Trial Outcomes & Findings for Neoadjuvant MEDI4736 Concomitant With Weekly Nab-paclitaxel and Dose-dense AC for Stage I-III Triple Negative Breast Cancer (NCT NCT02489448)

Last Updated: 2022-10-26

Results Overview

Pathologic response will be assessed in the surgically resected cancer and lymph nodes after completion of all chemotherapy by the local pathologist as part of routine care. Pathologic complete response is defined as no invasive cancer in the resected breast tissue and lymph nodes (ypT0/Tis, ypN0). The outcome was changed from 19 weeks at the time of results entry as the treatment period was actually 20 weeks and the outcome was assessed 4-6 weeks after treatment when surgery took place.

Recruitment status

COMPLETED

Study phase

PHASE1/PHASE2

Target enrollment

68 participants

Primary outcome timeframe

Up to 26 weeks

Results posted on

2022-10-26

Participant Flow

7 patients took part in the Phase 1 portion of the study. 61 patients took part in the Phase 2 portion of this study, for which results are presented. 2 removed consent once placed on study.

Participant milestones

Participant milestones
Measure	MEDI4736 The investigational product is MEDI4736 which will be supplied in glass vials containing 500 mg of liquid solution at a concentration of 50 mg/mL for intravenous (IV) administration. Routine, standard of care chemotherapy will be given together with the investigational product and will include weekly nab-paclitaxel x12 treatments followed by every two-week doxorubicin, cyclophosphamide (ddAC) x 4 treatments. MEDI4736: The investigational product is MEDI4736 which will be supplied in glass vials containing 500 mg of liquid solution at a concentration of 50 mg/mL for intravenous (IV) administration. Routine, standard of care chemotherapy will be given together with the investigational product and will include weekly nab-paclitaxel x12 treatments followed by every two-week doxorubicin, cyclophosphamide (ddAC) x 4 treatments.
Overall Study STARTED	68
Overall Study Phase 1 Started	7
Overall Study 3 mg Dose	4
Overall Study 10 mg Dose	3
Overall Study Phase 1 Completed	7
Overall Study Phase 2 Started	61
Overall Study Phase 2 Completed	56
Overall Study COMPLETED	63
Overall Study NOT COMPLETED	5

Reasons for withdrawal

Reasons for withdrawal
Measure	MEDI4736 The investigational product is MEDI4736 which will be supplied in glass vials containing 500 mg of liquid solution at a concentration of 50 mg/mL for intravenous (IV) administration. Routine, standard of care chemotherapy will be given together with the investigational product and will include weekly nab-paclitaxel x12 treatments followed by every two-week doxorubicin, cyclophosphamide (ddAC) x 4 treatments. MEDI4736: The investigational product is MEDI4736 which will be supplied in glass vials containing 500 mg of liquid solution at a concentration of 50 mg/mL for intravenous (IV) administration. Routine, standard of care chemotherapy will be given together with the investigational product and will include weekly nab-paclitaxel x12 treatments followed by every two-week doxorubicin, cyclophosphamide (ddAC) x 4 treatments.
Overall Study Death	3
Overall Study Withdrawal by Subject	2

Baseline Characteristics

Neoadjuvant MEDI4736 Concomitant With Weekly Nab-paclitaxel and Dose-dense AC for Stage I-III Triple Negative Breast Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Phase 1: 3mg MEDI4736 n=4 Participants The investigational product is MEDI4736 which will be supplied in glass vials containing 500 mg of liquid solution at a concentration of 50 mg/mL for intravenous (IV) administration. Routine, standard of care chemotherapy will be given together with the investigational product and will include weekly nab-paclitaxel x12 treatments followed by every two-week doxorubicin, cyclophosphamide (ddAC) x 4 treatments. MEDI4736: The investigational product is MEDI4736 which will be supplied in glass vials containing 500 mg of liquid solution at a concentration of 50 mg/mL for intravenous (IV) administration. Routine, standard of care chemotherapy will be given together with the investigational product and will include weekly nab-paclitaxel x12 treatments followed by every two-week doxorubicin, cyclophosphamide (ddAC) x 4 treatments.	Phase 1: 10mg MEDI4736 n=3 Participants The investigational product is MEDI4736 which will be supplied in glass vials containing 500 mg of liquid solution at a concentration of 50 mg/mL for intravenous (IV) administration. Routine, standard of care chemotherapy will be given together with the investigational product and will include weekly nab-paclitaxel x12 treatments followed by every two-week doxorubicin, cyclophosphamide (ddAC) x 4 treatments. MEDI4736: The investigational product is MEDI4736 which will be supplied in glass vials containing 500 mg of liquid solution at a concentration of 50 mg/mL for intravenous (IV) administration. Routine, standard of care chemotherapy will be given together with the investigational product and will include weekly nab-paclitaxel x12 treatments followed by every two-week doxorubicin, cyclophosphamide (ddAC) x 4 treatments.	Phase 2: 10mg MEDI4736 n=59 Participants The investigational product is MEDI4736 which will be supplied in glass vials containing 500 mg of liquid solution at a concentration of 50 mg/mL for intravenous (IV) administration. Routine, standard of care chemotherapy will be given together with the investigational product and will include weekly nab-paclitaxel x12 treatments followed by every two-week doxorubicin, cyclophosphamide (ddAC) x 4 treatments. MEDI4736: The investigational product is MEDI4736 which will be supplied in glass vials containing 500 mg of liquid solution at a concentration of 50 mg/mL for intravenous (IV) administration. Routine, standard of care chemotherapy will be given together with the investigational product and will include weekly nab-paclitaxel x12 treatments followed by every two-week doxorubicin, cyclophosphamide (ddAC) x 4 treatments.	Total n=66 Participants Total of all reporting groups
Age, Continuous	56 years n=5 Participants	50 years n=7 Participants	51 years n=5 Participants	51.5 years n=4 Participants
Sex: Female, Male Female	4 Participants n=5 Participants	3 Participants n=7 Participants	59 Participants n=5 Participants	66 Participants n=4 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
Race/Ethnicity, Customized Race/Ethnicity · White (non-Hispanic)	4 Participants n=5 Participants	2 Participants n=7 Participants	35 Participants n=5 Participants	41 Participants n=4 Participants
Race/Ethnicity, Customized Race/Ethnicity · Hispanic/Latino	0 Participants n=5 Participants	1 Participants n=7 Participants	5 Participants n=5 Participants	6 Participants n=4 Participants
Race/Ethnicity, Customized Race/Ethnicity · Black	0 Participants n=5 Participants	0 Participants n=7 Participants	11 Participants n=5 Participants	11 Participants n=4 Participants
Race/Ethnicity, Customized Race/Ethnicity · Asian/American Indian	0 Participants n=5 Participants	0 Participants n=7 Participants	4 Participants n=5 Participants	4 Participants n=4 Participants
Race/Ethnicity, Customized Race/Ethnicity · Unknown	0 Participants n=5 Participants	0 Participants n=7 Participants	4 Participants n=5 Participants	4 Participants n=4 Participants
Region of Enrollment United States	4 participants n=5 Participants	3 participants n=7 Participants	59 participants n=5 Participants	66 participants n=4 Participants

PRIMARY outcome

Timeframe: Up to 26 weeks

Population: 56 of 59 patients had surgery performed

Outcome measures

Outcome measures
Measure	MEDI4736 n=56 Participants The investigational product is MEDI4736 which will be supplied in glass vials containing 500 mg of liquid solution at a concentration of 50 mg/mL for intravenous (IV) administration. Routine, standard of care chemotherapy will be given together with the investigational product and will include weekly nab-paclitaxel x12 treatments followed by every two-week doxorubicin, cyclophosphamide (ddAC) x 4 treatments. MEDI4736: The investigational product is MEDI4736 which will be supplied in glass vials containing 500 mg of liquid solution at a concentration of 50 mg/mL for intravenous (IV) administration. Routine, standard of care chemotherapy will be given together with the investigational product and will include weekly nab-paclitaxel x12 treatments followed by every two-week doxorubicin, cyclophosphamide (ddAC) x 4 treatments.
Pathologic Complete Response (pCR)	25 Participants

Adverse Events

Phase 1: MEDI4736 3mg & 10mg

Serious events: 3 serious events

Other events: 7 other events

Deaths: 0 deaths

Phase 2: MEDI4736 10mg

Serious events: 23 serious events

Other events: 60 other events

Deaths: 3 deaths

Serious adverse events

Other adverse events

Additional Information

Lajos Pusztai, MD, DPhil Professor of Medicine (Medical Oncology)

Yale School of Medicine

Phone: (203) 737-8309

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Phase 1: MEDI4736 3mg & 10mg n=7 participants at risk The investigational product is MEDI4736 which will be supplied in glass vials containing 500 mg of liquid solution at a concentration of 50 mg/mL for intravenous (IV) administration. Routine, standard of care chemotherapy will be given together with the investigational product and will include weekly nab-paclitaxel x12 treatments followed by every two-week doxorubicin, cyclophosphamide (ddAC) x 4 treatments. MEDI4736: The investigational product is MEDI4736 which will be supplied in glass vials containing 500 mg of liquid solution at a concentration of 50 mg/mL for intravenous (IV) administration. Routine, standard of care chemotherapy will be given together with the investigational product and will include weekly nab-paclitaxel x12 treatments followed by every two-week doxorubicin, cyclophosphamide (ddAC) x 4 treatments.	Phase 2: MEDI4736 10mg n=61 participants at risk The investigational product is MEDI4736 which will be supplied in glass vials containing 500 mg of liquid solution at a concentration of 50 mg/mL for intravenous (IV) administration. Routine, standard of care chemotherapy will be given together with the investigational product and will include weekly nab-paclitaxel x12 treatments followed by every two-week doxorubicin, cyclophosphamide (ddAC) x 4 treatments. MEDI4736: The investigational product is MEDI4736 which will be supplied in glass vials containing 500 mg of liquid solution at a concentration of 50 mg/mL for intravenous (IV) administration. Routine, standard of care chemotherapy will be given together with the investigational product and will include weekly nab-paclitaxel x12 treatments followed by every two-week doxorubicin, cyclophosphamide (ddAC) x 4 treatments.
Blood and lymphatic system disorders Anemia	0.00% 0/7 • Up to 20 weeks Adverse events are reported for Phase 1 doses combined and Phase 2. At the time of data collection in Phase 1, adverse events were collected at the patient level, not at the dosing level.	1.6% 1/61 • Number of events 1 • Up to 20 weeks Adverse events are reported for Phase 1 doses combined and Phase 2. At the time of data collection in Phase 1, adverse events were collected at the patient level, not at the dosing level.
Blood and lymphatic system disorders Febrile neutropenia	14.3% 1/7 • Number of events 1 • Up to 20 weeks Adverse events are reported for Phase 1 doses combined and Phase 2. At the time of data collection in Phase 1, adverse events were collected at the patient level, not at the dosing level.	6.6% 4/61 • Number of events 6 • Up to 20 weeks Adverse events are reported for Phase 1 doses combined and Phase 2. At the time of data collection in Phase 1, adverse events were collected at the patient level, not at the dosing level.
Cardiac disorders Atrial fibrillation	0.00% 0/7 • Up to 20 weeks Adverse events are reported for Phase 1 doses combined and Phase 2. At the time of data collection in Phase 1, adverse events were collected at the patient level, not at the dosing level.	3.3% 2/61 • Number of events 2 • Up to 20 weeks Adverse events are reported for Phase 1 doses combined and Phase 2. At the time of data collection in Phase 1, adverse events were collected at the patient level, not at the dosing level.
Cardiac disorders Cardiac arrest	0.00% 0/7 • Up to 20 weeks Adverse events are reported for Phase 1 doses combined and Phase 2. At the time of data collection in Phase 1, adverse events were collected at the patient level, not at the dosing level.	1.6% 1/61 • Number of events 1 • Up to 20 weeks Adverse events are reported for Phase 1 doses combined and Phase 2. At the time of data collection in Phase 1, adverse events were collected at the patient level, not at the dosing level.
Endocrine disorders Hyperthyroidism	0.00% 0/7 • Up to 20 weeks Adverse events are reported for Phase 1 doses combined and Phase 2. At the time of data collection in Phase 1, adverse events were collected at the patient level, not at the dosing level.	1.6% 1/61 • Number of events 1 • Up to 20 weeks Adverse events are reported for Phase 1 doses combined and Phase 2. At the time of data collection in Phase 1, adverse events were collected at the patient level, not at the dosing level.
Gastrointestinal disorders Colitis	0.00% 0/7 • Up to 20 weeks Adverse events are reported for Phase 1 doses combined and Phase 2. At the time of data collection in Phase 1, adverse events were collected at the patient level, not at the dosing level.	3.3% 2/61 • Number of events 2 • Up to 20 weeks Adverse events are reported for Phase 1 doses combined and Phase 2. At the time of data collection in Phase 1, adverse events were collected at the patient level, not at the dosing level.
Gastrointestinal disorders Diarrhea	14.3% 1/7 • Number of events 1 • Up to 20 weeks Adverse events are reported for Phase 1 doses combined and Phase 2. At the time of data collection in Phase 1, adverse events were collected at the patient level, not at the dosing level.	4.9% 3/61 • Number of events 3 • Up to 20 weeks Adverse events are reported for Phase 1 doses combined and Phase 2. At the time of data collection in Phase 1, adverse events were collected at the patient level, not at the dosing level.
Gastrointestinal disorders Enterocolitis	0.00% 0/7 • Up to 20 weeks Adverse events are reported for Phase 1 doses combined and Phase 2. At the time of data collection in Phase 1, adverse events were collected at the patient level, not at the dosing level.	1.6% 1/61 • Number of events 1 • Up to 20 weeks Adverse events are reported for Phase 1 doses combined and Phase 2. At the time of data collection in Phase 1, adverse events were collected at the patient level, not at the dosing level.
General disorders Fever	0.00% 0/7 • Up to 20 weeks Adverse events are reported for Phase 1 doses combined and Phase 2. At the time of data collection in Phase 1, adverse events were collected at the patient level, not at the dosing level.	4.9% 3/61 • Number of events 3 • Up to 20 weeks Adverse events are reported for Phase 1 doses combined and Phase 2. At the time of data collection in Phase 1, adverse events were collected at the patient level, not at the dosing level.
Immune system disorders Autoimmune disorder	0.00% 0/7 • Up to 20 weeks Adverse events are reported for Phase 1 doses combined and Phase 2. At the time of data collection in Phase 1, adverse events were collected at the patient level, not at the dosing level.	1.6% 1/61 • Number of events 1 • Up to 20 weeks Adverse events are reported for Phase 1 doses combined and Phase 2. At the time of data collection in Phase 1, adverse events were collected at the patient level, not at the dosing level.
Infections and infestations Infections and infestations - Other, specify - Community Acquired Pneumonia	0.00% 0/7 • Up to 20 weeks Adverse events are reported for Phase 1 doses combined and Phase 2. At the time of data collection in Phase 1, adverse events were collected at the patient level, not at the dosing level.	1.6% 1/61 • Number of events 1 • Up to 20 weeks Adverse events are reported for Phase 1 doses combined and Phase 2. At the time of data collection in Phase 1, adverse events were collected at the patient level, not at the dosing level.
Infections and infestations Sinus tachycardia	0.00% 0/7 • Up to 20 weeks Adverse events are reported for Phase 1 doses combined and Phase 2. At the time of data collection in Phase 1, adverse events were collected at the patient level, not at the dosing level.	1.6% 1/61 • Number of events 1 • Up to 20 weeks Adverse events are reported for Phase 1 doses combined and Phase 2. At the time of data collection in Phase 1, adverse events were collected at the patient level, not at the dosing level.
Infections and infestations Sinusitis	0.00% 0/7 • Up to 20 weeks Adverse events are reported for Phase 1 doses combined and Phase 2. At the time of data collection in Phase 1, adverse events were collected at the patient level, not at the dosing level.	1.6% 1/61 • Number of events 1 • Up to 20 weeks Adverse events are reported for Phase 1 doses combined and Phase 2. At the time of data collection in Phase 1, adverse events were collected at the patient level, not at the dosing level.
Injury, poisoning and procedural complications Fall	0.00% 0/7 • Up to 20 weeks Adverse events are reported for Phase 1 doses combined and Phase 2. At the time of data collection in Phase 1, adverse events were collected at the patient level, not at the dosing level.	3.3% 2/61 • Number of events 2 • Up to 20 weeks Adverse events are reported for Phase 1 doses combined and Phase 2. At the time of data collection in Phase 1, adverse events were collected at the patient level, not at the dosing level.
Investigations Investigations - Other, specify - Diverticulitis	0.00% 0/7 • Up to 20 weeks Adverse events are reported for Phase 1 doses combined and Phase 2. At the time of data collection in Phase 1, adverse events were collected at the patient level, not at the dosing level.	1.6% 1/61 • Number of events 1 • Up to 20 weeks Adverse events are reported for Phase 1 doses combined and Phase 2. At the time of data collection in Phase 1, adverse events were collected at the patient level, not at the dosing level.
Metabolism and nutrition disorders Dehydration	14.3% 1/7 • Number of events 1 • Up to 20 weeks Adverse events are reported for Phase 1 doses combined and Phase 2. At the time of data collection in Phase 1, adverse events were collected at the patient level, not at the dosing level.	1.6% 1/61 • Number of events 1 • Up to 20 weeks Adverse events are reported for Phase 1 doses combined and Phase 2. At the time of data collection in Phase 1, adverse events were collected at the patient level, not at the dosing level.
Metabolism and nutrition disorders Hyponatremia	0.00% 0/7 • Up to 20 weeks Adverse events are reported for Phase 1 doses combined and Phase 2. At the time of data collection in Phase 1, adverse events were collected at the patient level, not at the dosing level.	1.6% 1/61 • Number of events 1 • Up to 20 weeks Adverse events are reported for Phase 1 doses combined and Phase 2. At the time of data collection in Phase 1, adverse events were collected at the patient level, not at the dosing level.
Nervous system disorders Stroke	0.00% 0/7 • Up to 20 weeks Adverse events are reported for Phase 1 doses combined and Phase 2. At the time of data collection in Phase 1, adverse events were collected at the patient level, not at the dosing level.	1.6% 1/61 • Number of events 1 • Up to 20 weeks Adverse events are reported for Phase 1 doses combined and Phase 2. At the time of data collection in Phase 1, adverse events were collected at the patient level, not at the dosing level.
Nervous system disorders Syncope	0.00% 0/7 • Up to 20 weeks Adverse events are reported for Phase 1 doses combined and Phase 2. At the time of data collection in Phase 1, adverse events were collected at the patient level, not at the dosing level.	1.6% 1/61 • Number of events 1 • Up to 20 weeks Adverse events are reported for Phase 1 doses combined and Phase 2. At the time of data collection in Phase 1, adverse events were collected at the patient level, not at the dosing level.
Psychiatric disorders Psychiatric disorders - Other, specify - Altered mental status.	0.00% 0/7 • Up to 20 weeks Adverse events are reported for Phase 1 doses combined and Phase 2. At the time of data collection in Phase 1, adverse events were collected at the patient level, not at the dosing level.	1.6% 1/61 • Number of events 2 • Up to 20 weeks Adverse events are reported for Phase 1 doses combined and Phase 2. At the time of data collection in Phase 1, adverse events were collected at the patient level, not at the dosing level.
Renal and urinary disorders Acute kidney injury	0.00% 0/7 • Up to 20 weeks Adverse events are reported for Phase 1 doses combined and Phase 2. At the time of data collection in Phase 1, adverse events were collected at the patient level, not at the dosing level.	3.3% 2/61 • Number of events 2 • Up to 20 weeks Adverse events are reported for Phase 1 doses combined and Phase 2. At the time of data collection in Phase 1, adverse events were collected at the patient level, not at the dosing level.
Renal and urinary disorders Renal and urinary disorders - Other, specify - Renal failure	0.00% 0/7 • Up to 20 weeks Adverse events are reported for Phase 1 doses combined and Phase 2. At the time of data collection in Phase 1, adverse events were collected at the patient level, not at the dosing level.	1.6% 1/61 • Number of events 1 • Up to 20 weeks Adverse events are reported for Phase 1 doses combined and Phase 2. At the time of data collection in Phase 1, adverse events were collected at the patient level, not at the dosing level.
Renal and urinary disorders Renal and urinary disorders - Other, specify - UTI	0.00% 0/7 • Up to 20 weeks Adverse events are reported for Phase 1 doses combined and Phase 2. At the time of data collection in Phase 1, adverse events were collected at the patient level, not at the dosing level.	1.6% 1/61 • Number of events 1 • Up to 20 weeks Adverse events are reported for Phase 1 doses combined and Phase 2. At the time of data collection in Phase 1, adverse events were collected at the patient level, not at the dosing level.
Respiratory, thoracic and mediastinal disorders Dyspnea	28.6% 2/7 • Number of events 2 • Up to 20 weeks Adverse events are reported for Phase 1 doses combined and Phase 2. At the time of data collection in Phase 1, adverse events were collected at the patient level, not at the dosing level.	1.6% 1/61 • Number of events 1 • Up to 20 weeks Adverse events are reported for Phase 1 doses combined and Phase 2. At the time of data collection in Phase 1, adverse events were collected at the patient level, not at the dosing level.
Skin and subcutaneous tissue disorders Skin and subcutaneous tissue disorders - Other, specify - Skin and subcutaneous tissue disorders- Ot	0.00% 0/7 • Up to 20 weeks Adverse events are reported for Phase 1 doses combined and Phase 2. At the time of data collection in Phase 1, adverse events were collected at the patient level, not at the dosing level.	1.6% 1/61 • Number of events 1 • Up to 20 weeks Adverse events are reported for Phase 1 doses combined and Phase 2. At the time of data collection in Phase 1, adverse events were collected at the patient level, not at the dosing level.
Vascular disorders Thromboembolic event	0.00% 0/7 • Up to 20 weeks Adverse events are reported for Phase 1 doses combined and Phase 2. At the time of data collection in Phase 1, adverse events were collected at the patient level, not at the dosing level.	4.9% 3/61 • Number of events 3 • Up to 20 weeks Adverse events are reported for Phase 1 doses combined and Phase 2. At the time of data collection in Phase 1, adverse events were collected at the patient level, not at the dosing level.
Vascular disorders Vascular disorders - Other, specify - Labile BP (SBP 50s - 190s).	0.00% 0/7 • Up to 20 weeks Adverse events are reported for Phase 1 doses combined and Phase 2. At the time of data collection in Phase 1, adverse events were collected at the patient level, not at the dosing level.	1.6% 1/61 • Number of events 2 • Up to 20 weeks Adverse events are reported for Phase 1 doses combined and Phase 2. At the time of data collection in Phase 1, adverse events were collected at the patient level, not at the dosing level.
Infections and infestations Nail infection	14.3% 1/7 • Number of events 1 • Up to 20 weeks Adverse events are reported for Phase 1 doses combined and Phase 2. At the time of data collection in Phase 1, adverse events were collected at the patient level, not at the dosing level.	0.00% 0/61 • Up to 20 weeks Adverse events are reported for Phase 1 doses combined and Phase 2. At the time of data collection in Phase 1, adverse events were collected at the patient level, not at the dosing level.