SIRIUS
Daratumumab monotherapy in patients with treatment-refractory multiple myeloma (SIRIUS): an open-label, randomised, phase 2 trial
Phase 2NCT01985126
- Population
- Myeloma treated with at least three lines (including proteasome inhibitors and immunomodulatory drugs) or refractory to both; median of five previous lines, 95% refractory to the last proteasome inhibitor and immunomodulatory drug.
- Design
- Open-label, multicentre phase 2 trial. Part 1 stage 1 randomised patients 1:1 to daratumumab 8 or 16 mg per kg to choose the dose; patients in part 1 stage 2 and part 2 received 16 mg per kg. Findings are reported for the patients who received 16 mg per kg in parts 1 and 2.
- Primary endpoint
- ORR
- Arms
- Daratumumab 16 mg/kg (experimental, n = 106): Daratumumab 16 mg per kg: weekly for 8 weeks, every 2 weeks for 16 weeks, then every 4 weeks
- Daratumumab 8 mg/kg (dose selection, stage 1) (experimental, n = 18): Daratumumab 8 mg per kg every 4 weeks
- People
- Lonial S
Show the numbers
| Endpoint | Analysis | Daratumumab 16 mg/kg / Daratumumab 8 mg/kg (dose selection, stage 1) | Control | Effect |
|---|---|---|---|---|
| ORRPatients who received 16 mg/kg in parts 1 and 2 (106) | primaryLonial 2016 | 29.2% (20.8–38.9%) | — | Of the 31 responders, 3 (2.8%) had a stringent complete response, 10 (9.4%) a very good partial response and 18 (17.0%) a partial response. Median time to first response was 1.0 month. |
| DORPatients who received 16 mg/kg in parts 1 and 2 (106) | primaryLonial 2016 | median 7.4 months | — | 95% CI 5.5 to not estimable (lower bound only, so no interval is recorded). |
| PFSPatients who received 16 mg/kg in parts 1 and 2 (106) | primaryLonial 2016 | median 3.7 months (2.8–4.6) | — | — |
| OSPatients who received 16 mg/kg in parts 1 and 2 (106) | primaryLonial 2016 | median 17.5 months; 64.8% at 12 mo (51.2–75.5%) | — | The 12-month rate and the median (95% CI 13.7 to not estimable, lower bound only) come from different data cutoffs. |
| Endpoint | Analysis | Daratumumab 16 mg/kg / Daratumumab 8 mg/kg (dose selection, stage 1) | Control | Effect |
|---|---|---|---|---|
| ORRPatients who received 16 mg/kg in parts 1 and 2 (106) | primaryLonial 2016 | 29.2% (20.8–38.9%) | — | Of the 31 responders, 3 (2.8%) had a stringent complete response, 10 (9.4%) a very good partial response and 18 (17.0%) a partial response. Median time to first response was 1.0 month. |
| DORPatients who received 16 mg/kg in parts 1 and 2 (106) | primaryLonial 2016 | median 7.4 months | — | 95% CI 5.5 to not estimable (lower bound only, so no interval is recorded). |
| PFSPatients who received 16 mg/kg in parts 1 and 2 (106) | primaryLonial 2016 | median 3.7 months (2.8–4.6) | — | — |
| OSPatients who received 16 mg/kg in parts 1 and 2 (106) | primaryLonial 2016 | median 17.5 months; 64.8% at 12 mo (51.2–75.5%) | — | The 12-month rate and the median (95% CI 13.7 to not estimable, lower bound only) come from different data cutoffs. |
- Daratumumab 16 mg/kg (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 |
|---|---|
| 0 | 100.0% |
| 5 | 62.6% |
| 9 | 43.0% |
| 14 | 26.9% |
| 19 | 16.9% |
- Daratumumab 16 mg/kg (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 |
|---|---|
| 0 | 100.0% |
| 2 | 68.8% |
| 5 | 39.2% |
| 7 | 26.9% |
| 9 | 18.5% |