Table 2.
Summary of Phase 2 and 3 Clinical Trials with Ipilimumab
| Phase/patient population | Design/schedule | Activity | Conclusions | Citation |
|---|---|---|---|---|
| Phase 2 (MDX10-08)/untreated advanced melanoma, n = 72 | Ipilimumab (3 mg/kg/month for 4 months) with or without DTIC (250 mg/m2 for 5 days monthly for 4 months) | Ipilimumab: DCR = 21.6%, durable disease control (≥24 weeks) in 2 patients, and OS 11.4 months | Ipilimumab resulted in clinically meaningful responses in advanced melanoma in combo. With DTIC. Combination was well tolerated; AEs were medically manageable | Hersh et al.17 |
| Ipilimumab/DTIC: DCR = 37.1%, durable disease control in 4 patients, and OS 14.3 months | ||||
| Phase 1/2 (CA184-022)/pretreated advanced melanoma, n = 217 | 0.3, 3, or 10 mg/kg Q3W for four doses then maintenance (Q12W) | 0.3 mg/kg: DCR = 13.7%, durable disease control 0%, and OS 8.6 months 3 mg/kg: DCR = 26.4%, durable disease control 3%, and OS 8.7 months 10 mg/kg: DCR = 29.2%, durable disease control 7%, and OS 11.4 months |
Ipilimumab had a dose-dependent effect on efficacy and safety, supporting further studies at a dose of 10 mg/kg | Wolchok et al.19 |
| Phase 2 (CA184-008)/pretreated advanced melanoma, n = 155 | 10 mg/kg ipilimumab Q3W for four doses then maintenance (Q12W) | BORR = 5.8%; DCR = 27.1%; 1-year survival rate = 47.2%; 2-year survival rate = 32.8%, median OS of 10.2 months | Ipilimumab has clinical activity with encouraging long-term survival | O'Day et al.18 |
| Phase 2 (CA184-007)/pretreated and treatment-naïve advanced melanoma, n = 115 | 10 mg/kg Q3W for four doses and randomized to receive prophylactic budesonide (arm A; n = 58) or placebo (arm B; n = 57) | Arm A: BORR = 12.1%, OS = 17.7 months Arm B: BORR = 15.8%, OS = 19.3 months |
Ipilimumab has activity with encouraging survival and manageable AEs | Weber et al.36 |
| Phase 2 (CA184-042)/melanoma with brain metastases, steroid-free (n = 51; arm A) or requiring steroids (n = 21; arm B) | 10 mg/kg Q3W for four doses; responding or stable patients could receive maintenance 10 mg/kg Q12W | Budesonide use did not affect the rate of grade 2 or higher diarrhea Arm A data at week 12: Global lesions (brain + non-CNS) = 4 PR, 5 SD Brain lesions only = 5 PR, 6 SD Response duration = 3–12 + months, SD duration = 1–7 months, median global PFS = 1.9 months |
Ipilimumab had similar activity in brain and non-CNS lesions | Lawrence et al.37 |
| Phase 3 (CA184-020)/patients with previously treated advanced melanoma, n = 676 | Randomized, double-blind study of 3 mg/kg Q3W × 4 ± gp100 vaccine, or vaccine only | Ipilimumab + gp100 (n = 403): CR = 1 (0.2%), PR = 22 (5.5%), SD = 58 (14.4%), BORR = 5.7%, median OS = 10.0 months, 1-year survival rate = 43.6%, 2-year survival rate = 21.6% | Ipilimumab with or without gp100 vaccine improved OS compared with vaccine alone; re-induction with ipilimumab at the time of disease progression can produce further clinical benefit | Hodi et al.38 |
| Ipilimumab only (n = 137): CR = 2 (1.5%), PR = 13 (9.5%), SD = 24 (17.5%), BORR = 10.9%, median OS = 10.1 months, 1-year survival rate = 45.6%, 2-year survival rate = 23.5% | ||||
| gp100 only (n = 136): CR = 0, PR = 2 (1.5%), SD = 13 (9.6%), BORR = 1.5%, median OS = 6.4 months, 1-year survival rate = 25.3%, 2-year survival rate = 13.7% | ||||
| Phase 2 (CA184-041)/chemo-naïve recurrent/metastatic NSCLC | Randomized, double-blind study of first-line ipilimumab (10 mg/kg Q3W) + CON P/C (175 mg/m2 AUC = 6 Q3W, (n = 70); or SEQ P/C (n = 68), or PBO, (n = 66); after P/C, ipilimumab maintenance therapy Q12W until toxicity or PD | SEQ regimen: Median PFS = 5.68 months versus 4.63 (PBO), p = 0.026 Median irPFS = 5.13 versus 4.21 (PBO), p = 0.024 No statistically significant differences in PFS for CON regimen or in OS for CON/SEQ (vs. PBO) |
Ipilimumab addition to P/C in a SEQ regimen extended PFS and irPFS in NSCLC patients compared with P/C alone | Lynch et al.39 |
DTIC, dacarbazine; DCR, disease control rate (CR + PR + SD/n); Q12W, every 12 weeks; BORR, best objective response rate; CNS, central nervous system; PFS, progression-free survival; NSCLC, nonsmall cell lung cancer; CON, consecutive; PBO, paclitaxel/carboplatin only; irPFS, immune-related progression-free survival; P/C, paclitaxel/carboplatin; PD, progressive disease.