Trial Outcomes & Findings for Phase 2 Trial of Seribantumab Plus Fulvestrant in Postmenopausal Women With Metastatic Breast Cancer (NCT NCT03241810)

Last Updated: 2020-09-02

Results Overview

Progression Free Survival is defined as the time from randomization to the first documented radiographical progression of disease using RECIST v1.1 or death from any cause, whichever comes first as assessed by the investigator. The tumor assessment (i.e., scan dates) was used for progression/censor date not the date corresponding to the determination of overall response. Progression-free survival time distribution and median survival for each treatment group were analyzed using the Kaplan-Meier method.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

22 participants

Primary outcome timeframe

Randomization until progression of disease or death due to any cause up to 13 months (The study terminated prematurely) . The primary analysis was planned to be initiated when 58 PFS events have occurred

Results posted on

2020-09-02

Participant Flow

At the time of the study termination by the prior Sponsor (Merrimack Pharmaceuticals), 62 sites participated in the study (27 in North America and 35 in Europe).

Participant milestones

Participant milestones
Measure	Arm A (Experimental): Seribantumab and Fulvestrant Seribantumab (a human monoclonal antibody that targets ErbB3, a cell surface receptor that is activated by the ligand heregulin. Heregulin-driven ErbB3 signaling has been implicated as a mechanism of tumor growth and resistance to targeted, cytotoxic and anti-endocrine therapies. When used in the combination setting, seribantumab is designed to block ErbB3 signaling in order to enhance the anti-tumor effect of a combination therapy partner): fixed dose of 3000 mg intravenously (IV) on day 1 and 15 of each 28-day cycle Fulvestrant (a drug treatment of hormone receptor-positive metastatic breast cancer in post-menopausal women with disease progression following anti-estrogen therapy. It is an estrogen receptor antagonist with no agonist effects, which works both by down-regulating and by degrading the estrogen receptor): 500 mg intramuscularly (IM) on Days 1 and 15 of Cycle 1, and then on Day 1 of each subsequent 28 day cycle	Arm B (Control): Placebo and Fulvestrant Placebo: intravenously (IV) on day 1 and 15 of each 28-day cycle Fulvestrant: (a drug treatment of hormone receptor-positive metastatic breast cancer in post-menopausal women with disease progression following anti-estrogen therapy. It is an estrogen receptor antagonist with no agonist effects, which works both by down-regulating and by degrading the estrogen receptor): 500 mg intramuscularly (IM) on Days 1 and 15 of Cycle 1, and then on Day 1 of each subsequent 28 day cycle
Overall Study STARTED	11	11
Overall Study COMPLETED	11	11
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Phase 2 Trial of Seribantumab Plus Fulvestrant in Postmenopausal Women With Metastatic Breast Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Arm A (Experimental): Seribantumab and Fulvestrant n=11 Participants Seribantumab (a human monoclonal antibody that targets ErbB3, a cell surface receptor that is activated by the ligand heregulin. Heregulin-driven ErbB3 signaling has been implicated as a mechanism of tumor growth and resistance to targeted, cytotoxic and anti-endocrine therapies. When used in the combination setting, seribantumab is designed to block ErbB3 signaling in order to enhance the anti-tumor effect of a combination therapy partner): fixed dose of 3000 mg intravenously (IV) on day 1 and 15 of each 28-day cycle Fulvestrant (a drug treatment of hormone receptor-positive metastatic breast cancer in post-menopausal women with disease progression following anti-estrogen therapy. It is an estrogen receptor antagonist with no agonist effects, which works both by down-regulating and by degrading the estrogen receptor): 500 mg intramuscularly (IM) on Days 1 and 15 of Cycle 1, and then on Day 1 of each subsequent 28 day cycle	Arm B (Control): Placebo and Fulvestrant n=11 Participants Placebo: intravenously (IV) on day 1 and 15 of each 28-day cycle Fulvestrant: (a drug treatment of hormone receptor-positive metastatic breast cancer in post-menopausal women with disease progression following anti-estrogen therapy. It is an estrogen receptor antagonist with no agonist effects, which works both by down-regulating and by degrading the estrogen receptor): 500 mg intramuscularly (IM) on Days 1 and 15 of Cycle 1, and then on Day 1 of each subsequent 28 day cycle	Total n=22 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	8 Participants n=5 Participants	7 Participants n=7 Participants	15 Participants n=5 Participants
Age, Categorical >=65 years	3 Participants n=5 Participants	4 Participants n=7 Participants	7 Participants n=5 Participants
Sex: Female, Male Female	11 Participants n=5 Participants	11 Participants n=7 Participants	22 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	0 Participants n=7 Participants	0 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	11 Participants n=7 Participants	22 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 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	1 Participants n=5 Participants	0 Participants n=7 Participants	1 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	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) White	10 Participants n=5 Participants	9 Participants n=7 Participants	19 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	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Region of Enrollment Canada	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Region of Enrollment Belgium	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants
Region of Enrollment United States	5 Participants n=5 Participants	6 Participants n=7 Participants	11 Participants n=5 Participants
Region of Enrollment Spain	4 Participants n=5 Participants	3 Participants n=7 Participants	7 Participants n=5 Participants
Metastatic burden (TNM Stage at Initial Diagnosis) TNM Stage I	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Metastatic burden (TNM Stage at Initial Diagnosis) TNM Stage II	0 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants
Metastatic burden (TNM Stage at Initial Diagnosis) TNM Stage IIa	4 Participants n=5 Participants	0 Participants n=7 Participants	4 Participants n=5 Participants
Metastatic burden (TNM Stage at Initial Diagnosis) TNM Stage IIb	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Metastatic burden (TNM Stage at Initial Diagnosis) TNM Stage III	0 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants
Metastatic burden (TNM Stage at Initial Diagnosis) TNM Stage IIIa	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Metastatic burden (TNM Stage at Initial Diagnosis) TNM Stage IIIc	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Metastatic burden (TNM Stage at Initial Diagnosis) TNM Stage IV	4 Participants n=5 Participants	6 Participants n=7 Participants	10 Participants n=5 Participants
Heregulin positive status and staining in archival tissue	11 Participants n=5 Participants	11 Participants n=7 Participants	22 Participants n=5 Participants

PRIMARY outcome

Timeframe: Randomization until progression of disease or death due to any cause up to 13 months (The study terminated prematurely) . The primary analysis was planned to be initiated when 58 PFS events have occurred

Population: Intent-to-Treat (ITT) population treated up to 150 days

Outcome measures

Outcome measures
Measure	Arm A (Experimental): Seribantumab and Fulvestrant n=11 Participants Seribantumab (a human monoclonal antibody that targets ErbB3, a cell surface receptor that is activated by the ligand heregulin. Heregulin-driven ErbB3 signaling has been implicated as a mechanism of tumor growth and resistance to targeted, cytotoxic and anti-endocrine therapies. When used in the combination setting, seribantumab is designed to block ErbB3 signaling in order to enhance the anti-tumor effect of a combination therapy partner): fixed dose of 3000 mg intravenously (IV) on day 1 and 15 of each 28-day cycle Fulvestrant (a drug treatment of hormone receptor-positive metastatic breast cancer in post-menopausal women with disease progression following anti-estrogen therapy. It is an estrogen receptor antagonist with no agonist effects, which works both by down-regulating and by degrading the estrogen receptor): 500 mg intramuscularly (IM) on Days 1 and 15 of Cycle 1, and then on Day 1 of each subsequent 28 day cycle	Arm B (Control): Placebo and Fulvestrant n=11 Participants Placebo: intravenously (IV) on day 1 and 15 of each 28-day cycle Fulvestrant: (a drug treatment of hormone receptor-positive metastatic breast cancer in post-menopausal women with disease progression following anti-estrogen therapy. It is an estrogen receptor antagonist with no agonist effects, which works both by down-regulating and by degrading the estrogen receptor): 500 mg intramuscularly (IM) on Days 1 and 15 of Cycle 1, and then on Day 1 of each subsequent 28 day cycle
Progression Free Survival	1 Participants	1 Participants

SECONDARY outcome

Timeframe: Randomization until death due to any cause up to 13 months (The study terminated prematurely)

Population: Intent-to-Treat (ITT) population treated up to 150 days

Overall Survival (OS) is defined as the time from the date of randomization to the date of death from any cause. The study was terminated on 30 Nov 2018 . Data represents outcomes up to 150 days of treatment.

Outcome measures

Outcome measures
Measure	Arm A (Experimental): Seribantumab and Fulvestrant n=11 Participants Seribantumab (a human monoclonal antibody that targets ErbB3, a cell surface receptor that is activated by the ligand heregulin. Heregulin-driven ErbB3 signaling has been implicated as a mechanism of tumor growth and resistance to targeted, cytotoxic and anti-endocrine therapies. When used in the combination setting, seribantumab is designed to block ErbB3 signaling in order to enhance the anti-tumor effect of a combination therapy partner): fixed dose of 3000 mg intravenously (IV) on day 1 and 15 of each 28-day cycle Fulvestrant (a drug treatment of hormone receptor-positive metastatic breast cancer in post-menopausal women with disease progression following anti-estrogen therapy. It is an estrogen receptor antagonist with no agonist effects, which works both by down-regulating and by degrading the estrogen receptor): 500 mg intramuscularly (IM) on Days 1 and 15 of Cycle 1, and then on Day 1 of each subsequent 28 day cycle	Arm B (Control): Placebo and Fulvestrant n=11 Participants Placebo: intravenously (IV) on day 1 and 15 of each 28-day cycle Fulvestrant: (a drug treatment of hormone receptor-positive metastatic breast cancer in post-menopausal women with disease progression following anti-estrogen therapy. It is an estrogen receptor antagonist with no agonist effects, which works both by down-regulating and by degrading the estrogen receptor): 500 mg intramuscularly (IM) on Days 1 and 15 of Cycle 1, and then on Day 1 of each subsequent 28 day cycle
Overall Survival	1 participants	1 participants

SECONDARY outcome

Timeframe: Randomization through end of study up to 13 months (The study terminated prematurely)

Population: Incomplete data for all subjects due to length of time on study treatment and frequency of scanning. All patients analysed had progressive disease. Therefore, they did not meet the criteria for ORR and hence could not be evaluated for CR or PR

Objective Response Rate (ORR) is defined as the proportion of patients with a RECIST v1.1 response recorded from randomization until disease progression characterized as either a Complete Response (CR) or Partial Response (PR) relative to the total number of evaluable patients.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Randomization to date of objective tumor progression up to 13 months (The study terminated prematurely)

Population: Intent-to-Treat (ITT) population consisted of all participants randomized to the study.

Time to Progression (TTP) is defined as the time from the date of randomization to the date of objective tumor progression.

Outcome measures

Outcome measures
Measure	Arm A (Experimental): Seribantumab and Fulvestrant n=11 Participants Seribantumab (a human monoclonal antibody that targets ErbB3, a cell surface receptor that is activated by the ligand heregulin. Heregulin-driven ErbB3 signaling has been implicated as a mechanism of tumor growth and resistance to targeted, cytotoxic and anti-endocrine therapies. When used in the combination setting, seribantumab is designed to block ErbB3 signaling in order to enhance the anti-tumor effect of a combination therapy partner): fixed dose of 3000 mg intravenously (IV) on day 1 and 15 of each 28-day cycle Fulvestrant (a drug treatment of hormone receptor-positive metastatic breast cancer in post-menopausal women with disease progression following anti-estrogen therapy. It is an estrogen receptor antagonist with no agonist effects, which works both by down-regulating and by degrading the estrogen receptor): 500 mg intramuscularly (IM) on Days 1 and 15 of Cycle 1, and then on Day 1 of each subsequent 28 day cycle	Arm B (Control): Placebo and Fulvestrant n=11 Participants Placebo: intravenously (IV) on day 1 and 15 of each 28-day cycle Fulvestrant: (a drug treatment of hormone receptor-positive metastatic breast cancer in post-menopausal women with disease progression following anti-estrogen therapy. It is an estrogen receptor antagonist with no agonist effects, which works both by down-regulating and by degrading the estrogen receptor): 500 mg intramuscularly (IM) on Days 1 and 15 of Cycle 1, and then on Day 1 of each subsequent 28 day cycle
Time to Progression	52 days Interval 33.25 to 72.25	48 days Interval 34.5 to 58.5

SECONDARY outcome

Timeframe: TEAEs were collected through the study completion (30 Nov 2018), up to 13 months. Frequency and percent summaries were presented for TEAE defined as adverse events that occur or worsen in severity following the first dose of seribantumab, or fulvestrant

Population: Safety Population: The safety population includes patients receiving at least one dose of study medication. All safety analyses were to be performed on this population.

Treatment-emergent adverse events (TEAEs) are defined as any event that occurred after the first dose of study drug and was not present prior to study drug administration or worsened in severity after study drug administration.

Outcome measures

Outcome measures
Measure	Arm A (Experimental): Seribantumab and Fulvestrant n=11 Participants Seribantumab (a human monoclonal antibody that targets ErbB3, a cell surface receptor that is activated by the ligand heregulin. Heregulin-driven ErbB3 signaling has been implicated as a mechanism of tumor growth and resistance to targeted, cytotoxic and anti-endocrine therapies. When used in the combination setting, seribantumab is designed to block ErbB3 signaling in order to enhance the anti-tumor effect of a combination therapy partner): fixed dose of 3000 mg intravenously (IV) on day 1 and 15 of each 28-day cycle Fulvestrant (a drug treatment of hormone receptor-positive metastatic breast cancer in post-menopausal women with disease progression following anti-estrogen therapy. It is an estrogen receptor antagonist with no agonist effects, which works both by down-regulating and by degrading the estrogen receptor): 500 mg intramuscularly (IM) on Days 1 and 15 of Cycle 1, and then on Day 1 of each subsequent 28 day cycle	Arm B (Control): Placebo and Fulvestrant n=11 Participants Placebo: intravenously (IV) on day 1 and 15 of each 28-day cycle Fulvestrant: (a drug treatment of hormone receptor-positive metastatic breast cancer in post-menopausal women with disease progression following anti-estrogen therapy. It is an estrogen receptor antagonist with no agonist effects, which works both by down-regulating and by degrading the estrogen receptor): 500 mg intramuscularly (IM) on Days 1 and 15 of Cycle 1, and then on Day 1 of each subsequent 28 day cycle
Number of Participants With Treatment-emergent Adverse Events Reported With the Combinations of Seribantumab Plus Fulvestrant Versus Fulvestrant Alone Patients with any TEAE-Related	7 participants	4 participants
Number of Participants With Treatment-emergent Adverse Events Reported With the Combinations of Seribantumab Plus Fulvestrant Versus Fulvestrant Alone Patients with any TEAE-Serious Adverse event	1 participants	0 participants
Number of Participants With Treatment-emergent Adverse Events Reported With the Combinations of Seribantumab Plus Fulvestrant Versus Fulvestrant Alone NCI-CTCAE Grade 3 or Higher	2 participants	1 participants

SECONDARY outcome

Population: Safety Population: The safety population includes patients receiving at least one dose of study medication. All safety analyses were be performed on this population.

Outcome measures

Outcome measures
Measure	Arm A (Experimental): Seribantumab and Fulvestrant n=11 Participants Seribantumab (a human monoclonal antibody that targets ErbB3, a cell surface receptor that is activated by the ligand heregulin. Heregulin-driven ErbB3 signaling has been implicated as a mechanism of tumor growth and resistance to targeted, cytotoxic and anti-endocrine therapies. When used in the combination setting, seribantumab is designed to block ErbB3 signaling in order to enhance the anti-tumor effect of a combination therapy partner): fixed dose of 3000 mg intravenously (IV) on day 1 and 15 of each 28-day cycle Fulvestrant (a drug treatment of hormone receptor-positive metastatic breast cancer in post-menopausal women with disease progression following anti-estrogen therapy. It is an estrogen receptor antagonist with no agonist effects, which works both by down-regulating and by degrading the estrogen receptor): 500 mg intramuscularly (IM) on Days 1 and 15 of Cycle 1, and then on Day 1 of each subsequent 28 day cycle	Arm B (Control): Placebo and Fulvestrant n=11 Participants Placebo: intravenously (IV) on day 1 and 15 of each 28-day cycle Fulvestrant: (a drug treatment of hormone receptor-positive metastatic breast cancer in post-menopausal women with disease progression following anti-estrogen therapy. It is an estrogen receptor antagonist with no agonist effects, which works both by down-regulating and by degrading the estrogen receptor): 500 mg intramuscularly (IM) on Days 1 and 15 of Cycle 1, and then on Day 1 of each subsequent 28 day cycle
Percentage of Treatment-emergent Adverse Events Reported With the Combinations of Seribantumab Plus Fulvestrant Versus Fulvestrant Alone TEAE-Serious Adverse event	9.1 percentage of adverse events	0 percentage of adverse events
Percentage of Treatment-emergent Adverse Events Reported With the Combinations of Seribantumab Plus Fulvestrant Versus Fulvestrant Alone TEAE-Related	63.6 percentage of adverse events	36.4 percentage of adverse events
Percentage of Treatment-emergent Adverse Events Reported With the Combinations of Seribantumab Plus Fulvestrant Versus Fulvestrant Alone NCI-CTCAE Grade 3 or Higher	18.2 percentage of adverse events	9.1 percentage of adverse events

SECONDARY outcome

Timeframe: The study terminated prematurely after 13 months. Were to be analyzed post-dose on Cycle 1,Week 1 & pre-dose for all subsequent seribantumab infusions until the completion of Cycle 2. Fulvestrant PK samples were to be collected prior to seribantumab dose

Population: Due to the premature study termination, the PK data were not collected. There was no pharmacokinetic data feasible for the analysis, and as such, no related analyses were performed. Hence, data could not be reported in the data table.

Pharmacokinetic (PK) evaluation are performed on samples obtained pre-dose on day 1 and 15 of each 28-day cycle to assess pre-treatment trough concentrations of MM-121. The maximum observed concentration (Cmax) is presented and calculated usig Non-compartmental analysis (NCA). Serum levels of MM-121 are measured at a central lab using an enzyme-linked immunosorbent assay (ELISA).

Outcome measures

Outcome data not reported

Adverse Events

Arm A (Experimental): Seribantumab and Fulvestrant

Serious events: 1 serious events

Other events: 10 other events

Deaths: 10 deaths

Arm B (Control): Placebo and Fulvestrant

Serious events: 0 serious events

Other events: 8 other events

Deaths: 10 deaths

Serious adverse events

Serious adverse events
Measure	Arm A (Experimental): Seribantumab and Fulvestrant n=11 participants at risk Seribantumab (a human monoclonal antibody that targets ErbB3, a cell surface receptor that is activated by the ligand heregulin. Heregulin-driven ErbB3 signaling has been implicated as a mechanism of tumor growth and resistance to targeted, cytotoxic and anti-endocrine therapies. When used in the combination setting, seribantumab is designed to block ErbB3 signaling in order to enhance the anti-tumor effect of a combination therapy partner): fixed dose of 3000 mg intravenously (IV) on day 1 and 15 of each 28-day cycle Fulvestrant (a drug treatment of hormone receptor-positive metastatic breast cancer in post-menopausal women with disease progression following anti-estrogen therapy. It is an estrogen receptor antagonist with no agonist effects, which works both by down-regulating and by degrading the estrogen receptor): 500 mg intramuscularly (IM) on Days 1 and 15 of Cycle 1, and then on Day 1 of each subsequent 28 day cycle	Arm B (Control): Placebo and Fulvestrant n=11 participants at risk Placebo: intravenously (IV) on day 1 and 15 of each 28-day cycle Fulvestrant: (a drug treatment of hormone receptor-positive metastatic breast cancer in post-menopausal women with disease progression following anti-estrogen therapy. It is an estrogen receptor antagonist with no agonist effects, which works both by down-regulating and by degrading the estrogen receptor): 500 mg intramuscularly (IM) on Days 1 and 15 of Cycle 1, and then on Day 1 of each subsequent 28 day cycle
Musculoskeletal and connective tissue disorders Arthralgia	9.1% 1/11 • Number of events 1 • From Baseline through to premature study completion up to 13 months (30 Nov 2018) The safety population includes patients receiving at least one dose of study medication. All safety analyses were be performed on this population. Safety analyses (adverse events and laboratory analyses) were performed using the safety population. Adverse events were coded using the latest MedDRA dictionary (MedDRA 21.0). Severity of adverse events was graded according to the NCI CTCAE version 4.03.	0.00% 0/11 • From Baseline through to premature study completion up to 13 months (30 Nov 2018) The safety population includes patients receiving at least one dose of study medication. All safety analyses were be performed on this population. Safety analyses (adverse events and laboratory analyses) were performed using the safety population. Adverse events were coded using the latest MedDRA dictionary (MedDRA 21.0). Severity of adverse events was graded according to the NCI CTCAE version 4.03.

Other adverse events

Additional Information

VP, Clinical Operations

Elevation oncology

Phone: +1-716 371 1125

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place