Trial Outcomes & Findings for A Phase I/II Trial to Evaluate a Peptide Vaccine Plus Ipilimumab in Patients With Melanoma (NCT NCT02385669)

NCT ID: NCT02385669

Last Updated: 2020-05-05

Results Overview

Adverse event profile for the combination of ipilimumab and 6MHP

• Recruitment status: TERMINATED
• Study phase: PHASE1/PHASE2
• Target enrollment: 3 participants
• Primary outcome timeframe: 30 days after the last vaccination
• Results posted on: 2020-05-05

Participant Flow

Enrollment opened 4/29/15 Closed to enrollment December 2018. Enrollment has been slow due to changes in standard of care, especially the dominance of PD-1 blockade over CTLA-4 blockade. The study was closed to enrollment due to slow accrual, despite multiple revisions in the protocol to enhance enrollment.

Participant milestones

Measure	6MHP and Ipilimumab The vaccine drug product, 6MHP, consists of 6 class II MHC-restricted peptides derived from melanoma proteins. Each vaccine consists of 200 mcg of each of the six peptides. An aqueous solution of vaccine is mixed 1/1 with Montanide ISA-51 to form water-in-oil emulsions. Vaccines are administered days 1, 8, 15, 43, 64, and 85. All peptide vaccines are administered intradermally and subcutaneously. Ipilimumab will be administered in accord with the official prescribing information: 3 mg/kg intravenously once every 3 weeks, for 4 doses. Ipilimumab will be administered on days 1, 22, 43, and 64. Ipilimumab: Checkpoint blockade inhibitor 6MHP: 6 melanoma helper vaccine comprised of 6 class II MHC-restricted helper peptides
Overall Study STARTED	3
Overall Study COMPLETED	1
Overall Study NOT COMPLETED	2

Reasons for withdrawal

Measure

6MHP and Ipilimumab The vaccine drug product, 6MHP, consists of 6 class II MHC-restricted peptides derived from melanoma proteins. Each vaccine consists of 200 mcg of each of the six peptides. An aqueous solution of vaccine is mixed 1/1 with Montanide ISA-51 to form water-in-oil emulsions. Vaccines are administered days 1, 8, 15, 43, 64, and 85. All peptide vaccines are administered intradermally and subcutaneously. Ipilimumab will be administered in accord with the official prescribing information: 3 mg/kg intravenously once every 3 weeks, for 4 doses. Ipilimumab will be administered on days 1, 22, 43, and 64. Ipilimumab: Checkpoint blockade inhibitor 6MHP: 6 melanoma helper vaccine comprised of 6 class II MHC-restricted helper peptides

Overall Study Adverse Event

2

Baseline Characteristics

A Phase I/II Trial to Evaluate a Peptide Vaccine Plus Ipilimumab in Patients With Melanoma

Baseline characteristics by cohort

Measure	6MHP and Ipilimumab n=3 Participants The vaccine drug product, 6MHP, consists of 6 class II MHC-restricted peptides derived from melanoma proteins. Each vaccine consists of 200 mcg of each of the six peptides. An aqueous solution of vaccine is mixed 1/1 with Montanide ISA-51 to form water-in-oil emulsions. Vaccines are administered days 1, 8, 15, 43, 64, and 85. All peptide vaccines are administered intradermally and subcutaneously. Ipilimumab will be administered in accord with the official prescribing information: 3 mg/kg intravenously once every 3 weeks, for 4 doses. Ipilimumab will be administered on days 1, 22, 43, and 64. Ipilimumab: Checkpoint blockade inhibitor 6MHP: 6 melanoma helper vaccine comprised of 6 class II MHC-restricted helper peptides
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	2 Participants n=5 Participants
Age, Categorical >=65 years	1 Participants n=5 Participants
Age, Continuous	54 years n=5 Participants
Sex: Female, Male Female	1 Participants n=5 Participants
Sex: Female, Male Male	2 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	3 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants
Race (NIH/OMB) White	3 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Region of Enrollment United States	3 participants n=5 Participants

PRIMARY outcome

Timeframe: 30 days after the last vaccination

Population: All eligible enrolled and treated patients. Partiipants analyzed for any adverse event (AE) and for dose limiting toxicities (DLT).

Adverse event profile for the combination of ipilimumab and 6MHP

Outcome measures

Measure	6MHP and Ipilimumab n=3 Participants The vaccine drug product, 6MHP, consists of 6 class II MHC-restricted peptides derived from melanoma proteins. Each vaccine consists of 200 mcg of each of the six peptides. An aqueous solution of vaccine is mixed 1/1 with Montanide ISA-51 to form water-in-oil emulsions. Vaccines are administered days 1, 8, 15, 43, 64, and 85. All peptide vaccines are administered intradermally and subcutaneously. Ipilimumab will be administered in accord with the official prescribing information: 3 mg/kg intravenously once every 3 weeks, for 4 doses. Ipilimumab will be administered on days 1, 22, 43, and 64. Ipilimumab: Checkpoint blockade inhibitor 6MHP: 6 melanoma helper vaccine comprised of 6 class II MHC-restricted helper peptides
Safety (Adverse Event Profile) Number of participants with DLTs	2 Participants
Safety (Adverse Event Profile) Participants with any treatment-related AEs	3 Participants

PRIMARY outcome

Timeframe: through day 92

CD4+ T cell responses to the peptide vaccine, defined as:

1. any CD4+ T cell response to 6 melanoma helper peptides (6MHP) in peripheral blood mononuclear cells (PBMC) with a 10 fold (or greater) increase in response over background (high response) by ex vivo ELIspot assay.

2. CD4+ T cell high responses to 6MHP in PBMC at at least 2 consecutive time points having peripheral blood mononuclear cells (PBMC) with a 10 fold (or greater) increase in response over background by ex vivo ELIspot assay.

3. CD4+ T cell high response to 6MHP in sentinel immunized lymph node (SIN).

Outcome measures

Measure	6MHP and Ipilimumab n=3 Participants The vaccine drug product, 6MHP, consists of 6 class II MHC-restricted peptides derived from melanoma proteins. Each vaccine consists of 200 mcg of each of the six peptides. An aqueous solution of vaccine is mixed 1/1 with Montanide ISA-51 to form water-in-oil emulsions. Vaccines are administered days 1, 8, 15, 43, 64, and 85. All peptide vaccines are administered intradermally and subcutaneously. Ipilimumab will be administered in accord with the official prescribing information: 3 mg/kg intravenously once every 3 weeks, for 4 doses. Ipilimumab will be administered on days 1, 22, 43, and 64. Ipilimumab: Checkpoint blockade inhibitor 6MHP: 6 melanoma helper vaccine comprised of 6 class II MHC-restricted helper peptides
CD4+ T Cell Responses in the Blood and in the Sentinel Immunized Node Number with T cell response to 6MHP in PBMC	2 Participants
CD4+ T Cell Responses in the Blood and in the Sentinel Immunized Node Number with T cell response at 2 consecutive times	0 Participants
CD4+ T Cell Responses in the Blood and in the Sentinel Immunized Node T cell reactivity to 6MHP in SIN	1 Participants

SECONDARY outcome

Timeframe: through day 92

An evaluation of epitope-spreading for CD8+ T cells in the blood and the sentinel immunized node that are reactive to a panel of defined melanoma antigens.

Outcome measures

Outcome data not reported

Adverse Events

6MHP and Ipilimumab

Serious events: 1 serious events

Other events: 3 other events

Deaths: 0 deaths

Serious adverse events

Measure

6MHP and Ipilimumab n=3 participants at risk The vaccine drug product, 6MHP, consists of 6 class II MHC-restricted peptides derived from melanoma proteins. Each vaccine consists of 200 mcg of each of the six peptides. An aqueous solution of vaccine is mixed 1/1 with Montanide ISA-51 to form water-in-oil emulsions. Vaccines are administered days 1, 8, 15, 43, 64, and 85. All peptide vaccines are administered intradermally and subcutaneously. Ipilimumab will be administered in accord with the official prescribing information: 3 mg/kg intravenously once every 3 weeks, for 4 doses. Ipilimumab will be administered on days 1, 22, 43, and 64. Ipilimumab: Checkpoint blockade inhibitor 6MHP: 6 melanoma helper vaccine comprised of 6 class II MHC-restricted helper peptides

Eye disorders uveitis

33.3% 1/3 • Number of events 1 • 3 months

Other adverse events

Measure	6MHP and Ipilimumab n=3 participants at risk The vaccine drug product, 6MHP, consists of 6 class II MHC-restricted peptides derived from melanoma proteins. Each vaccine consists of 200 mcg of each of the six peptides. An aqueous solution of vaccine is mixed 1/1 with Montanide ISA-51 to form water-in-oil emulsions. Vaccines are administered days 1, 8, 15, 43, 64, and 85. All peptide vaccines are administered intradermally and subcutaneously. Ipilimumab will be administered in accord with the official prescribing information: 3 mg/kg intravenously once every 3 weeks, for 4 doses. Ipilimumab will be administered on days 1, 22, 43, and 64. Ipilimumab: Checkpoint blockade inhibitor 6MHP: 6 melanoma helper vaccine comprised of 6 class II MHC-restricted helper peptides
Endocrine disorders adrenal insufficiency	33.3% 1/3 • Number of events 1 • 3 months
Eye disorders blurred vision	33.3% 1/3 • 3 months
Eye disorders Other	33.3% 1/3 • 3 months
Gastrointestinal disorders Diarrhea	33.3% 1/3 • 3 months
Gastrointestinal disorders Nausea	66.7% 2/3 • 3 months
Gastrointestinal disorders Vomiting	66.7% 2/3 • 3 months
General disorders Chills	33.3% 1/3 • 3 months
General disorders Edema limbs	33.3% 1/3 • 3 months
General disorders Fatigue	66.7% 2/3 • 3 months
General disorders Fever	33.3% 1/3 • 3 months
General disorders Flu like symptoms	33.3% 1/3 • 3 months
General disorders Injection site reaction	66.7% 2/3 • 3 months
Investigations alanine aminotransferase increased	33.3% 1/3 • 3 months
Investigations aspartate aminotransferase increased	33.3% 1/3 • 3 months
Investigations weight loss	33.3% 1/3 • 3 months
Metabolism and nutrition disorders anorexia	33.3% 1/3 • 3 months
Metabolism and nutrition disorders dehydration	33.3% 1/3 • 3 months
Musculoskeletal and connective tissue disorders myalgia	33.3% 1/3 • 3 months
Nervous system disorders headache	33.3% 1/3 • 3 months
Skin and subcutaneous tissue disorders Pruritis	66.7% 2/3 • 3 months
Skin and subcutaneous tissue disorders skin hypopigmentation	66.7% 2/3 • 3 months
Skin and subcutaneous tissue disorders skin induration	100.0% 3/3 • 3 months
Skin and subcutaneous tissue disorders skin ulceration	33.3% 1/3 • 3 months

Additional Information

Craig L. Slingluff, Jr. MD

University of Virginia

Phone: 434-924-9311

Email: cls8h@virginia.edu

Results disclosure agreements

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