Table 1.
Summary of phase 1/2 data for ipilimumab in CRPC
| Study/phase | Population (n)1 | Regimen | Dose/schedule | Endpoints | Efficacy results3 | Safety results3 | Reference(s) |
|---|---|---|---|---|---|---|---|
| CA184-0172 NCT00323882 (Phase 2) | Metastatic CRPC, pre- and postdocetaxel (70) | Monotherapy or with one prior dose of XRT | 3, 5, or 10 mg/kg monotherapy, 3 or 10 mg/kg with prior XRT, q3w × 4 | Primary: safety Secondary: PSA responses, metabolic bone activity | 21% (15 pts) had PSA responses (15.4% in chemo-naïve; 9.5% in chemo-pretreated) | 11 pts with 13 grade ≥3 irAEs; no DLTs observed, no MTD or DLT | Slovin et al. 26 |
| CA184-0192 NCT00050596 (Phase 2) | HRPC, docetaxel eligible (43) | Monotherapy or with docetaxel | 3 mg/kg, monthly × 4 | Safety and activity between arms | Two pts who received ipilimumab monotherapy and one pt who received ipilimumab + docetaxel had confirmed PSA responses | 18 pts experienced 52 SAEs, 10 of which were attributed to ipilimumab | Small et al. 27 |
| CA184-0092 (Phase 1) | Advanced HRPC; pre- and postchemo (14) | Monotherapy | 3 mg/kg, one dose (two retreated at progression) | Safety, PK, PSA, objective responses (per reference at right) | Two pts had PSA declines of ≥50% | One pt experienced grade 3 rash/pruritus | Small et al. 25 |
| CA184-118 NCT00170157 (Phase 2) | Advanced chemo-naïve CRPC (108) | With AA versus AA alone | 3 mg/kg, one dose | Primary: percent without progression at 18 months Secondary: PSA responses | 55% versus 38% undetectable PSA by 3 months | In combination arm, grade ≥3 irAEs included colitis (4.5%) and diarrhea (4.5%) | Tollefson et al. 28 |
| CA184-098 NCT00064129 (Phase 1/2) | Metastatic CRPC, docetaxel eligible (24) (36) | With GM-CSF | Phase 1: 0.5, 1.5, 3, 5, or 10 mg/kg, monthly; expansion: 3 mg/kg monthly × 6 | Primary for phase 1: MTD and safety; primary for expansion: PSA response Secondary for phase 1: T-cell immunity/response, PK, PSA response, ORR; secondary for expansion: percent activated naïve/memory T cells, epitopes for prostate antigens, T-cell response in HLA+ pts, safety, PSA response, ORR | At 3 mg/kg, 50% (three pts) had PSA declines of ≥50%, 1 PR; at 10 mg/kg, 17% (one pt) had PSA declines of ≥50% | irAEs correlated with dose (≥3 mg/kg) and PSA response | Small et al. 29; Fong et al. 30; Harzstark et al. 31 |
| CA184-119 (Phase 1) | Metastatic chemo-naïve HRPC (12 escalation, 16 expansion) | With GVAX | 0.3, 1, 3, or 5 mg/kg, monthly; expansion = 3 mg/kg | Primary: safety, MTD Secondary: TTP, PSA response, immune response, reduction in metabolic bone activity, survival | Six pts (five in escalation, one in expansion) receiving ≥3 mg/kg had PSA declines of ≥50% | Escalation cohort: five pts who received 3 or 5 mg/kg had grade ≥2 irAEs (four had hypophysitis, one had sarcoid alveolitis [DLT]; expansion cohort: two pts had grade 2 hypophysitis, three pts had grade 1 or 2 colitis, and one pt had grade 3 hepatitis | van den Eertwegh et al. 32 |
| CA184-100 NCT00124670 (Phase 1) | Metastatic CRPC, chemo-naïve (24) and postdocetaxel (6) | With PSA-Tricom/PROSTVAC + GM-CSF | 1, 3, 5, or 10 mg/kg, monthly × 6 | Primary: MTD of regimen, safety Secondary: PSA and RECIST responses in HLA-A2+ pts; immunologic response (increase in PSA-specific T cells | 15 pts had PSA declines (14 chemo-naïve, one pt postdocetaxel, all 3, 5, or 10 mg/kg), six were ≥50%; median PFS in chemo-naïve and postdocetaxel pts was 5.9 and 2.4 months; 3/12 unconfirmed PRs; median OS 34.4 months; 2-year OS 73% | No DLTs; most common AE was grade 1/2 site reaction; 8 (0/3, 2/6, 2/6 and 4/15 events in 1, 3, 5, or 10 mg/kg cohorts, respectively) grade ≥3 irAEs: 3 endocrinopathies, 2 rash, 1 diarrhea, 1 neutropenia, 1 elevated liver enzymes | Mohebtash et al. 33; Mohebtash et al. 34; Madan et al. 35 |
AA, androgen ablation; AE, adverse event; chemo, chemotherapy; CRPC, castration-resistant prostate cancer; DLT, dose-limiting toxicity; GM-CSF, granulocyte macrophage colony-stimulating growth factor; HLA, human leukocyte antigen; HRPC, hormone-refractory prostate cancer; irAEs, immune-related adverse events; MTD, maximum-tolerated dose; ORR, overall response rate; OS, overall survival; PFS, progression-free survival; PK, pharmacokinetics; PR, partial response; PSA, prostate-specific antigen; pt, patient; qXw, every X weeks; SAEs, serious (grade ≥3) adverse events; TTP, time to progression; XRT, radiotherapy.
1
Population descriptors are listed as defined in publication of data.
2
Trial sponsored by Bristol-Myers Squibb.
3
Results as reported in publicly available materials; most recent publicly available reports may be of interim data.