Trial Outcomes & Findings for Phase I-II Study of Interferon-gamma in Patients With HER-2 Positive Breast Cancer (NCT NCT03112590)

Last Updated: 2023-04-19

Results Overview

The dose limiting toxicity (DLT) evaluation period for dose escalation will be during the first three weeks. The maximum tolerated dose (MTD) dose level is defined as the highest dose level with ≤1 out of 6 participants experiencing a DLT. If the first dose level experience two or more DLTs, then dose de-escalation will occur. DLT during cycle one (C1) is defined as follows: Non-hematologic or hematologic toxicities that are ≥ grade 3 in severity and probably or definitely related to study therapy which leads to chemotherapy treatment delays \> 14 days are considered DLT. The MTD will become the RP2D.

Recruitment status

COMPLETED

Study phase

PHASE1/PHASE2

Target enrollment

51 participants

Primary outcome timeframe

12 weeks

Results posted on

2023-04-19

Participant Flow

Participant milestones

Participant milestones
Measure	Phase 1 Level 1 Interferon-gamma (IFN-γ): Phase 1: IFN-γ 50 mcg/m\^2 SQ x 3 days/week for 12 weeks. Paclitaxel: Phase 1 and Phase 2: Paclitaxel 80 mg/m\^2/week, for 12 weeks. Trastuzumab: Phase 1 and Phase 2: Trastuzumab 8 mg/kg intravenous (IV) loading dose on cycle 1/day 1 (C1D1), followed by 6 mg/kg on subsequent cycles every 3 weeks, for 12 weeks. Pertuzumab: Phase 1 and Phase 2: Pertuzumab 840 mg IV loading dose on C1D1, followed by 420 mg on subsequent cycles every 3 weeks, for 12 weeks.	Phase 1 Level 2 Interferon-gamma (IFN-γ): Phase 1: IFN-γ 75 mcg/m\^2 SQ x 3 days/week for 12 weeks. Paclitaxel: Phase 1 and Phase 2: Paclitaxel 80 mg/m\^2/week, for 12 weeks. Trastuzumab: Phase 1 and Phase 2: Trastuzumab 8 mg/kg intravenous (IV) loading dose on cycle 1/day 1 (C1D1), followed by 6 mg/kg on subsequent cycles every 3 weeks, for 12 weeks. Pertuzumab: Phase 1 and Phase 2: Pertuzumab 840 mg IV loading dose on C1D1, followed by 420 mg on subsequent cycles every 3 weeks, for 12 weeks.	Phase 2 Interferon-gamma (IFN-γ): Phase 2: IFN-γ 75 mcg/m\^2 SQ x 3 days/week for 12 weeks. Paclitaxel: Phase 1 and Phase 2: Paclitaxel 80 mg/m\^2/week, for 12 weeks. Trastuzumab: Phase 1 and Phase 2: Trastuzumab 8 mg/kg intravenous (IV) loading dose on cycle 1/day 1 (C1D1), followed by 6 mg/kg on subsequent cycles every 3 weeks, for 12 weeks. Pertuzumab: Phase 1 and Phase 2: Pertuzumab 840 mg IV loading dose on C1D1, followed by 420 mg on subsequent cycles every 3 weeks, for 12 weeks.
Overall Study STARTED	3	6	42
Overall Study COMPLETED	3	5	42
Overall Study NOT COMPLETED	0	1	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Phase 1 Level 1 Interferon-gamma (IFN-γ): Phase 1: IFN-γ 50 mcg/m\^2 SQ x 3 days/week for 12 weeks. Paclitaxel: Phase 1 and Phase 2: Paclitaxel 80 mg/m\^2/week, for 12 weeks. Trastuzumab: Phase 1 and Phase 2: Trastuzumab 8 mg/kg intravenous (IV) loading dose on cycle 1/day 1 (C1D1), followed by 6 mg/kg on subsequent cycles every 3 weeks, for 12 weeks. Pertuzumab: Phase 1 and Phase 2: Pertuzumab 840 mg IV loading dose on C1D1, followed by 420 mg on subsequent cycles every 3 weeks, for 12 weeks.	Phase 1 Level 2 Interferon-gamma (IFN-γ): Phase 1: IFN-γ 75 mcg/m\^2 SQ x 3 days/week for 12 weeks. Paclitaxel: Phase 1 and Phase 2: Paclitaxel 80 mg/m\^2/week, for 12 weeks. Trastuzumab: Phase 1 and Phase 2: Trastuzumab 8 mg/kg intravenous (IV) loading dose on cycle 1/day 1 (C1D1), followed by 6 mg/kg on subsequent cycles every 3 weeks, for 12 weeks. Pertuzumab: Phase 1 and Phase 2: Pertuzumab 840 mg IV loading dose on C1D1, followed by 420 mg on subsequent cycles every 3 weeks, for 12 weeks.	Phase 2 Interferon-gamma (IFN-γ): Phase 2: IFN-γ 75 mcg/m\^2 SQ x 3 days/week for 12 weeks. Paclitaxel: Phase 1 and Phase 2: Paclitaxel 80 mg/m\^2/week, for 12 weeks. Trastuzumab: Phase 1 and Phase 2: Trastuzumab 8 mg/kg intravenous (IV) loading dose on cycle 1/day 1 (C1D1), followed by 6 mg/kg on subsequent cycles every 3 weeks, for 12 weeks. Pertuzumab: Phase 1 and Phase 2: Pertuzumab 840 mg IV loading dose on C1D1, followed by 420 mg on subsequent cycles every 3 weeks, for 12 weeks.
Overall Study Adverse Event	0	1	0

Baseline Characteristics

Phase I-II Study of Interferon-gamma in Patients With HER-2 Positive Breast Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Phase 1 Level 1 n=3 Participants Interferon-gamma (IFN-γ): Phase 1: IFN-γ 50 mcg/m\^2 SQ x 3 days/week for 12 weeks. Paclitaxel: Phase 1 and Phase 2: Paclitaxel 80 mg/m\^2/week, for 12 weeks. Trastuzumab: Phase 1 and Phase 2: Trastuzumab 8 mg/kg intravenous (IV) loading dose on cycle 1/day 1 (C1D1), followed by 6 mg/kg on subsequent cycles every 3 weeks, for 12 weeks. Pertuzumab: Phase 1 and Phase 2: Pertuzumab 840 mg IV loading dose on C1D1, followed by 420 mg on subsequent cycles every 3 weeks, for 12 weeks.	Phase 1 Level 2 n=6 Participants Interferon-gamma (IFN-γ): Phase 1: IFN-γ 75 mcg/m\^2 SQ x 3 days/week for 12 weeks. Paclitaxel: Phase 1 and Phase 2: Paclitaxel 80 mg/m\^2/week, for 12 weeks. Trastuzumab: Phase 1 and Phase 2: Trastuzumab 8 mg/kg intravenous (IV) loading dose on cycle 1/day 1 (C1D1), followed by 6 mg/kg on subsequent cycles every 3 weeks, for 12 weeks. Pertuzumab: Phase 1 and Phase 2: Pertuzumab 840 mg IV loading dose on C1D1, followed by 420 mg on subsequent cycles every 3 weeks, for 12 weeks.	Phase 2 n=42 Participants Interferon-gamma (IFN-γ): Phase 2: IFN-γ 75 mcg/m\^2 SQ x 3 days/week for 12 weeks. Paclitaxel: Phase 1 and Phase 2: Paclitaxel 80 mg/m\^2/week, for 12 weeks. Trastuzumab: Phase 1 and Phase 2: Trastuzumab 8 mg/kg intravenous (IV) loading dose on cycle 1/day 1 (C1D1), followed by 6 mg/kg on subsequent cycles every 3 weeks, for 12 weeks. Pertuzumab: Phase 1 and Phase 2: Pertuzumab 840 mg IV loading dose on C1D1, followed by 420 mg on subsequent cycles every 3 weeks, for 12 weeks.	Total n=51 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
Age, Categorical Between 18 and 65 years	3 Participants n=5 Participants	6 Participants n=7 Participants	28 Participants n=5 Participants	37 Participants n=4 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	14 Participants n=5 Participants	14 Participants n=4 Participants
Sex: Female, Male Female	3 Participants n=5 Participants	6 Participants n=7 Participants	42 Participants n=5 Participants	51 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
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	0 Participants n=7 Participants	5 Participants n=5 Participants	5 Participants n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	3 Participants n=5 Participants	6 Participants n=7 Participants	37 Participants n=5 Participants	46 Participants n=4 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 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
Race (NIH/OMB) Asian	0 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants	4 Participants n=4 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
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants
Race (NIH/OMB) White	3 Participants n=5 Participants	3 Participants n=7 Participants	37 Participants n=5 Participants	43 Participants n=4 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
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	3 Participants n=5 Participants	3 Participants n=4 Participants
Region of Enrollment United States	3 participants n=5 Participants	6 participants n=7 Participants	42 participants n=5 Participants	51 participants n=4 Participants

PRIMARY outcome

Timeframe: 12 weeks

Outcome measures

Outcome measures
Measure	Combination Therapy n=9 Participants Interferon-gamma (IFN-γ): Phase 1: IFN-γ 50 or 75 mcg/m\^2 SQ x 3 days/week for 12 weeks. Phase 2: IFN-γ at Recommended Phase II Dose (RP2D) subcutaneously (SQ) x 3 days/week, for 12 weeks. Paclitaxel: Phase 1 and Phase 2: Paclitaxel 80 mg/m\^2/week, for 12 weeks. Trastuzumab: Phase 1 and Phase 2: Trastuzumab 8 mg/kg intravenous (IV) loading dose on cycle 1/day 1 (C1D1), followed by 6 mg/kg on subsequent cycles every 3 weeks, for 12 weeks. Pertuzumab: Phase 1 and Phase 2: Pertuzumab 840 mg IV loading dose on C1D1, followed by 420 mg on subsequent cycles every 3 weeks, for 12 weeks.
Phase 1: Recommended Phase 2 Dose (RP2D)	75 mcg/m^2

PRIMARY outcome

Timeframe: After post therapy surgery - Therapy: approximately 12 weeks per participant

Population: Evaluable participants

Pathologic complete response in the breast at definitive surgery after completion of protocol therapy. The pathologic response to treatment will be assessed by an institutional pathologist at Moffitt Cancer Center. The pathologist will evaluate response by the "Residual Cancer Burden"(RCB) for each participant as described in the online calculator (see RCB link in the More Information section). pCR is defined as no residual invasive carcinoma in the breast and lymph notes at definitive surgery following neoadjuvant therapy

Outcome measures

Outcome measures
Measure	Combination Therapy n=23 Participants Interferon-gamma (IFN-γ): Phase 1: IFN-γ 50 or 75 mcg/m\^2 SQ x 3 days/week for 12 weeks. Phase 2: IFN-γ at Recommended Phase II Dose (RP2D) subcutaneously (SQ) x 3 days/week, for 12 weeks. Paclitaxel: Phase 1 and Phase 2: Paclitaxel 80 mg/m\^2/week, for 12 weeks. Trastuzumab: Phase 1 and Phase 2: Trastuzumab 8 mg/kg intravenous (IV) loading dose on cycle 1/day 1 (C1D1), followed by 6 mg/kg on subsequent cycles every 3 weeks, for 12 weeks. Pertuzumab: Phase 1 and Phase 2: Pertuzumab 840 mg IV loading dose on C1D1, followed by 420 mg on subsequent cycles every 3 weeks, for 12 weeks.
Phase 2: Pathologic Complete Response Rate (pCR)	52 percentage of participants

SECONDARY outcome

Timeframe: 12 weeks

Population: Evaluable participants

Complete Response (CR) and Partial Response (PR) based upon tumor measurements obtained on physical examination at baseline, after completion of 4 cycles of study therapy. Factors that will be evaluated include: Breast mass(es) - size (longest dimension); Axillary lymph node(s) - size (longest dimension); Skin edema of the breast - present worse, present unchanged, present improved, or absent; Skin erythema of the breast - present worse, present unchanged, present improved, or absent.

Outcome measures

Outcome measures
Measure	Combination Therapy n=39 Participants Interferon-gamma (IFN-γ): Phase 1: IFN-γ 50 or 75 mcg/m\^2 SQ x 3 days/week for 12 weeks. Phase 2: IFN-γ at Recommended Phase II Dose (RP2D) subcutaneously (SQ) x 3 days/week, for 12 weeks. Paclitaxel: Phase 1 and Phase 2: Paclitaxel 80 mg/m\^2/week, for 12 weeks. Trastuzumab: Phase 1 and Phase 2: Trastuzumab 8 mg/kg intravenous (IV) loading dose on cycle 1/day 1 (C1D1), followed by 6 mg/kg on subsequent cycles every 3 weeks, for 12 weeks. Pertuzumab: Phase 1 and Phase 2: Pertuzumab 840 mg IV loading dose on C1D1, followed by 420 mg on subsequent cycles every 3 weeks, for 12 weeks.
Phase 2: Clinical Response Complete Response	25 Participants
Phase 2: Clinical Response Partial Response	11 Participants
Phase 2: Clinical Response Stable Disease	2 Participants
Phase 2: Clinical Response Progressive Disease	1 Participants

SECONDARY outcome

Timeframe: Up to 2 years

Population: Evaluable participants

Progression will be evaluated in this study using the Response Evaluation Criteria in Solid Tumors (RECIST) criteria, version 1.1. PFS is defined as the time from study therapy to the first occurrence of ipsilateral invasive breast tumor recurrence, ipsilateral locoregional invasive breast cancer recurrence, contralateral invasive breast cancer, distant recurrence, or death from any cause. This is reported as number of participants who progressed.

Outcome measures

Outcome measures
Measure	Combination Therapy n=39 Participants Interferon-gamma (IFN-γ): Phase 1: IFN-γ 50 or 75 mcg/m\^2 SQ x 3 days/week for 12 weeks. Phase 2: IFN-γ at Recommended Phase II Dose (RP2D) subcutaneously (SQ) x 3 days/week, for 12 weeks. Paclitaxel: Phase 1 and Phase 2: Paclitaxel 80 mg/m\^2/week, for 12 weeks. Trastuzumab: Phase 1 and Phase 2: Trastuzumab 8 mg/kg intravenous (IV) loading dose on cycle 1/day 1 (C1D1), followed by 6 mg/kg on subsequent cycles every 3 weeks, for 12 weeks. Pertuzumab: Phase 1 and Phase 2: Pertuzumab 840 mg IV loading dose on C1D1, followed by 420 mg on subsequent cycles every 3 weeks, for 12 weeks.
Phase 2: Progression Free Survival (PFS)/Number of Participants Who Progressed	1 participants

Adverse Events

Phase 1 Level 1

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Phase 1 Level 2

Serious events: 2 serious events

Other events: 6 other events

Deaths: 0 deaths

Phase 2

Serious events: 2 serious events

Other events: 4 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Phase 1 Level 1 n=3 participants at risk Interferon-gamma (IFN-γ): Phase 1: IFN-γ 50 mcg/m\^2 SQ x 3 days/week for 12 weeks. Paclitaxel: Phase 1 and Phase 2: Paclitaxel 80 mg/m\^2/week, for 12 weeks. Trastuzumab: Phase 1 and Phase 2: Trastuzumab 8 mg/kg intravenous (IV) loading dose on cycle 1/day 1 (C1D1), followed by 6 mg/kg on subsequent cycles every 3 weeks, for 12 weeks. Pertuzumab: Phase 1 and Phase 2: Pertuzumab 840 mg IV loading dose on C1D1, followed by 420 mg on subsequent cycles every 3 weeks, for 12 weeks.	Phase 1 Level 2 n=6 participants at risk Interferon-gamma (IFN-γ): Phase 1: IFN-γ 75 mcg/m\^2 SQ x 3 days/week for 12 weeks. Paclitaxel: Phase 1 and Phase 2: Paclitaxel 80 mg/m\^2/week, for 12 weeks. Trastuzumab: Phase 1 and Phase 2: Trastuzumab 8 mg/kg intravenous (IV) loading dose on cycle 1/day 1 (C1D1), followed by 6 mg/kg on subsequent cycles every 3 weeks, for 12 weeks. Pertuzumab: Phase 1 and Phase 2: Pertuzumab 840 mg IV loading dose on C1D1, followed by 420 mg on subsequent cycles every 3 weeks, for 12 weeks.	Phase 2 n=42 participants at risk Interferon-gamma (IFN-γ): Phase 2: IFN-γ 75 mcg/m\^2 SQ x 3 days/week for 12 weeks. Paclitaxel: Phase 1 and Phase 2: Paclitaxel 80 mg/m\^2/week, for 12 weeks. Trastuzumab: Phase 1 and Phase 2: Trastuzumab 8 mg/kg intravenous (IV) loading dose on cycle 1/day 1 (C1D1), followed by 6 mg/kg on subsequent cycles every 3 weeks, for 12 weeks. Pertuzumab: Phase 1 and Phase 2: Pertuzumab 840 mg IV loading dose on C1D1, followed by 420 mg on subsequent cycles every 3 weeks, for 12 weeks.
Cardiac disorders Sinus tachycardia	0.00% 0/3 • Adverse events were collected from date of on study to 30 days after last dose of study treatment, up to 4 months.	16.7% 1/6 • Number of events 1 • Adverse events were collected from date of on study to 30 days after last dose of study treatment, up to 4 months.	2.4% 1/42 • Number of events 1 • Adverse events were collected from date of on study to 30 days after last dose of study treatment, up to 4 months.
Respiratory, thoracic and mediastinal disorders Dyspnea	0.00% 0/3 • Adverse events were collected from date of on study to 30 days after last dose of study treatment, up to 4 months.	16.7% 1/6 • Number of events 1 • Adverse events were collected from date of on study to 30 days after last dose of study treatment, up to 4 months.	2.4% 1/42 • Number of events 1 • Adverse events were collected from date of on study to 30 days after last dose of study treatment, up to 4 months.
Vascular disorders Hypertension	0.00% 0/3 • Adverse events were collected from date of on study to 30 days after last dose of study treatment, up to 4 months.	0.00% 0/6 • Adverse events were collected from date of on study to 30 days after last dose of study treatment, up to 4 months.	2.4% 1/42 • Number of events 1 • Adverse events were collected from date of on study to 30 days after last dose of study treatment, up to 4 months.
Gastrointestinal disorders Gastritis	0.00% 0/3 • Adverse events were collected from date of on study to 30 days after last dose of study treatment, up to 4 months.	0.00% 0/6 • Adverse events were collected from date of on study to 30 days after last dose of study treatment, up to 4 months.	2.4% 1/42 • Number of events 1 • Adverse events were collected from date of on study to 30 days after last dose of study treatment, up to 4 months.
Gastrointestinal disorders Hemorrhoids	0.00% 0/3 • Adverse events were collected from date of on study to 30 days after last dose of study treatment, up to 4 months.	0.00% 0/6 • Adverse events were collected from date of on study to 30 days after last dose of study treatment, up to 4 months.	2.4% 1/42 • Number of events 1 • Adverse events were collected from date of on study to 30 days after last dose of study treatment, up to 4 months.
Cardiac disorders Heart failure	0.00% 0/3 • Adverse events were collected from date of on study to 30 days after last dose of study treatment, up to 4 months.	0.00% 0/6 • Adverse events were collected from date of on study to 30 days after last dose of study treatment, up to 4 months.	2.4% 1/42 • Number of events 1 • Adverse events were collected from date of on study to 30 days after last dose of study treatment, up to 4 months.
Respiratory, thoracic and mediastinal disorders Pneumonitis	0.00% 0/3 • Adverse events were collected from date of on study to 30 days after last dose of study treatment, up to 4 months.	0.00% 0/6 • Adverse events were collected from date of on study to 30 days after last dose of study treatment, up to 4 months.	2.4% 1/42 • Number of events 1 • Adverse events were collected from date of on study to 30 days after last dose of study treatment, up to 4 months.
Gastrointestinal disorders Diarrhea	0.00% 0/3 • Adverse events were collected from date of on study to 30 days after last dose of study treatment, up to 4 months.	16.7% 1/6 • Number of events 1 • Adverse events were collected from date of on study to 30 days after last dose of study treatment, up to 4 months.	0.00% 0/42 • Adverse events were collected from date of on study to 30 days after last dose of study treatment, up to 4 months.
Respiratory, thoracic and mediastinal disorders Respiratory, thoracic and mediastinal disorders - Other	0.00% 0/3 • Adverse events were collected from date of on study to 30 days after last dose of study treatment, up to 4 months.	16.7% 1/6 • Number of events 1 • Adverse events were collected from date of on study to 30 days after last dose of study treatment, up to 4 months.	0.00% 0/42 • Adverse events were collected from date of on study to 30 days after last dose of study treatment, up to 4 months.
Respiratory, thoracic and mediastinal disorders Wheezing	0.00% 0/3 • Adverse events were collected from date of on study to 30 days after last dose of study treatment, up to 4 months.	16.7% 1/6 • Number of events 1 • Adverse events were collected from date of on study to 30 days after last dose of study treatment, up to 4 months.	0.00% 0/42 • Adverse events were collected from date of on study to 30 days after last dose of study treatment, up to 4 months.
General disorders Fever	0.00% 0/3 • Adverse events were collected from date of on study to 30 days after last dose of study treatment, up to 4 months.	16.7% 1/6 • Number of events 1 • Adverse events were collected from date of on study to 30 days after last dose of study treatment, up to 4 months.	0.00% 0/42 • Adverse events were collected from date of on study to 30 days after last dose of study treatment, up to 4 months.
Gastrointestinal disorders Abdominal pain	0.00% 0/3 • Adverse events were collected from date of on study to 30 days after last dose of study treatment, up to 4 months.	16.7% 1/6 • Number of events 1 • Adverse events were collected from date of on study to 30 days after last dose of study treatment, up to 4 months.	0.00% 0/42 • Adverse events were collected from date of on study to 30 days after last dose of study treatment, up to 4 months.
Respiratory, thoracic and mediastinal disorders Laryngeal inflammation	0.00% 0/3 • Adverse events were collected from date of on study to 30 days after last dose of study treatment, up to 4 months.	16.7% 1/6 • Number of events 1 • Adverse events were collected from date of on study to 30 days after last dose of study treatment, up to 4 months.	0.00% 0/42 • Adverse events were collected from date of on study to 30 days after last dose of study treatment, up to 4 months.

Other adverse events

Additional Information

Hyo S. Han, MD

Moffitt Cancer Center

Phone: 813-745-4933

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place