Table 1.

Summary of Phase 1 Clinical Trials with Ipilimumab

Patient population	Design/schedule	Activity	Conclusions	Citation
Untreated advanced melanoma, n = 36	Ipilimumab 0.1–3 mg/kg plus IL-2 720,000 IU/kg	Responses in 8/36 patients (22%); durations of 11–19 months	No synergistic effect in combination; antitumor effects of ipilimumab result from T-cell activation	Maker et al.26,27
Prostate cancer, colon cancer, and NHL, n = 11 (after no response to tumor-specific vaccination)	Ipilimumab 3 mg/kg induction then 1.5 mg/kg maintenance monthly for four cycles	Tumor regression in 2/4 patients with lymphoma	Evidence of activity and well tolerated; reduction in Tregs noted	O'Mahony et al.28
Advanced melanoma and ovarian cancer, n = 9	Single dose—3 mg/kg (patients previously vaccinated—GVAX)	Activity and extensive tumor necrosis with lymphocyte and granulocyte infiltration in 3 melanoma patients; reduced/stabilized CA-125 in 2 ovarian cancer patients	No serious toxicities and evidence of increased tumor immunity	Hodi et al.29
Advanced melanoma, n = 11; ovarian cancer, n = 9	Single dose—3 mg/kg (retreatment permitted after 2/3 months)—following GVAX	Antitumor effect in 8/11 melanoma patients (including 3 PRs); 4/9 ovarian cancer patients had SD	Ipilimumab following GVAX gives clinically meaningful antitumor immunity without grade 3 or 4 toxicity in most melanoma patients	Hodi et al.30
Advanced melanoma, n = 14	Ipilimumab 3 mg/kg Q3W plus peptide vaccine	Two CRs and 1 PR	Immune-related AEs and antitumor activity suggests a role for CTLA-4 in breaking tolerance to cancer antigens	Phan et al.31
CRPC, n = 14 (including pretreated patients)	Single dose—3 mg/kg	PSA decrease of ≥50% in 2/14 patients	Single 3 mg/kg dose is safe; no significant autoimmunity	Small et al.25
Untreated CRPC, n = 24	Dose escalation: ipilimumab 0.5–3 mg/kg plus GM-CSF 250 μg/m2/day	3/6 patients on highest dose had PSA declines >50%	Evidence of activity and 3 mg/kg associated with more frequent expansion of circulating activated cytotoxic T cells than lower doses	Fong et al.32
Metastatic CRPC n = 36	GM-CSF 250 μg/m2/day (days 1–14 of 28-day cycle) + ipilimumab at escalating doses (0.5–10 mg/kg) on day 1 of each cycle × 6	3/6 patients treated with ipilimumab 3 mg/kg had confirmed PSA decline ≥50% and TTP 22, 26, and 103 weeks; 1 patient had PR in hepatic metastases; 1 patient on 10 mg/kg ipilimumab had PSA decline ≥50% and TTP 39 weeks	Ipilimumab combined with GM-CSF induced clinical responses in CRPC with the highest response proportion at the 3 mg/kg dose level	Harzstark et al.33
Metastatic CRPC n = 30	PSA vaccine days 1, 15, and 29, then monthly + ipilimumab 1, 3, 5, or 10 mg/kg in SEQ dose levels monthly; after 6 months patients could receive maintenance ipilimumab Q3M	Median OS (all patients) 31.8 months, with 74% survival probability at 24 months; median OS for chemotherapy naïve subset 30.9 months OS was dose independent	Based on historical data for the same vaccine (OS ∼26 months), addition of ipilimumab may augment the clinical benefit of vaccines in CRPC	Madan et al.34
Relapsed/refractory B-cell NHL n = 18	Ipilimumab 3 mg/kg, then monthly at 1 mg/kg × 3 (dose level 1), then escalation to 3 mg/kg monthly × 4	1 patient with diffuse large B-cell lymphoma had CR (>31 months), 1 patient with follicular lymphoma had PR (>19 months)	Ipilimumab has antitumor activity in patients with B-cell lymphoma	Ansell et al.35

IL-2, interleukin-2; GVAX, irradiated, autologous tumor cells engineered to secrete granulocyte macrophage colony-stimulating factor; PR, partial response; SD, stable disease; Q3W, every 3 weeks; CR, complete response; AEs, adverse events; CTLA-4, cytotoxic T lymphocyte antigen-4; CRPC, castrate-resistant prostate cancer; PSA, prostate-specific antigen; GM-CSF, granulocyte macrophage colony-stimulating factor; TTP, time to progression; OS, overall survival; SEQ, sequential; Q3M, every 3 months; NHL, non-Hodgkin's lymphoma.