Trial Outcomes & Findings for Atezolizumab and Cobimetinib or Idasanutlin in Participants With Stage IV or Unresectable Recurrent Estrogen Receptor Positive Breast Cancer (NCT NCT03566485)

NCT ID: NCT03566485

Last Updated: 2021-08-11

Results Overview

Assessment of DLT for the patients in the atezolizumab and idasanutiln arm of the study

Recruitment status

TERMINATED

Study phase

PHASE1/PHASE2

Target enrollment

12 participants

Primary outcome timeframe

At 28 days

Results posted on

2021-08-11

Participant Flow

Participants were recruited to this study from July 2018 to November 2019 at Vanderbilt-Ingram Cancer Center in Nashville, TN. This study stopped early due to low accrual.

Twelve participants were enrolled onto this study.

Participant milestones

Participant milestones
Measure	Phase 2 (Atezolizumab, Cobimetinib) Participants with TP53 gene mutation receive atezolizumab IV over 60 minutes starting with day 15 of course 1 and then on days 1 and 15 of subsequent courses, and cobimetinib PO daily on days 1-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Atezolizumab: Given by IV Cobimetinib: Given by mouth	Phase 1b - (Atezolizumab, Idasanutlin) Atezolizumab: Given by IV Idasanutlin: Given by mouth
Overall Study STARTED	5	7
Overall Study COMPLETED	0	0
Overall Study NOT COMPLETED	5	7

Reasons for withdrawal

Reasons for withdrawal
Measure	Phase 2 (Atezolizumab, Cobimetinib) Participants with TP53 gene mutation receive atezolizumab IV over 60 minutes starting with day 15 of course 1 and then on days 1 and 15 of subsequent courses, and cobimetinib PO daily on days 1-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Atezolizumab: Given by IV Cobimetinib: Given by mouth	Phase 1b - (Atezolizumab, Idasanutlin) Atezolizumab: Given by IV Idasanutlin: Given by mouth
Overall Study Disease progression	5	4
Overall Study Clinical progression	0	1
Overall Study Toxicity	0	2

Baseline Characteristics

Atezolizumab and Cobimetinib or Idasanutlin in Participants With Stage IV or Unresectable Recurrent Estrogen Receptor Positive Breast Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Phase 2 (Atezolizumab, Cobimetinib) n=5 Participants Participants with TP53 gene mutation receive atezolizumab IV over 60 minutes starting with day 15 of course 1 and then on days 1 and 15 of subsequent courses, and cobimetinib PO daily on days 1-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Atezolizumab: Given by IV Cobimetinib: Given by mouth	Phase 1b - (Atezolizumab, Idasanutlin) n=7 Participants Atezolizumab: Given by IV Idasanutlin: Given by mouth	Total n=12 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	4 Participants n=5 Participants	5 Participants n=7 Participants	9 Participants n=5 Participants
Age, Categorical >=65 years	1 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants
Sex: Female, Male Female	5 Participants n=5 Participants	7 Participants n=7 Participants	12 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	4 Participants n=5 Participants	5 Participants n=7 Participants	9 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) White	4 Participants n=5 Participants	5 Participants n=7 Participants	9 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants
Region of Enrollment United States	5 participants n=5 Participants	7 participants n=7 Participants	12 participants n=5 Participants

PRIMARY outcome

Timeframe: At 28 days

Population: patients in the atezolizumab and idasanutiln arm of the study

Assessment of DLT for the patients in the atezolizumab and idasanutiln arm of the study

Outcome measures

Outcome measures
Measure	Phase 1b - (Atezolizumab, Idasanutlin) n=7 Participants Atezolizumab: Given by IV Idasanutlin: Given by mouth
Number of Participants With a Dose Limiting Toxicity (DLT) (Phase I)	1 Participants

PRIMARY outcome

Timeframe: At 28 days

Population: Patients in the atezolizumab and idasanutiln combination arm of the study. Dosage used: Atezolizumab 840mg IV + Idasanutlin 100mg PO

Assessment of MTD for the atezolizumab and idasanutiln combination arm of the study

Outcome measures

Outcome measures
Measure	Phase 1b - (Atezolizumab, Idasanutlin) n=7 Participants Atezolizumab: Given by IV Idasanutlin: Given by mouth
Maximum Tolerated Dose (Phase I)	NA mg Not enough patients were put on the Idasa + Atezo arm; therefore, unable to determine MTD. Dosage used: Atezolizumab 840mg IV + Idasanutlin 100mg PO.

PRIMARY outcome

Timeframe: At 28 days

Population: Patients on the atezolizumab and idasanutiln combination arm of the study. Dosage used: Atezolizumab 840mg IV + Idasanutlin 100mg PO.

Assessment of recommended phase II dose for the atezolizumab and idasanutiln combination arm of the study

Outcome measures

Outcome measures
Measure	Phase 1b - (Atezolizumab, Idasanutlin) n=7 Participants Atezolizumab: Given by IV Idasanutlin: Given by mouth
Recommended Phase II Dose (Phase I)	NA mg Not enough patients were put on the Idasa + Atezo arm; therefore, unable to determine MTD and recommend dose for phase II. Dosage used: Atezolizumab 840mg IV + Idasanutlin 100mg PO. For phase II, no patients were assigned to this arm.

PRIMARY outcome

Timeframe: Up to 28 days after completion of study treatment, for a total of 2 years

Population: Patients on Phase 2 Arm 1 (TP53-mut) - Atezolizumab 840mg IV + Cobimetinib 60mg PO

Assessment of clinical impact (anti-tumor effect) of the combination of atezolizumab and cobimetinib or idasanutiln in patients with metastatic ER \+ breast cancer by measure the rate (%) of complete and partial responses seen in patients with measurable disease. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.

Outcome measures

Outcome measures
Measure	Phase 1b - (Atezolizumab, Idasanutlin) n=5 Participants Atezolizumab: Given by IV Idasanutlin: Given by mouth
Overall Response Rate (ORR; by Response Evaluation Criteria in Solid Tumors [RECIST]1.1) (Phase II)	NA percentage of participants Among the 5 participants, two patients had only baseline measurements, one patient had only follow up measurement, and one patient did not have any measurements. Only one patient had progressive disease after baseline measurement. Therefore, not enough number of patients for calculating this outcome.

SECONDARY outcome

Timeframe: At 6 months

Population: patients on Phase 2 Arm 1 (TP53-mut) - Atezolizumab 840mg IV + Cobimetinib 60mg PO

Assessment of clinical impact (anti-tumor effect) of the combination of atezolizumab and cobimetinib or idasanutiln in patients with metastatic ER \+ breast cancer by measure the rate (%) of complete and partial responses + stability of disease at 6 months seen in patients with measurable disease. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.

Outcome measures

Outcome measures
Measure	Phase 1b - (Atezolizumab, Idasanutlin) n=5 Participants Atezolizumab: Given by IV Idasanutlin: Given by mouth
Clinical Benefit Rate (CBR) (Phase II)	NA percentage of participants Among 5 participants, two patients had only baseline measurements, one patient had only follow up measurement, and one patient did not have any measurements. Only one patient had progressive disease after baseline measurement. Therefore, not enough number of patients for calculating this outcome.

SECONDARY outcome

Timeframe: Up to 28 days after completion of study treatment, for a total of 2 years

Population: An insufficient number of participants exhibited response for analysis.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: At 12 months

Population: Patients on Phase 2 Arm 1 (TP53-mut) - Atezolizumab 840mg IV + Cobimetinib 60mg PO

Assessment of clinical impact (anti-tumor effect) of the combination of atezolizumab and cobimetinib or idasanutiln in patients with metastatic ER \+ breast cancer by measuring the interval (in months) between treatment initiation and disease progression. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1).

Outcome measures

Outcome measures
Measure	Phase 1b - (Atezolizumab, Idasanutlin) n=5 Participants Atezolizumab: Given by IV Idasanutlin: Given by mouth
Progression-free Survival (PFS) (Phase II) in Days	56 days Interval 51.0 to Could not be estimated from the data due to insufficient number of participants with events

SECONDARY outcome

Timeframe: At 12 months

Population: Patients on Phase 2 Arm 1 (TP53-mut) - Atezolizumab 840mg IV + Cobimetinib 60mg PO

Outcome measures

Outcome measures
Measure	Phase 1b - (Atezolizumab, Idasanutlin) n=5 Participants Atezolizumab: Given by IV Idasanutlin: Given by mouth
Overall Survival (OS) (Phase II) in Days	161 days Interval 136.0 to Could not be estimated from the data due to insufficient number of participants with events.

SECONDARY outcome

Timeframe: Up to 28 days after completion of study treatment, for a total of 2 years

Population: patients on atezolizumab and cobimetinib.

Assessment of adverse events throughout the phase II study

Outcome measures

Outcome measures
Measure	Phase 1b - (Atezolizumab, Idasanutlin) n=5 Participants Atezolizumab: Given by IV Idasanutlin: Given by mouth
Number of Adverse Events (Phase II)	99 events

Adverse Events

Phase 2 (Atezolizumab, Cobimetinib)

Serious events: 2 serious events

Other events: 5 other events

Deaths: 3 deaths

Phase 1b - (Atezolizumab, Idasanutlin)

Serious events: 4 serious events

Other events: 7 other events

Deaths: 3 deaths

Serious adverse events

Serious adverse events
Measure	Phase 2 (Atezolizumab, Cobimetinib) n=5 participants at risk Participants with TP53 gene mutation receive atezolizumab IV over 60 minutes starting with day 15 of course 1 and then on days 1 and 15 of subsequent courses, and cobimetinib PO daily on days 1-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Atezolizumab: Given by IV Cobimetinib: Given by mouth	Phase 1b - (Atezolizumab, Idasanutlin) n=7 participants at risk Atezolizumab: Given by IV Idasanutlin: Given by mouth
Musculoskeletal and connective tissue disorders Arthralgia	20.0% 1/5 • Number of events 1 • Initiation of study medication, throughout the study, and within 28 days (+/- 7 days) of the last dose of study medication, for a total of 2 years.	0.00% 0/7 • Initiation of study medication, throughout the study, and within 28 days (+/- 7 days) of the last dose of study medication, for a total of 2 years.
Musculoskeletal and connective tissue disorders Back pain	20.0% 1/5 • Number of events 1 • Initiation of study medication, throughout the study, and within 28 days (+/- 7 days) of the last dose of study medication, for a total of 2 years.	0.00% 0/7 • Initiation of study medication, throughout the study, and within 28 days (+/- 7 days) of the last dose of study medication, for a total of 2 years.
Investigations Neutrophil count decreased	20.0% 1/5 • Number of events 1 • Initiation of study medication, throughout the study, and within 28 days (+/- 7 days) of the last dose of study medication, for a total of 2 years.	28.6% 2/7 • Number of events 2 • Initiation of study medication, throughout the study, and within 28 days (+/- 7 days) of the last dose of study medication, for a total of 2 years.
Psychiatric disorders Suicide	0.00% 0/5 • Initiation of study medication, throughout the study, and within 28 days (+/- 7 days) of the last dose of study medication, for a total of 2 years.	14.3% 1/7 • Number of events 1 • Initiation of study medication, throughout the study, and within 28 days (+/- 7 days) of the last dose of study medication, for a total of 2 years.
Musculoskeletal and connective tissue disorders Osteonecrosis	0.00% 0/5 • Initiation of study medication, throughout the study, and within 28 days (+/- 7 days) of the last dose of study medication, for a total of 2 years.	14.3% 1/7 • Number of events 1 • Initiation of study medication, throughout the study, and within 28 days (+/- 7 days) of the last dose of study medication, for a total of 2 years.
Infections and infestations Strep infection	0.00% 0/5 • Initiation of study medication, throughout the study, and within 28 days (+/- 7 days) of the last dose of study medication, for a total of 2 years.	14.3% 1/7 • Number of events 1 • Initiation of study medication, throughout the study, and within 28 days (+/- 7 days) of the last dose of study medication, for a total of 2 years.
Gastrointestinal disorders Vomiting	0.00% 0/5 • Initiation of study medication, throughout the study, and within 28 days (+/- 7 days) of the last dose of study medication, for a total of 2 years.	14.3% 1/7 • Number of events 1 • Initiation of study medication, throughout the study, and within 28 days (+/- 7 days) of the last dose of study medication, for a total of 2 years.
Blood and lymphatic system disorders Febrile neutropenia	0.00% 0/5 • Initiation of study medication, throughout the study, and within 28 days (+/- 7 days) of the last dose of study medication, for a total of 2 years.	28.6% 2/7 • Number of events 2 • Initiation of study medication, throughout the study, and within 28 days (+/- 7 days) of the last dose of study medication, for a total of 2 years.
Investigations Platelet count decrease	0.00% 0/5 • Initiation of study medication, throughout the study, and within 28 days (+/- 7 days) of the last dose of study medication, for a total of 2 years.	28.6% 2/7 • Number of events 2 • Initiation of study medication, throughout the study, and within 28 days (+/- 7 days) of the last dose of study medication, for a total of 2 years.
Investigations White blood cell decreased	0.00% 0/5 • Initiation of study medication, throughout the study, and within 28 days (+/- 7 days) of the last dose of study medication, for a total of 2 years.	14.3% 1/7 • Number of events 1 • Initiation of study medication, throughout the study, and within 28 days (+/- 7 days) of the last dose of study medication, for a total of 2 years.
Blood and lymphatic system disorders Anemia	0.00% 0/5 • Initiation of study medication, throughout the study, and within 28 days (+/- 7 days) of the last dose of study medication, for a total of 2 years.	14.3% 1/7 • Number of events 1 • Initiation of study medication, throughout the study, and within 28 days (+/- 7 days) of the last dose of study medication, for a total of 2 years.
Infections and infestations Lung infection	0.00% 0/5 • Initiation of study medication, throughout the study, and within 28 days (+/- 7 days) of the last dose of study medication, for a total of 2 years.	14.3% 1/7 • Number of events 1 • Initiation of study medication, throughout the study, and within 28 days (+/- 7 days) of the last dose of study medication, for a total of 2 years.
Investigations Death	0.00% 0/5 • Initiation of study medication, throughout the study, and within 28 days (+/- 7 days) of the last dose of study medication, for a total of 2 years.	14.3% 1/7 • Number of events 1 • Initiation of study medication, throughout the study, and within 28 days (+/- 7 days) of the last dose of study medication, for a total of 2 years.

Other adverse events

Additional Information

Teresa Melton

Vanderbilt-Ingram Cancer Center

Phone: 6159367423

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place