and Erdafitinib 8mg (Escalation) Participants take Erdafitinib 8mg orally once a day in 28-day cycle, with Fulvestrant 500mg IM once every 28 days (for cycle 1 it is administered at day 15) and Palbociclib 125mg daily for 21 days out of a 28-day cycle.
Overall Response Rate	9.7 percentage of participants Interval 3.3 to 24.9	—	—

SECONDARY outcome

Timeframe: From the time of randomization up to 6 months for each patient

Population: Participants received the treatment and had evaluable response data. This study was a single-arm dose escalation/dose expansion study. Therefore we did not subdivide the dose level groups for the secondary outcomes as the study was not powered for any intra-arm comparisons of clinical benefit.

Assessment of clinical impact \[anti-tumor effect\] of the combination of erdafitinib, palbociclib and fulvestrant in patients with ER+/ FGFR amplified metastatic breast cancer by measure the rate (%) of complete and partial responses + stability of disease at 6 months seen in patients with measurable disease. Response of a patient was evaluated using Solid Tumor Response Criteria -RECIST v1.1.

Outcome measures

Outcome measures
Measure	Fulvestrant 500mg/Palbociclib 125mg/Erdafitinib 5mg (Escalation) n=31 Participants Participants take Erdafitinib 5mg orally once a day in 28-day cycle, with Fulvestrant 500mg IM once every 28 days (for cycle 1 it is administered at day 15) and Palbociclib 125mg daily for 21 days out of a 28-day cycle.	Fulvestrant 500mg/Palbociclib 125mg/Erdafitinib 6mg (Escalation) Participants take Erdafitinib 6mg orally once a day in 28-day cycle, with Fulvestrant 500mg IM once every 28 days (for cycle 1 it is administered at day 15) and Palbociclib 125mg daily for 21 days out of a 28-day cycle.	Fulvestrant 500mg, Palbociclib 125mg and Erdafitinib 8mg (Escalation) Participants take Erdafitinib 8mg orally once a day in 28-day cycle, with Fulvestrant 500mg IM once every 28 days (for cycle 1 it is administered at day 15) and Palbociclib 125mg daily for 21 days out of a 28-day cycle.
Clinical Benefit Rate (CBR; Complete Response + Partial Response + Stable Disease Without Disease Progression at 6 Months)	64.5 percentage of participants Interval 46.9 to 78.9	—	—

SECONDARY outcome

Timeframe: From the time of randomization up to 4 weeks of treatment for each patient

Population: Patients who actually received erdafitinib 5m, 6 mg and 8mg and participated the PK study by measuring the blood plasma concentration. One patients could have PK data at different cycles and days. For dose 5mg, 7 patients had 14 PK data. For daose 6mg, 6 patients had 11 PK data. For dose8mg, 4 patients had 8 PK data.

The area under the plasma concentration-time curve from time zero to the last measurable concentration

Outcome measures

Outcome measures
Measure	Fulvestrant 500mg/Palbociclib 125mg/Erdafitinib 5mg (Escalation) n=7 Participants Participants take Erdafitinib 5mg orally once a day in 28-day cycle, with Fulvestrant 500mg IM once every 28 days (for cycle 1 it is administered at day 15) and Palbociclib 125mg daily for 21 days out of a 28-day cycle.	Fulvestrant 500mg/Palbociclib 125mg/Erdafitinib 6mg (Escalation) n=6 Participants Participants take Erdafitinib 6mg orally once a day in 28-day cycle, with Fulvestrant 500mg IM once every 28 days (for cycle 1 it is administered at day 15) and Palbociclib 125mg daily for 21 days out of a 28-day cycle.	Fulvestrant 500mg, Palbociclib 125mg and Erdafitinib 8mg (Escalation) n=4 Participants Participants take Erdafitinib 8mg orally once a day in 28-day cycle, with Fulvestrant 500mg IM once every 28 days (for cycle 1 it is administered at day 15) and Palbociclib 125mg daily for 21 days out of a 28-day cycle.
Pharmacokinetic Assessment of Erdafitinib - Area Under the Curve (AUC)	1128 ng/ml.hr Standard Deviation 608	718 ng/ml.hr Standard Deviation 521	1268 ng/ml.hr Standard Deviation 827

SECONDARY outcome

Timeframe: From the time of randomization up to 4 weeks of treatment for each patient

The maximum (peak) observed plasma drug concentration after oral dose administration

Outcome measures

Outcome measures
Measure	Fulvestrant 500mg/Palbociclib 125mg/Erdafitinib 5mg (Escalation) n=7 Participants Participants take Erdafitinib 5mg orally once a day in 28-day cycle, with Fulvestrant 500mg IM once every 28 days (for cycle 1 it is administered at day 15) and Palbociclib 125mg daily for 21 days out of a 28-day cycle.	Fulvestrant 500mg/Palbociclib 125mg/Erdafitinib 6mg (Escalation) n=6 Participants Participants take Erdafitinib 6mg orally once a day in 28-day cycle, with Fulvestrant 500mg IM once every 28 days (for cycle 1 it is administered at day 15) and Palbociclib 125mg daily for 21 days out of a 28-day cycle.	Fulvestrant 500mg, Palbociclib 125mg and Erdafitinib 8mg (Escalation) n=8 Participants Participants take Erdafitinib 8mg orally once a day in 28-day cycle, with Fulvestrant 500mg IM once every 28 days (for cycle 1 it is administered at day 15) and Palbociclib 125mg daily for 21 days out of a 28-day cycle.
Pharmacokinetic Assessment of Erdafitinib - Cmax (Maximum Plasma Concentration)	875 ng/ml Standard Deviation 625	668 ng/ml Standard Deviation 528	737 ng/ml Standard Deviation 348

SECONDARY outcome

Timeframe: From the time of randomization up to 4 weeks of treatment for each patient

Time to reach maximum (Cmax) plasma drug concentration after oral dose administration (time)

Outcome measures

Outcome measures
Measure	Fulvestrant 500mg/Palbociclib 125mg/Erdafitinib 5mg (Escalation) n=7 Participants Participants take Erdafitinib 5mg orally once a day in 28-day cycle, with Fulvestrant 500mg IM once every 28 days (for cycle 1 it is administered at day 15) and Palbociclib 125mg daily for 21 days out of a 28-day cycle.	Fulvestrant 500mg/Palbociclib 125mg/Erdafitinib 6mg (Escalation) n=6 Participants Participants take Erdafitinib 6mg orally once a day in 28-day cycle, with Fulvestrant 500mg IM once every 28 days (for cycle 1 it is administered at day 15) and Palbociclib 125mg daily for 21 days out of a 28-day cycle.	Fulvestrant 500mg, Palbociclib 125mg and Erdafitinib 8mg (Escalation) n=4 Participants Participants take Erdafitinib 8mg orally once a day in 28-day cycle, with Fulvestrant 500mg IM once every 28 days (for cycle 1 it is administered at day 15) and Palbociclib 125mg daily for 21 days out of a 28-day cycle.
Pharmacokinetic Assessment of Erdafitinib - Tmax	2.8 hour Standard Deviation 2.5	2.5 hour Standard Deviation 1.8	2.8 hour Standard Deviation 2.5

SECONDARY outcome

Timeframe: From the time of randomization up to 4 weeks of treatment for each patient

Apparent total body clearance of drug from the plasma after oral administration

Outcome measures

Outcome measures
Measure	Fulvestrant 500mg/Palbociclib 125mg/Erdafitinib 5mg (Escalation) n=7 Participants Participants take Erdafitinib 5mg orally once a day in 28-day cycle, with Fulvestrant 500mg IM once every 28 days (for cycle 1 it is administered at day 15) and Palbociclib 125mg daily for 21 days out of a 28-day cycle.	Fulvestrant 500mg/Palbociclib 125mg/Erdafitinib 6mg (Escalation) n=6 Participants Participants take Erdafitinib 6mg orally once a day in 28-day cycle, with Fulvestrant 500mg IM once every 28 days (for cycle 1 it is administered at day 15) and Palbociclib 125mg daily for 21 days out of a 28-day cycle.	Fulvestrant 500mg, Palbociclib 125mg and Erdafitinib 8mg (Escalation) n=4 Participants Participants take Erdafitinib 8mg orally once a day in 28-day cycle, with Fulvestrant 500mg IM once every 28 days (for cycle 1 it is administered at day 15) and Palbociclib 125mg daily for 21 days out of a 28-day cycle.
Pharmacokinetic Assessment of Erdafitinib - CL/F	5.5 l/hr Standard Deviation 2.6	11.3 l/hr Standard Deviation 5.5	8.6 l/hr Standard Deviation 4.6

SECONDARY outcome

Timeframe: From date of randomization until 28 days post treatment discontinuation from any cause, assessed up to 48 months

Population: All patients treated. This study was a single-arm dose escalation/dose expansion study. Therefore we did not subdivide the dose level groups for the secondary outcomes as the study was not powered for any intra-arm comparisons of clinical benefit.

Assessment of adverse events throughout the study. The number of patients who had any grade of adverse events were reported.

Outcome measures

Outcome measures
Measure	Fulvestrant 500mg/Palbociclib 125mg/Erdafitinib 5mg (Escalation) n=35 Participants Participants take Erdafitinib 5mg orally once a day in 28-day cycle, with Fulvestrant 500mg IM once every 28 days (for cycle 1 it is administered at day 15) and Palbociclib 125mg daily for 21 days out of a 28-day cycle.	Fulvestrant 500mg/Palbociclib 125mg/Erdafitinib 6mg (Escalation) Participants take Erdafitinib 6mg orally once a day in 28-day cycle, with Fulvestrant 500mg IM once every 28 days (for cycle 1 it is administered at day 15) and Palbociclib 125mg daily for 21 days out of a 28-day cycle.	Fulvestrant 500mg, Palbociclib 125mg and Erdafitinib 8mg (Escalation) Participants take Erdafitinib 8mg orally once a day in 28-day cycle, with Fulvestrant 500mg IM once every 28 days (for cycle 1 it is administered at day 15) and Palbociclib 125mg daily for 21 days out of a 28-day cycle.
Incidence of Treatment-Emergent Adverse Events [Tolerability] Oral mucositis, any grade	27 patients	—	—
Incidence of Treatment-Emergent Adverse Events [Tolerability] Hyperphosphatemia, any grade	29 patients	—	—
Incidence of Treatment-Emergent Adverse Events [Tolerability] Palmar-plantar erythrodysesthesia syndrome, any grade	18 patients	—	—
Incidence of Treatment-Emergent Adverse Events [Tolerability] Diarrhea, any grade	14 patients	—	—
Incidence of Treatment-Emergent Adverse Events [Tolerability] Constipation, any grade	19 patients	—	—
Incidence of Treatment-Emergent Adverse Events [Tolerability] Dysgeusia, any grade	19 patients	—	—
Incidence of Treatment-Emergent Adverse Events [Tolerability] Dry mouth, any grade	18 patients	—	—
Incidence of Treatment-Emergent Adverse Events [Tolerability] Nail alterations, any grade	13 patients	—	—
Incidence of Treatment-Emergent Adverse Events [Tolerability] Sore throat, any grade	8 patients	—	—
Incidence of Treatment-Emergent Adverse Events [Tolerability] Alopecia, any grade	13 patients	—	—
Incidence of Treatment-Emergent Adverse Events [Tolerability] Dry skin, any grade	12 patients	—	—
Incidence of Treatment-Emergent Adverse Events [Tolerability] Anorexia, any grade	7 patients	—	—
Incidence of Treatment-Emergent Adverse Events [Tolerability] Epistaxis, any grade	9 patients	—	—
Incidence of Treatment-Emergent Adverse Events [Tolerability] Dry eye, any grade	10 patients	—	—
Incidence of Treatment-Emergent Adverse Events [Tolerability] Skin ulceration, any grade	2 patients	—	—
Incidence of Treatment-Emergent Adverse Events [Tolerability] Vision changes/alterations, any grade	6 patients	—	—
Incidence of Treatment-Emergent Adverse Events [Tolerability] Neutrophil count decreased, grade 4	1 patients	—	—
Incidence of Treatment-Emergent Adverse Events [Tolerability] Palmar-plantar erythrodysesthesia syndrome, grade 3	2 patients	—	—
Incidence of Treatment-Emergent Adverse Events [Tolerability] Abdominal pain, any grade	5 patients	—	—
Incidence of Treatment-Emergent Adverse Events [Tolerability] Dizziness, any grade	3 patients	—	—
Incidence of Treatment-Emergent Adverse Events [Tolerability] Gastroesophageal reflux disease, any grade	5 patients	—	—
Incidence of Treatment-Emergent Adverse Events [Tolerability] Hypotension, any grade	3 patients	—	—
Incidence of Treatment-Emergent Adverse Events [Tolerability] Elevated ALT, any grade	1 patients	—	—
Incidence of Treatment-Emergent Adverse Events [Tolerability] Elevated AST, any grade	3 patients	—	—
Incidence of Treatment-Emergent Adverse Events [Tolerability] Colitis, any grade	1 patients	—	—
Incidence of Treatment-Emergent Adverse Events [Tolerability] Esophagitis, any grade	2 patients	—	—
Incidence of Treatment-Emergent Adverse Events [Tolerability] Eye keratopathy, any grade	1 patients	—	—
Incidence of Treatment-Emergent Adverse Events [Tolerability] Hyperkeratosis, any grade	1 patients	—	—
Incidence of Treatment-Emergent Adverse Events [Tolerability] Syncope, any grade	1 patients	—	—
Incidence of Treatment-Emergent Adverse Events [Tolerability] Neutropenia, any grade	25 patients	—	—
Incidence of Treatment-Emergent Adverse Events [Tolerability] Leucopenia, any grade	15 patients	—	—
Incidence of Treatment-Emergent Adverse Events [Tolerability] Anemia, any grade	12 patients	—	—
Incidence of Treatment-Emergent Adverse Events [Tolerability] Thrombocytopenia, any grade	2 patients	—	—
Incidence of Treatment-Emergent Adverse Events [Tolerability] Lymphopenia, any grade	1 patients	—	—
Incidence of Treatment-Emergent Adverse Events [Tolerability] Febrile neutropenia, any grade	1 patients	—	—
Incidence of Treatment-Emergent Adverse Events [Tolerability] Neutrophilia, any grade	1 patients	—	—
Incidence of Treatment-Emergent Adverse Events [Tolerability] Thromboembolic event, any grade	1 patients	—	—
Incidence of Treatment-Emergent Adverse Events [Tolerability] Fatigue, any grade	15 patients	—	—
Incidence of Treatment-Emergent Adverse Events [Tolerability] Nausea, any grade	6 patients	—	—
Incidence of Treatment-Emergent Adverse Events [Tolerability] Vomiting, any grade	6 patients	—	—

OTHER_PRE_SPECIFIED outcome

Timeframe: During the first 8 weeks of treatment (days 1, 8, 15, 22 of cycle 1 and days 1 and 15 of cycle 2)

Other events: 22 other events

Deaths: 3 deaths

Fulvestrant 500mg/Palbociclib 125mg/Erdafitinib 6mg

Serious events: 1 serious events

Other events: 6 other events

Deaths: 6 deaths

Fulvestrant 500mg, Palbociclib 125mg and Erdafitinib 8mg

Serious events: 1 serious events

Other events: 4 other events

Deaths: 2 deaths

Serious adverse events

Serious adverse events
Measure	Fulvestrant 500mg/Palbociclib 125mg/Erdafitinib 5mg n=3 participants at risk Participants who were treated with Fulvestrant 500mg, Palbociclib 125mg and Erdafitinib 5mg.	Expansion n=22 participants at risk Fulvestrant - injection into muscle 1 time per month Palbociclib capsule taken by mouth 1 time per day every 21 days followed by 1 week of rest (no drug taken) Erdafitinib tablet taken by mouth 1 time per day Erdafitinib: 6mg Palbociclib: 125 mg Fulvestrant: 500 mg	Fulvestrant 500mg/Palbociclib 125mg/Erdafitinib 6mg n=6 participants at risk Participants who were treated with Fulvestrant 500mg, Palbociclib 125mg and Erdafitinib 6mg.	Fulvestrant 500mg, Palbociclib 125mg and Erdafitinib 8mg n=4 participants at risk Participants who were treated with Fulvestrant 500mg, Palbociclib 125mg and Erdafitinib 8mg.
Infections and infestations Sepsis	33.3% 1/3 • Number of events 1 • Time frame for Serious adverse events and Other (Not Including Serious) Adverse Events: From time of informed consent signature to within 30 days of the last documented dose of study medication up to approximately 36 months.	0.00% 0/22 • Time frame for Serious adverse events and Other (Not Including Serious) Adverse Events: From time of informed consent signature to within 30 days of the last documented dose of study medication up to approximately 36 months.	0.00% 0/6 • Time frame for Serious adverse events and Other (Not Including Serious) Adverse Events: From time of informed consent signature to within 30 days of the last documented dose of study medication up to approximately 36 months.	0.00% 0/4 • Time frame for Serious adverse events and Other (Not Including Serious) Adverse Events: From time of informed consent signature to within 30 days of the last documented dose of study medication up to approximately 36 months.
Vascular disorders Pulmonary embolism	0.00% 0/3 • Time frame for Serious adverse events and Other (Not Including Serious) Adverse Events: From time of informed consent signature to within 30 days of the last documented dose of study medication up to approximately 36 months.	4.5% 1/22 • Number of events 1 • Time frame for Serious adverse events and Other (Not Including Serious) Adverse Events: From time of informed consent signature to within 30 days of the last documented dose of study medication up to approximately 36 months.	16.7% 1/6 • Number of events 1 • Time frame for Serious adverse events and Other (Not Including Serious) Adverse Events: From time of informed consent signature to within 30 days of the last documented dose of study medication up to approximately 36 months.	0.00% 0/4 • Time frame for Serious adverse events and Other (Not Including Serious) Adverse Events: From time of informed consent signature to within 30 days of the last documented dose of study medication up to approximately 36 months.
Blood and lymphatic system disorders Febrile neutropenia	33.3% 1/3 • Number of events 1 • Time frame for Serious adverse events and Other (Not Including Serious) Adverse Events: From time of informed consent signature to within 30 days of the last documented dose of study medication up to approximately 36 months.	0.00% 0/22 • Time frame for Serious adverse events and Other (Not Including Serious) Adverse Events: From time of informed consent signature to within 30 days of the last documented dose of study medication up to approximately 36 months.	0.00% 0/6 • Time frame for Serious adverse events and Other (Not Including Serious) Adverse Events: From time of informed consent signature to within 30 days of the last documented dose of study medication up to approximately 36 months.	0.00% 0/4 • Time frame for Serious adverse events and Other (Not Including Serious) Adverse Events: From time of informed consent signature to within 30 days of the last documented dose of study medication up to approximately 36 months.
Musculoskeletal and connective tissue disorders Muscle weakness	0.00% 0/3 • Time frame for Serious adverse events and Other (Not Including Serious) Adverse Events: From time of informed consent signature to within 30 days of the last documented dose of study medication up to approximately 36 months.	4.5% 1/22 • Number of events 1 • Time frame for Serious adverse events and Other (Not Including Serious) Adverse Events: From time of informed consent signature to within 30 days of the last documented dose of study medication up to approximately 36 months.	16.7% 1/6 • Number of events 1 • Time frame for Serious adverse events and Other (Not Including Serious) Adverse Events: From time of informed consent signature to within 30 days of the last documented dose of study medication up to approximately 36 months.	0.00% 0/4 • Time frame for Serious adverse events and Other (Not Including Serious) Adverse Events: From time of informed consent signature to within 30 days of the last documented dose of study medication up to approximately 36 months.
Investigations Alanine aminotransferase increased	0.00% 0/3 • Time frame for Serious adverse events and Other (Not Including Serious) Adverse Events: From time of informed consent signature to within 30 days of the last documented dose of study medication up to approximately 36 months.	4.5% 1/22 • Number of events 1 • Time frame for Serious adverse events and Other (Not Including Serious) Adverse Events: From time of informed consent signature to within 30 days of the last documented dose of study medication up to approximately 36 months.	0.00% 0/6 • Time frame for Serious adverse events and Other (Not Including Serious) Adverse Events: From time of informed consent signature to within 30 days of the last documented dose of study medication up to approximately 36 months.	25.0% 1/4 • Number of events 1 • Time frame for Serious adverse events and Other (Not Including Serious) Adverse Events: From time of informed consent signature to within 30 days of the last documented dose of study medication up to approximately 36 months.
Investigations Aspartate aminotransferase increased	0.00% 0/3 • Time frame for Serious adverse events and Other (Not Including Serious) Adverse Events: From time of informed consent signature to within 30 days of the last documented dose of study medication up to approximately 36 months.	4.5% 1/22 • Number of events 1 • Time frame for Serious adverse events and Other (Not Including Serious) Adverse Events: From time of informed consent signature to within 30 days of the last documented dose of study medication up to approximately 36 months.	0.00% 0/6 • Time frame for Serious adverse events and Other (Not Including Serious) Adverse Events: From time of informed consent signature to within 30 days of the last documented dose of study medication up to approximately 36 months.	25.0% 1/4 • Number of events 1 • Time frame for Serious adverse events and Other (Not Including Serious) Adverse Events: From time of informed consent signature to within 30 days of the last documented dose of study medication up to approximately 36 months.
General disorders Fatigue	0.00% 0/3 • Time frame for Serious adverse events and Other (Not Including Serious) Adverse Events: From time of informed consent signature to within 30 days of the last documented dose of study medication up to approximately 36 months.	4.5% 1/22 • Number of events 2 • Time frame for Serious adverse events and Other (Not Including Serious) Adverse Events: From time of informed consent signature to within 30 days of the last documented dose of study medication up to approximately 36 months.	0.00% 0/6 • Time frame for Serious adverse events and Other (Not Including Serious) Adverse Events: From time of informed consent signature to within 30 days of the last documented dose of study medication up to approximately 36 months.	0.00% 0/4 • Time frame for Serious adverse events and Other (Not Including Serious) Adverse Events: From time of informed consent signature to within 30 days of the last documented dose of study medication up to approximately 36 months.
Investigations Blood bilirubin increased	0.00% 0/3 • Time frame for Serious adverse events and Other (Not Including Serious) Adverse Events: From time of informed consent signature to within 30 days of the last documented dose of study medication up to approximately 36 months.	4.5% 1/22 • Number of events 1 • Time frame for Serious adverse events and Other (Not Including Serious) Adverse Events: From time of informed consent signature to within 30 days of the last documented dose of study medication up to approximately 36 months.	0.00% 0/6 • Time frame for Serious adverse events and Other (Not Including Serious) Adverse Events: From time of informed consent signature to within 30 days of the last documented dose of study medication up to approximately 36 months.	0.00% 0/4 • Time frame for Serious adverse events and Other (Not Including Serious) Adverse Events: From time of informed consent signature to within 30 days of the last documented dose of study medication up to approximately 36 months.
Gastrointestinal disorders Colitis	0.00% 0/3 • Time frame for Serious adverse events and Other (Not Including Serious) Adverse Events: From time of informed consent signature to within 30 days of the last documented dose of study medication up to approximately 36 months.	4.5% 1/22 • Number of events 1 • Time frame for Serious adverse events and Other (Not Including Serious) Adverse Events: From time of informed consent signature to within 30 days of the last documented dose of study medication up to approximately 36 months.	0.00% 0/6 • Time frame for Serious adverse events and Other (Not Including Serious) Adverse Events: From time of informed consent signature to within 30 days of the last documented dose of study medication up to approximately 36 months.	0.00% 0/4 • Time frame for Serious adverse events and Other (Not Including Serious) Adverse Events: From time of informed consent signature to within 30 days of the last documented dose of study medication up to approximately 36 months.
Vascular disorders Hypotension	0.00% 0/3 • Time frame for Serious adverse events and Other (Not Including Serious) Adverse Events: From time of informed consent signature to within 30 days of the last documented dose of study medication up to approximately 36 months.	4.5% 1/22 • Number of events 1 • Time frame for Serious adverse events and Other (Not Including Serious) Adverse Events: From time of informed consent signature to within 30 days of the last documented dose of study medication up to approximately 36 months.	0.00% 0/6 • Time frame for Serious adverse events and Other (Not Including Serious) Adverse Events: From time of informed consent signature to within 30 days of the last documented dose of study medication up to approximately 36 months.	0.00% 0/4 • Time frame for Serious adverse events and Other (Not Including Serious) Adverse Events: From time of informed consent signature to within 30 days of the last documented dose of study medication up to approximately 36 months.
Vascular disorders Deep Vein Thrombosis	0.00% 0/3 • Time frame for Serious adverse events and Other (Not Including Serious) Adverse Events: From time of informed consent signature to within 30 days of the last documented dose of study medication up to approximately 36 months.	4.5% 1/22 • Number of events 1 • Time frame for Serious adverse events and Other (Not Including Serious) Adverse Events: From time of informed consent signature to within 30 days of the last documented dose of study medication up to approximately 36 months.	0.00% 0/6 • Time frame for Serious adverse events and Other (Not Including Serious) Adverse Events: From time of informed consent signature to within 30 days of the last documented dose of study medication up to approximately 36 months.	0.00% 0/4 • Time frame for Serious adverse events and Other (Not Including Serious) Adverse Events: From time of informed consent signature to within 30 days of the last documented dose of study medication up to approximately 36 months.
Infections and infestations Lung infection	0.00% 0/3 • Time frame for Serious adverse events and Other (Not Including Serious) Adverse Events: From time of informed consent signature to within 30 days of the last documented dose of study medication up to approximately 36 months.	4.5% 1/22 • Number of events 2 • Time frame for Serious adverse events and Other (Not Including Serious) Adverse Events: From time of informed consent signature to within 30 days of the last documented dose of study medication up to approximately 36 months.	0.00% 0/6 • Time frame for Serious adverse events and Other (Not Including Serious) Adverse Events: From time of informed consent signature to within 30 days of the last documented dose of study medication up to approximately 36 months.	0.00% 0/4 • Time frame for Serious adverse events and Other (Not Including Serious) Adverse Events: From time of informed consent signature to within 30 days of the last documented dose of study medication up to approximately 36 months.
Eye disorders Dry eye	0.00% 0/3 • Time frame for Serious adverse events and Other (Not Including Serious) Adverse Events: From time of informed consent signature to within 30 days of the last documented dose of study medication up to approximately 36 months.	4.5% 1/22 • Number of events 1 • Time frame for Serious adverse events and Other (Not Including Serious) Adverse Events: From time of informed consent signature to within 30 days of the last documented dose of study medication up to approximately 36 months.	0.00% 0/6 • Time frame for Serious adverse events and Other (Not Including Serious) Adverse Events: From time of informed consent signature to within 30 days of the last documented dose of study medication up to approximately 36 months.	0.00% 0/4 • Time frame for Serious adverse events and Other (Not Including Serious) Adverse Events: From time of informed consent signature to within 30 days of the last documented dose of study medication up to approximately 36 months.

Other adverse events

Additional Information

Brent Rexer, MD, PhD, Assistant Professor

Vanderbilt-Ingram Cancer Center

Phone: 615-322-4967

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place