GEN501
Targeting CD38 with Daratumumab Monotherapy in Multiple Myeloma (GEN501)
Phase 1/2NCT00574288
- Population
- Relapsed myeloma, or relapsed myeloma refractory to two or more prior lines; part 2 median of four prior treatments, 76% with prior autologous stem-cell transplant.
- Design
- Phase 1-2 open-label dose-escalation (part 1) and dose-expansion (part 2) study of single-agent daratumumab; part 2 gave 8 or 16 mg per kg once weekly (8 doses), twice monthly (8 doses) and then monthly for up to 24 months. The registry lists 104 enrolled; the abstract reports part 2 cohorts of 30 and 42 patients. The abstract names safety, efficacy and pharmacokinetics as end points and does not designate a single primary end point.
- Arms
- Daratumumab 8 mg/kg (part 2 cohort) (experimental, n = 30): Daratumumab 8 mg per kg of body weight
- Daratumumab 16 mg/kg (part 2 cohort) (experimental, n = 42): Daratumumab 16 mg per kg of body weight
- People
- Lokhorst HM
Show the numbers
| Endpoint | Analysis | Daratumumab 8 mg/kg (part 2 cohort) / Daratumumab 16 mg/kg (part 2 cohort) | Control | Effect |
|---|---|---|---|---|
| ORRPart 2 expansion cohorts | primaryLokhorst 2015 | 36% | — | At 16 mg per kg, 15 patients had a partial response or better, including 2 with a complete response and 2 with a very good partial response; at 8 mg per kg, 3 had a partial response. Infusion-related reactions of any grade occurred in 71% of part 2 patients (grade 3 in 1%). |
| PFSPart 2, 16 mg/kg cohort | primaryLokhorst 2015 | median 5.6 months (4.2–8.1) | — | 65% (95% CI, 28 to 86) of the patients who had a response did not have progression at 12 months. |
| Endpoint | Analysis | Daratumumab 8 mg/kg (part 2 cohort) / Daratumumab 16 mg/kg (part 2 cohort) | Control | Effect |
|---|---|---|---|---|
| ORRPart 2 expansion cohorts | primaryLokhorst 2015 | 36% | — | At 16 mg per kg, 15 patients had a partial response or better, including 2 with a complete response and 2 with a very good partial response; at 8 mg per kg, 3 had a partial response. Infusion-related reactions of any grade occurred in 71% of part 2 patients (grade 3 in 1%). |
| PFSPart 2, 16 mg/kg cohort | primaryLokhorst 2015 | median 5.6 months (4.2–8.1) | — | 65% (95% CI, 28 to 86) of the patients who had a response did not have progression at 12 months. |
- Daratumumab 16 mg/kg (part 2 cohort) (experimental)
Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.
Data table (modelled values)
| Months | Daratumumab 16 mg/kg (part 2 cohort) |
|---|---|
| 0 | 100.0% |
| 4 | 61.0% |
| 7 | 42.0% |
| 11 | 25.6% |
| 14 | 17.7% |