Trial Outcomes & Findings for Nelipepimut-S Plus GM-CSF Vaccine Therapy in Treating Patients With Breast Cancer (NCT NCT02636582)

NCT ID: NCT02636582

Last Updated: 2023-12-05

Results Overview

Change from baseline in the Mean percent of Nelipepimut-S-specific cytotoxic T lymphocyte response one-month post-surgical resection. Wilcoxon rank sum test exact P-value was used.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 43 participants
• Primary outcome timeframe: One-Month post-surgical resection from baseline
• Results posted on: 2023-12-05

Participant Flow

Females >/= 18 years with DCIS identified on core needle biopsy and at least 1cm area of radiographic abnormality.

Only patients with allele HLA-A2 eligible for randomization. 23-were HLA-A2 negative, 7 were HLA-A2 positive and of the 7: 4-withdrew once they received their results, 1- had disease progression, 1-opted for earlier surgery and 1- opted for earlier surgery when trial went on hold after consent.

Participant milestones

Measure	GM-CSF (Control) Immunoadjuvant GM-CSF	Nelipepimut-S (NPS+GM-CSF) Vaccine with immunogenic peptide nelipepimut-S+GM-CSF (NPS+GM-CSF)
Overall Study STARTED	4	9
Overall Study At Surgery	4	9
Overall Study 1- Month Post-Op	4	9
Overall Study 3-6 Months Post-Op	3	9
Overall Study COMPLETED	3	9
Overall Study NOT COMPLETED	1	0

Reasons for withdrawal

Measure	GM-CSF (Control) Immunoadjuvant GM-CSF	Nelipepimut-S (NPS+GM-CSF) Vaccine with immunogenic peptide nelipepimut-S+GM-CSF (NPS+GM-CSF)
Overall Study Surgical Pathology	1	0

Baseline Characteristics

Race and Ethnicity were not collected from any participant.

Baseline characteristics by cohort

Measure	Arm I GM-CSF n=4 Participants Immunoadjuvant GM-CSF	Arm II NPS+GM-CSF n=9 Participants Vaccine with immunogenic peptide nelipepimut-S+GM-CSF (NPS+GM-CSF)	Total n=13 Participants Total of all reporting groups
Age, Continuous	54.5 years n=4 Participants	57 years n=9 Participants	57 years n=13 Participants
Sex: Female, Male Female	4 Participants n=4 Participants	9 Participants n=9 Participants	13 Participants n=13 Participants
Sex: Female, Male Male	0 Participants n=4 Participants	0 Participants n=9 Participants	0 Participants n=13 Participants
Race and Ethnicity Not Collected	—	—	0 Participants Race and Ethnicity were not collected from any participant.
Region of Enrollment United States	4 participants n=4 Participants	9 participants n=9 Participants	13 participants n=13 Participants

PRIMARY outcome

Timeframe: One-Month post-surgical resection from baseline

Change from baseline in the Mean percent of Nelipepimut-S-specific cytotoxic T lymphocyte response one-month post-surgical resection. Wilcoxon rank sum test exact P-value was used.

Outcome measures

Measure	GM-CSF n=4 Participants Immunoadjuvant GM-CSF	NPS+GM-CSF n=9 Participants Vaccine with immunogenic peptide nelipepimut-S+GM-CSF (NPS+GM-CSF)
Mean Percent of Nelipepimut-S-specific Cytotoxic T Lymphocyte Response (E75)	0.09 percent of cytotoxic T lymphocytes Interval 0.0 to 0.15	0.02 percent of cytotoxic T lymphocytes Interval 0.0 to 0.14

SECONDARY outcome

Timeframe: Baseline to surgical resection, up to 5 weeks

Change from baseline in the iTILs at surgical resection. Wilcoxon rank sum test exact P-value was used.

Outcome measures

Measure	GM-CSF n=3 Participants Immunoadjuvant GM-CSF	NPS+GM-CSF n=5 Participants Vaccine with immunogenic peptide nelipepimut-S+GM-CSF (NPS+GM-CSF)
Intra-tumoral Tumor-infiltrating Lymphocytes (iTILs) Within the Basement Membrane	0 percent of iTILs Interval -0.5 to 3.0	0.5 percent of iTILs Interval -0.3 to 0.5

SECONDARY outcome

Timeframe: Baseline to surgical resection, up to 5 weeks

Change from baseline in the iTILs at surgical resection. Wilcoxon rank sum test exact P-value was used.

Outcome measures

Measure	GM-CSF n=3 Participants Immunoadjuvant GM-CSF	NPS+GM-CSF n=5 Participants Vaccine with immunogenic peptide nelipepimut-S+GM-CSF (NPS+GM-CSF)
Intra-tumoral Tumor-infiltrating Lymphocytes (iTILs)	0 percent of iTILs Interval -5.0 to 0.0	0 percent of iTILs Interval -17.5 to 14.5

SECONDARY outcome

Timeframe: Baseline to surgical resection, up to 5 weeks

Difference in HER2 Expression in Biopsy and Resection Specimens. Differences were assessed using a Fisher's exact test.

Outcome measures

Measure	GM-CSF n=4 Participants Immunoadjuvant GM-CSF	NPS+GM-CSF n=9 Participants Vaccine with immunogenic peptide nelipepimut-S+GM-CSF (NPS+GM-CSF)
Number of Participants With HER2 Expression in Biopsy and Resection Specimens HER2 expression - biopsy 1+	2 Participants	3 Participants
Number of Participants With HER2 Expression in Biopsy and Resection Specimens HER2 expression - biopsy 2+	2 Participants	0 Participants
Number of Participants With HER2 Expression in Biopsy and Resection Specimens HER2 expression - biopsy 3+	0 Participants	3 Participants
Number of Participants With HER2 Expression in Biopsy and Resection Specimens HER2 expression - biopsy Normal Breast Tissue	0 Participants	1 Participants
Number of Participants With HER2 Expression in Biopsy and Resection Specimens HER2 expression - biopsy Missing	0 Participants	3 Participants
Number of Participants With HER2 Expression in Biopsy and Resection Specimens HER2 expression - resection 1+	2 Participants	1 Participants
Number of Participants With HER2 Expression in Biopsy and Resection Specimens HER2 expression - resection 2+	1 Participants	1 Participants
Number of Participants With HER2 Expression in Biopsy and Resection Specimens HER2 expression - resection 3+	1 Participants	2 Participants
Number of Participants With HER2 Expression in Biopsy and Resection Specimens HER2 expression - resection Normal Breast Tissue	0 Participants	3 Participants
Number of Participants With HER2 Expression in Biopsy and Resection Specimens HER2 expression - resection Missing	0 Participants	2 Participants

SECONDARY outcome

Timeframe: 3-6 months after surgery

The number of serious and non serious adverse events for both arms. Graded According to national Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 4.03.

Outcome measures

Measure	GM-CSF n=4 Participants Immunoadjuvant GM-CSF	NPS+GM-CSF n=9 Participants Vaccine with immunogenic peptide nelipepimut-S+GM-CSF (NPS+GM-CSF)
Number of Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 4.03 Serious Adverse Events	0 adverse events	2 adverse events
Number of Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 4.03 Non Serious Adverse Events	40 adverse events	91 adverse events

SECONDARY outcome

Timeframe: At resection

Presence of DCIS with Invasive Cancer.

Outcome measures

Measure	GM-CSF n=4 Participants Immunoadjuvant GM-CSF	NPS+GM-CSF n=9 Participants Vaccine with immunogenic peptide nelipepimut-S+GM-CSF (NPS+GM-CSF)
Number of Participants With Presence of Ductal Carcinoma in Situ (DCIS) Not Present	3 Participants	7 Participants
Number of Participants With Presence of Ductal Carcinoma in Situ (DCIS) Present	1 Participants	2 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: up to 6 months after completion of the vaccination series timepoint

Will utilize tissue-based cyclic immunofluorescence (t-CyCIF), a novel, highly multiplexed imaging modality that follows the imaging of formalin-fixed, paraffin embedded (FFPE) tissue sections at subcellular resolution across 20-60 distinct antigen channels. 4-6 panels that will be used include both my not be limited to an already optimized immune panel.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Up to 6 months after completion of the vaccination series timepoint

In the mastectomy samples only will perform core needle biopsies of the normal tissue, maximally distant from the tumor (ex vivo after the mastectomy if performed and store for future studies of immune infiltrates.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: up to 3 months after surgery

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Up to 6 months after completion of the vaccination series timepoint

We will define intra-tumoral TIL as those within the basement membrane. Stromal TIL will be defined as those in the periductal/lobular stroma including the intralobular stromal infiltrate. Cells in the interlobular stromal inflammatory infiltrate will be excluded. All mononuclear cells will be scored but polymorphonuclear leukocytes will be excluded. Intra-tumoral and stromal TILs will be scored as a continuous variable and the percentage of in the surgical specimen will be compared to that in the pre-vaccination diagnostic biopsy.

Outcome measures

Outcome data not reported

Adverse Events

GM-CSF

Serious events: 2 serious events

Other events: 4 other events

Deaths: 0 deaths

NPS+GM-CSF

Serious events: 0 serious events

Other events: 9 other events

Deaths: 0 deaths

Serious adverse events

Measure	GM-CSF n=4 participants at risk Immunoadjuvant GM-CSF	NPS+GM-CSF n=9 participants at risk Vaccine with immunogenic peptide nelipepimut-S+GM-CSF (NPS+GM-CSF)
Cardiac disorders Decreased Ejection Fraction	25.0% 1/4 • adverse events were assessed from randomization to the final follow up visit up to 8 months	0.00% 0/9 • adverse events were assessed from randomization to the final follow up visit up to 8 months
Infections and infestations Wound infection	25.0% 1/4 • adverse events were assessed from randomization to the final follow up visit up to 8 months	0.00% 0/9 • adverse events were assessed from randomization to the final follow up visit up to 8 months

Other adverse events

Measure	GM-CSF n=4 participants at risk Immunoadjuvant GM-CSF	NPS+GM-CSF n=9 participants at risk Vaccine with immunogenic peptide nelipepimut-S+GM-CSF (NPS+GM-CSF)
Gastrointestinal disorders Abdominal pain	0.00% 0/4 • adverse events were assessed from randomization to the final follow up visit up to 8 months	11.1% 1/9 • adverse events were assessed from randomization to the final follow up visit up to 8 months
Immune system disorders Allergic Reaction	0.00% 0/4 • adverse events were assessed from randomization to the final follow up visit up to 8 months	11.1% 1/9 • adverse events were assessed from randomization to the final follow up visit up to 8 months
Musculoskeletal and connective tissue disorders Arthralgia	0.00% 0/4 • adverse events were assessed from randomization to the final follow up visit up to 8 months	22.2% 2/9 • adverse events were assessed from randomization to the final follow up visit up to 8 months
Infections and infestations Breast Infection	0.00% 0/4 • adverse events were assessed from randomization to the final follow up visit up to 8 months	11.1% 1/9 • adverse events were assessed from randomization to the final follow up visit up to 8 months
Reproductive system and breast disorders Breast Pain	50.0% 2/4 • adverse events were assessed from randomization to the final follow up visit up to 8 months	33.3% 3/9 • adverse events were assessed from randomization to the final follow up visit up to 8 months
Injury, poisoning and procedural complications Bruising	25.0% 1/4 • adverse events were assessed from randomization to the final follow up visit up to 8 months	0.00% 0/9 • adverse events were assessed from randomization to the final follow up visit up to 8 months
Gastrointestinal disorders Constipation	25.0% 1/4 • adverse events were assessed from randomization to the final follow up visit up to 8 months	11.1% 1/9 • adverse events were assessed from randomization to the final follow up visit up to 8 months
Respiratory, thoracic and mediastinal disorders Cough	0.00% 0/4 • adverse events were assessed from randomization to the final follow up visit up to 8 months	22.2% 2/9 • adverse events were assessed from randomization to the final follow up visit up to 8 months
Injury, poisoning and procedural complications Dermatitis radiation	75.0% 3/4 • adverse events were assessed from randomization to the final follow up visit up to 8 months	44.4% 4/9 • adverse events were assessed from randomization to the final follow up visit up to 8 months
General disorders Erythema multiforme	0.00% 0/4 • adverse events were assessed from randomization to the final follow up visit up to 8 months	11.1% 1/9 • adverse events were assessed from randomization to the final follow up visit up to 8 months
General disorders Fatigue	0.00% 0/4 • adverse events were assessed from randomization to the final follow up visit up to 8 months	22.2% 2/9 • adverse events were assessed from randomization to the final follow up visit up to 8 months
General disorders Fever	0.00% 0/4 • adverse events were assessed from randomization to the final follow up visit up to 8 months	22.2% 2/9 • adverse events were assessed from randomization to the final follow up visit up to 8 months
General disorders Flu like symptoms	0.00% 0/4 • adverse events were assessed from randomization to the final follow up visit up to 8 months	11.1% 1/9 • adverse events were assessed from randomization to the final follow up visit up to 8 months
General disorders Headache	25.0% 1/4 • adverse events were assessed from randomization to the final follow up visit up to 8 months	11.1% 1/9 • adverse events were assessed from randomization to the final follow up visit up to 8 months
Vascular disorders Hot flashes	0.00% 0/4 • adverse events were assessed from randomization to the final follow up visit up to 8 months	11.1% 1/9 • adverse events were assessed from randomization to the final follow up visit up to 8 months
Vascular disorders Hypertension	0.00% 0/4 • adverse events were assessed from randomization to the final follow up visit up to 8 months	11.1% 1/9 • adverse events were assessed from randomization to the final follow up visit up to 8 months
General disorders Injection Site reaction	100.0% 4/4 • adverse events were assessed from randomization to the final follow up visit up to 8 months	100.0% 9/9 • adverse events were assessed from randomization to the final follow up visit up to 8 months
Musculoskeletal and connective tissue disorders Musculoskeletal and connective tissue disorder- other	0.00% 0/4 • adverse events were assessed from randomization to the final follow up visit up to 8 months	11.1% 1/9 • adverse events were assessed from randomization to the final follow up visit up to 8 months
Musculoskeletal and connective tissue disorders Myalgia	25.0% 1/4 • adverse events were assessed from randomization to the final follow up visit up to 8 months	22.2% 2/9 • adverse events were assessed from randomization to the final follow up visit up to 8 months
Respiratory, thoracic and mediastinal disorders Nasal Congestion	0.00% 0/4 • adverse events were assessed from randomization to the final follow up visit up to 8 months	11.1% 1/9 • adverse events were assessed from randomization to the final follow up visit up to 8 months
General disorders Pain	50.0% 2/4 • adverse events were assessed from randomization to the final follow up visit up to 8 months	11.1% 1/9 • adverse events were assessed from randomization to the final follow up visit up to 8 months
General disorders Pruritus	75.0% 3/4 • adverse events were assessed from randomization to the final follow up visit up to 8 months	33.3% 3/9 • adverse events were assessed from randomization to the final follow up visit up to 8 months
Surgical and medical procedures Seroma	0.00% 0/4 • adverse events were assessed from randomization to the final follow up visit up to 8 months	11.1% 1/9 • adverse events were assessed from randomization to the final follow up visit up to 8 months
Cardiac disorders Sinus Tachycardia	0.00% 0/4 • adverse events were assessed from randomization to the final follow up visit up to 8 months	11.1% 1/9 • adverse events were assessed from randomization to the final follow up visit up to 8 months
Infections and infestations Sinusitis	0.00% 0/4 • adverse events were assessed from randomization to the final follow up visit up to 8 months	22.2% 2/9 • adverse events were assessed from randomization to the final follow up visit up to 8 months
Skin and subcutaneous tissue disorders Mild Folliculitis	0.00% 0/4 • adverse events were assessed from randomization to the final follow up visit up to 8 months	11.1% 1/9 • adverse events were assessed from randomization to the final follow up visit up to 8 months
Skin and subcutaneous tissue disorders Skin Hyperpigmentation	50.0% 2/4 • adverse events were assessed from randomization to the final follow up visit up to 8 months	33.3% 3/9 • adverse events were assessed from randomization to the final follow up visit up to 8 months
Respiratory, thoracic and mediastinal disorders Sore Throat	0.00% 0/4 • adverse events were assessed from randomization to the final follow up visit up to 8 months	11.1% 1/9 • adverse events were assessed from randomization to the final follow up visit up to 8 months
Surgical and medical procedures Surgical and Medical Procedures Other	0.00% 0/4 • adverse events were assessed from randomization to the final follow up visit up to 8 months	22.2% 2/9 • adverse events were assessed from randomization to the final follow up visit up to 8 months
Infections and infestations Urinary Tract Infection	0.00% 0/4 • adverse events were assessed from randomization to the final follow up visit up to 8 months	11.1% 1/9 • adverse events were assessed from randomization to the final follow up visit up to 8 months
Reproductive system and breast disorders Vaginal Discharge	0.00% 0/4 • adverse events were assessed from randomization to the final follow up visit up to 8 months	11.1% 1/9 • adverse events were assessed from randomization to the final follow up visit up to 8 months

Additional Information

Dr. Isabelle Bedrosian, MD, Professor, Breast Surgical Oncology

UT MD Anderson Cancer Center

Phone: (713) 563-1872

Email: ibedrosian@mdanderson.org

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place

Restriction type: LTE60