Trial Outcomes & Findings for Phase I Study of Intralesional Bacillus Calmette-Guerin (BCG) Followed by Ipilimumab in Advanced Metastatic Melanoma (NCT NCT01838200)

Last Updated: 2022-10-12

Results Overview

Toxicity was graded in accordance with the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 4.0. Treatment-emergent adverse events (TEAEs) were reported based on clinical laboratory tests, physical examinations, and vital signs from pre-treatment through the study period. Dose-limiting toxicity (DLT) for BCG was defined as any ≥ Grade 3 local injection site reaction (ulceration or necrosis requiring operative intervention), and DLT for ipilimumab was defined as any toxicity that required dosing modifications in accordance with the recommendations in the local product labelling, or any ≥ Grade 3 hematologic or nonhematologic toxicity that was definitely, probably, or possibly related to the administration of ipilimumab.

Recruitment status

TERMINATED

Study phase

PHASE1

Target enrollment

5 participants

Primary outcome timeframe

Continuously for up to 5 months

Results posted on

2022-10-12

Participant Flow

The study was terminated early due to slow enrollment; thus, Cohort 1 Group 3 and Cohort 2 were not enrolled.

Participant milestones

Participant milestones
Measure	Cohort 1, Group 1 (BCG 0.16-0.64 × 10^6 CFU) Patients with an induration \<10 mm in diameter after the baseline PPD reactivity test received BCG (IL, 200 µL volume) at a dose of 0.16 - 0.64 × 10\^6 CFU on Day 1. Isoniazid (300 mg) was administered orally every day from Days 29 through 56. Ipilimumab (3 mg/kg) was administered as a 90-minute IV infusion every 3 weeks (± 3 days) on Days 36, 57, 78, and 99.	Cohort 1, Group 2 (BCG 0.8-3.2 × 10^6 CFU) Patients with an induration \<10 mm in diameter after the baseline PPD reactivity test received BCG (IL, 200 µL volume) at a dose of 0.8 - 3.2 × 10\^6 CFU on Day 1. Isoniazid (300 mg) was administered orally every day from Days 29 through 56. Ipilimumab (3 mg/kg) was administered as a 90-minute IV infusion every 3 weeks (± 3 days) on Days 36, 57, 78, and 99.
Overall Study STARTED	3	2
Overall Study COMPLETED	0	0
Overall Study NOT COMPLETED	3	2

Reasons for withdrawal

Reasons for withdrawal
Measure	Cohort 1, Group 1 (BCG 0.16-0.64 × 10^6 CFU) Patients with an induration \<10 mm in diameter after the baseline PPD reactivity test received BCG (IL, 200 µL volume) at a dose of 0.16 - 0.64 × 10\^6 CFU on Day 1. Isoniazid (300 mg) was administered orally every day from Days 29 through 56. Ipilimumab (3 mg/kg) was administered as a 90-minute IV infusion every 3 weeks (± 3 days) on Days 36, 57, 78, and 99.	Cohort 1, Group 2 (BCG 0.8-3.2 × 10^6 CFU) Patients with an induration \<10 mm in diameter after the baseline PPD reactivity test received BCG (IL, 200 µL volume) at a dose of 0.8 - 3.2 × 10\^6 CFU on Day 1. Isoniazid (300 mg) was administered orally every day from Days 29 through 56. Ipilimumab (3 mg/kg) was administered as a 90-minute IV infusion every 3 weeks (± 3 days) on Days 36, 57, 78, and 99.
Overall Study Adverse Event	0	2
Overall Study Progressive disease	3	0

Baseline Characteristics

Phase I Study of Intralesional Bacillus Calmette-Guerin (BCG) Followed by Ipilimumab in Advanced Metastatic Melanoma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Cohort 1, Group 1 (BCG 0.16-0.64 × 10^6 CFU) n=3 Participants Patients with an induration \<10 mm in diameter after the baseline PPD reactivity test received BCG (IL, 200 µL volume) at a dose of 0.16 - 0.64 × 10\^6 CFU on Day 1. Isoniazid (300 mg) was administered orally every day from Days 29 through 56. Ipilimumab (3 mg/kg) was administered as a 90-minute IV infusion every 3 weeks (± 3 days) on Days 36, 57, 78, and 99.	Cohort 1, Group 2 (BCG 0.8-3.2 × 10^6 CFU) n=2 Participants Patients with an induration \<10 mm in diameter after the baseline PPD reactivity test received BCG (IL, 200 µL volume) at a dose of 0.8 - 3.2 × 10\^6 CFU on Day 1. Isoniazid (300 mg) was administered orally every day from Days 29 through 56. Ipilimumab (3 mg/kg) was administered as a 90-minute IV infusion every 3 weeks (± 3 days) on Days 36, 57, 78, and 99.	Total n=5 Participants Total of all reporting groups
Age, Continuous	61.3 years n=5 Participants	53.5 years n=7 Participants	58.2 years n=5 Participants
Sex: Female, Male Female	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Sex: Female, Male Male	2 Participants n=5 Participants	1 Participants n=7 Participants	3 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	3 Participants n=5 Participants	2 Participants n=7 Participants	5 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 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	3 Participants n=5 Participants	2 Participants n=7 Participants	5 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	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment Australia	3 Participants n=5 Participants	2 Participants n=7 Participants	5 Participants n=5 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) at Baseline 0	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) at Baseline 1	1 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants

PRIMARY outcome

Timeframe: Continuously for up to 5 months

Population: The Safety Analysis Set includes all patients who received at least 1 dose of study treatment.

Outcome measures

Outcome measures
Measure	Cohort 1, Group 1 (BCG 0.16-0.64 × 10^6 CFU) n=3 Participants Patients with an induration \<10 mm in diameter after the baseline PPD reactivity test received BCG (IL, 200 µL volume) at a dose of 0.16 - 0.64 × 10\^6 CFU on Day 1. Isoniazid (300 mg) was administered orally every day from Days 29 through 56. Ipilimumab (3 mg/kg) was administered as a 90-minute IV infusion every 3 weeks (± 3 days) on Days 36, 57, 78, and 99.	Cohort 1, Group 2 (BCG 0.8-3.2 × 10^6 CFU) n=2 Participants Patients with an induration \<10 mm in diameter after the baseline PPD reactivity test received BCG (IL, 200 µL volume) at a dose of 0.8 - 3.2 × 10\^6 CFU on Day 1. Isoniazid (300 mg) was administered orally every day from Days 29 through 56. Ipilimumab (3 mg/kg) was administered as a 90-minute IV infusion every 3 weeks (± 3 days) on Days 36, 57, 78, and 99.
Number of Patients With Treatment-emergent Adverse Events Maximum grade 1 TEAE	0 Participants	0 Participants
Number of Patients With Treatment-emergent Adverse Events Maximum grade 2 TEAE	1 Participants	0 Participants
Number of Patients With Treatment-emergent Adverse Events Maximum grade 3 TEAE	2 Participants	1 Participants
Number of Patients With Treatment-emergent Adverse Events BCG-related TEAE	0 Participants	1 Participants
Number of Patients With Treatment-emergent Adverse Events Ipilimumab-related TEAE	1 Participants	2 Participants
Number of Patients With Treatment-emergent Adverse Events Isoniazid-related TEAE	0 Participants	0 Participants
Number of Patients With Treatment-emergent Adverse Events Serious TEAE	2 Participants	1 Participants
Number of Patients With Treatment-emergent Adverse Events TEAE Leading to BCG Discontinuation	0 Participants	0 Participants
Number of Patients With Treatment-emergent Adverse Events TEAE Leading to Ipilimumab Discontinuation	1 Participants	2 Participants
Number of Patients With Treatment-emergent Adverse Events TEAE Leading to Isoniazid Discontinuation	0 Participants	0 Participants
Number of Patients With Treatment-emergent Adverse Events TEAE Meeting DLT Criteria	0 Participants	2 Participants
Number of Patients With Treatment-emergent Adverse Events Any TEAE	3 Participants	2 Participants
Number of Patients With Treatment-emergent Adverse Events Maximum grade 4 TEAE	0 Participants	1 Participants

SECONDARY outcome

Timeframe: Up to 5 months

Population: The Efficacy Analysis Set includes all patients who received at least 1 dose of study treatment and had response evaluated through Week 17.

Tumor responses were evaluated using computed tomography and clinical photography at Baseline, Weeks 6, 17, 21, and 30 (± 3-day window for each assessment), and at the end of the study. Tumor response was designated according to the Response Evaluation Criteria in Solid Tumors (RECIST) (version 1.1). Per RECIST, target lesions are categorized as follows: Complete Response (CR): Disappearance of all target lesions (no evaluable disease); Partial Response (PR): ≥ 30% decrease in the sum of the longest diameter of target lesions; Progressive Disease (PD): ≥ 20% increase in the sum of the longest diameter of target lesions; Stable Disease (SD): small changes that do not meet above criteria.

Outcome measures

Outcome measures
Measure	Cohort 1, Group 1 (BCG 0.16-0.64 × 10^6 CFU) n=3 Participants Patients with an induration \<10 mm in diameter after the baseline PPD reactivity test received BCG (IL, 200 µL volume) at a dose of 0.16 - 0.64 × 10\^6 CFU on Day 1. Isoniazid (300 mg) was administered orally every day from Days 29 through 56. Ipilimumab (3 mg/kg) was administered as a 90-minute IV infusion every 3 weeks (± 3 days) on Days 36, 57, 78, and 99.	Cohort 1, Group 2 (BCG 0.8-3.2 × 10^6 CFU) n=2 Participants Patients with an induration \<10 mm in diameter after the baseline PPD reactivity test received BCG (IL, 200 µL volume) at a dose of 0.8 - 3.2 × 10\^6 CFU on Day 1. Isoniazid (300 mg) was administered orally every day from Days 29 through 56. Ipilimumab (3 mg/kg) was administered as a 90-minute IV infusion every 3 weeks (± 3 days) on Days 36, 57, 78, and 99.
Number of Patients With Best Overall Clinical Tumor Response Best response: SD	2 Participants	0 Participants
Number of Patients With Best Overall Clinical Tumor Response Best response: PD	1 Participants	2 Participants

SECONDARY outcome

Timeframe: Up to 5 months

Population: The Efficacy Analysis Set includes all patients who received at least 1 dose of study treatment and had response evaluated through Week 17.

Immune-related tumor responses were evaluated using computed tomography and clinical photography at Baseline, Weeks 6, 17, 21, and 30 (± 3-day window for each assessment), and at the end of the study. Tumor response was designated according to the immune-related Response Criteria (irRC) (Wolchok et al. Clin Cancer Res 2009;15:7412-20) into the following categories: immune-related complete response (irCR) requires disappearance of all lesions in two consecutive observations not less than 4 weeks apart; immune-related partial response (irPR) requires ≥ 50% decrease in tumor burden compared with baseline in two observations at least 4 weeks apart; immune-related stable disease (irSD) is assigned when neither a 50% decrease from baseline tumor burden nor a 25% increase in tumor burden from nadir can be established; immune-related progressive disease (irPD) requires a ≥ 25% increase from nadir in tumor burden at any single time point in two consecutive observations at least 4 weeks apart.

Outcome measures

Outcome measures
Measure	Cohort 1, Group 1 (BCG 0.16-0.64 × 10^6 CFU) n=3 Participants Patients with an induration \<10 mm in diameter after the baseline PPD reactivity test received BCG (IL, 200 µL volume) at a dose of 0.16 - 0.64 × 10\^6 CFU on Day 1. Isoniazid (300 mg) was administered orally every day from Days 29 through 56. Ipilimumab (3 mg/kg) was administered as a 90-minute IV infusion every 3 weeks (± 3 days) on Days 36, 57, 78, and 99.	Cohort 1, Group 2 (BCG 0.8-3.2 × 10^6 CFU) n=2 Participants Patients with an induration \<10 mm in diameter after the baseline PPD reactivity test received BCG (IL, 200 µL volume) at a dose of 0.8 - 3.2 × 10\^6 CFU on Day 1. Isoniazid (300 mg) was administered orally every day from Days 29 through 56. Ipilimumab (3 mg/kg) was administered as a 90-minute IV infusion every 3 weeks (± 3 days) on Days 36, 57, 78, and 99.
Number of Patients With Best Overall Immune-related Tumor Response Best response: irSD	1 Participants	1 Participants
Number of Patients With Best Overall Immune-related Tumor Response Best response: irPD	2 Participants	0 Participants
Number of Patients With Best Overall Immune-related Tumor Response Not evaluable by irRC	0 Participants	1 Participants

Adverse Events

Cohort 1, Group 1 (BCG 0.16-0.64 × 10^6 CFU)

Serious events: 2 serious events

Other events: 3 other events

Deaths: 0 deaths

Cohort 1, Group 2 (BCG 0.8-3.2 × 10^6 CFU)

Serious events: 1 serious events

Other events: 2 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Cohort 1, Group 1 (BCG 0.16-0.64 × 10^6 CFU) n=3 participants at risk Patients with an induration \<10 mm in diameter after the baseline PPD reactivity test received BCG (IL, 200 µL volume) at a dose of 0.16 - 0.64 × 10\^6 CFU on Day 1. Isoniazid (300 mg) was administered orally every day from Days 29 through 56. Ipilimumab (3 mg/kg) was administered as a 90-minute IV infusion every 3 weeks (± 3 days) on Days 36, 57, 78, and 99.	Cohort 1, Group 2 (BCG 0.8-3.2 × 10^6 CFU) n=2 participants at risk Patients with an induration \<10 mm in diameter after the baseline PPD reactivity test received BCG (IL, 200 µL volume) at a dose of 0.8 - 3.2 × 10\^6 CFU on Day 1. Isoniazid (300 mg) was administered orally every day from Days 29 through 56. Ipilimumab (3 mg/kg) was administered as a 90-minute IV infusion every 3 weeks (± 3 days) on Days 36, 57, 78, and 99.
Gastrointestinal disorders Colitis	0.00% 0/3 • All adverse events (AEs) occurring between the signing of informed consent and the off-study date were documented, regardless of the causal relationship to study drug. AEs occurring after the first dose of study drug were considered treatment emergent (i.e., TEAEs) and are presented in the summary tabulations. The AE reporting period for this study was up to 5 months. AE documentation included onset/resolution dates, severity using the NCI CTCAE (version 4.0), seriousness, relationship to study drug, study drug action taken, treatment, and outcome. In summaries, treatment-related AEs included those with a "possible", "probable", or "definite" relationship to study drug; preferred terms were counted only once per patient at the maximum reported grade.	50.0% 1/2 • All adverse events (AEs) occurring between the signing of informed consent and the off-study date were documented, regardless of the causal relationship to study drug. AEs occurring after the first dose of study drug were considered treatment emergent (i.e., TEAEs) and are presented in the summary tabulations. The AE reporting period for this study was up to 5 months. AE documentation included onset/resolution dates, severity using the NCI CTCAE (version 4.0), seriousness, relationship to study drug, study drug action taken, treatment, and outcome. In summaries, treatment-related AEs included those with a "possible", "probable", or "definite" relationship to study drug; preferred terms were counted only once per patient at the maximum reported grade.
Respiratory, thoracic and mediastinal disorders Pleural effusion	33.3% 1/3 • All adverse events (AEs) occurring between the signing of informed consent and the off-study date were documented, regardless of the causal relationship to study drug. AEs occurring after the first dose of study drug were considered treatment emergent (i.e., TEAEs) and are presented in the summary tabulations. The AE reporting period for this study was up to 5 months. AE documentation included onset/resolution dates, severity using the NCI CTCAE (version 4.0), seriousness, relationship to study drug, study drug action taken, treatment, and outcome. In summaries, treatment-related AEs included those with a "possible", "probable", or "definite" relationship to study drug; preferred terms were counted only once per patient at the maximum reported grade.	0.00% 0/2 • All adverse events (AEs) occurring between the signing of informed consent and the off-study date were documented, regardless of the causal relationship to study drug. AEs occurring after the first dose of study drug were considered treatment emergent (i.e., TEAEs) and are presented in the summary tabulations. The AE reporting period for this study was up to 5 months. AE documentation included onset/resolution dates, severity using the NCI CTCAE (version 4.0), seriousness, relationship to study drug, study drug action taken, treatment, and outcome. In summaries, treatment-related AEs included those with a "possible", "probable", or "definite" relationship to study drug; preferred terms were counted only once per patient at the maximum reported grade.
Blood and lymphatic system disorders Lymph node pain	33.3% 1/3 • All adverse events (AEs) occurring between the signing of informed consent and the off-study date were documented, regardless of the causal relationship to study drug. AEs occurring after the first dose of study drug were considered treatment emergent (i.e., TEAEs) and are presented in the summary tabulations. The AE reporting period for this study was up to 5 months. AE documentation included onset/resolution dates, severity using the NCI CTCAE (version 4.0), seriousness, relationship to study drug, study drug action taken, treatment, and outcome. In summaries, treatment-related AEs included those with a "possible", "probable", or "definite" relationship to study drug; preferred terms were counted only once per patient at the maximum reported grade.	0.00% 0/2 • All adverse events (AEs) occurring between the signing of informed consent and the off-study date were documented, regardless of the causal relationship to study drug. AEs occurring after the first dose of study drug were considered treatment emergent (i.e., TEAEs) and are presented in the summary tabulations. The AE reporting period for this study was up to 5 months. AE documentation included onset/resolution dates, severity using the NCI CTCAE (version 4.0), seriousness, relationship to study drug, study drug action taken, treatment, and outcome. In summaries, treatment-related AEs included those with a "possible", "probable", or "definite" relationship to study drug; preferred terms were counted only once per patient at the maximum reported grade.

Other adverse events

Additional Information

Jonathan Skipper PhD

Ludwig Institute for Cancer Research

Phone: (212) 450-1539

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60