KEYTRUDA (Page 10 of 21)
14.4 Classical Hodgkin Lymphoma
KEYNOTE-204
The efficacy of KEYTRUDA was investigated in KEYNOTE-204 (NCT02684292), a randomized, open-label, active controlled trial conducted in 304 patients with relapsed or refractory cHL. The trial enrolled adults with relapsed or refractory disease after at least one multi-agent chemotherapy regimen. Patients were randomized (1:1) to receive:
- KEYTRUDA 200 mg intravenously every 3 weeks or
- Brentuximab vedotin (BV) 1.8 mg/kg intravenously every 3 weeks
Treatment was continued until unacceptable toxicity, disease progression, or a maximum of 35 cycles (up to approximately 2 years). Disease assessment was performed every 12 weeks. Randomization was stratified by prior autologous HSCT (yes vs. no) and disease status after frontline therapy (primary refractory vs. relapse <12 months after completion vs. relapse ≥12 months after completion). The main efficacy measure was PFS as assessed by BICR using 2007 revised International Working Group criteria.
The study population characteristics were: median age of 35 years (range: 18 to 84); 57% male; 77% White, 9% Asian, 3.9% Black. The median number of prior therapies was 2 (range: 1 to 10) in the KEYTRUDA arm and 3 (range: 1 to 11) in the BV arm, with 18% in both arms having 1 prior line. Forty-two percent of patients were refractory to the last prior therapy, 29% had primary refractory disease, 37% had prior autologous HSCT, 5% had received prior BV, and 39% had prior radiation therapy.
Efficacy is summarized in Table 60 and Figure 13.
| Endpoint | KEYTRUDA200 mg every 3 weeksn=151 | Brentuximab Vedotin1.8 mg/kg every 3 weeksn=153 |
|---|---|---|
| + Denotes a censored value. | ||
| PFS | ||
| Number of patients with event (%) | 81 (54%) | 88 (58%) |
| Median in months (95% CI)* | 13.2 (10.9, 19.4) | 8.3 (5.7, 8.8) |
| Hazard ratio † (95% CI) | 0.65 (0.48, 0.88) | |
| p-Value ‡ | 0.0027 | |
| Objective Response Rate | ||
| ORR § (95% CI) | 66% (57, 73) | 54% (46, 62) |
| Complete response | 25% | 24% |
| Partial response | 41% | 30% |
| Duration of Response | ||
| Median in months (range)* | 20.7 (0.0+, 33.2+) | 13.8 (0.0+, 33.9+) |
KEYNOTE-087
The efficacy of KEYTRUDA was investigated in KEYNOTE-087 (NCT02453594), a multicenter, non-randomized, open-label trial in 210 patients with relapsed or refractory cHL. Patients with active, non-infectious pneumonitis, an allogeneic HSCT within the past 5 years (or >5 years but with symptoms of GVHD), active autoimmune disease, a medical condition that required immunosuppression, or an active infection requiring systemic therapy were ineligible for the trial. Patients received KEYTRUDA 200 mg intravenously every 3 weeks until unacceptable toxicity or documented disease progression, or for up to 24 months in patients who did not progress. Disease assessment was performed every 12 weeks. The major efficacy outcome measures (ORR, Complete Response Rate, and DoR) were assessed by BICR according to the 2007 revised International Working Group (IWG) criteria.
The study population characteristics were: median age of 35 years (range: 18 to 76), 9% age 65 or older; 54% male; 88% White; and 49% ECOG PS of 0 and 51% ECOG PS of 1. The median number of prior lines of therapy administered for the treatment of cHL was 4 (range: 1 to 12). Fifty-eight percent were refractory to the last prior therapy, including 35% with primary refractory disease and 14% whose disease was chemo-refractory to all prior regimens. Sixty-one percent of patients had undergone prior autologous HSCT, 83% had received prior brentuximab vedotin and 36% of patients had prior radiation therapy.
Efficacy results for KEYNOTE-087 are summarized in Table 61.
| Endpoint | KEYTRUDA200 mg every 3 weeksn=210* |
|---|---|
| Objective Response Rate | |
| ORR (95% CI) | 69% (62, 75) |
| Complete response rate | 22% |
| Partial response rate | 47% |
| Duration of Response | |
| Median in months (range) | 11.1 (0.0+, 11.1)† |
14.5 Primary Mediastinal Large B-Cell Lymphoma
The efficacy of KEYTRUDA was investigated in KEYNOTE-170 (NCT02576990), a multicenter, open-label, single-arm trial in 53 patients with relapsed or refractory PMBCL. Patients were not eligible if they had active non-infectious pneumonitis, allogeneic HSCT within the past 5 years (or >5 years but with symptoms of GVHD), active autoimmune disease, a medical condition that required immunosuppression, or an active infection requiring systemic therapy. Patients were treated with KEYTRUDA 200 mg intravenously every 3 weeks until unacceptable toxicity or documented disease progression, or for up to 24 months for patients who did not progress. Disease assessments were performed every 12 weeks and assessed by BICR according to the 2007 revised IWG criteria. The efficacy outcome measures were ORR and DoR.
The study population characteristics were: median age of 33 years (range: 20 to 61 years); 43% male; 92% White; and 43% ECOG PS of 0 and 57% ECOG PS of 1. The median number of prior lines of therapy administered for the treatment of PMBCL was 3 (range 2 to 8). Thirty-six percent had primary refractory disease, 49% had relapsed disease refractory to the last prior therapy, and 15% had untreated relapse. Twenty-six percent of patients had undergone prior autologous HSCT, and 32% of patients had prior radiation therapy. All patients had received rituximab as part of a prior line of therapy.
For the 24 responders, the median time to first objective response (complete or partial response) was 2.8 months (range 2.1 to 8.5 months). Efficacy results for KEYNOTE-170 are summarized in Table 62.
| Endpoint | KEYTRUDA200 mg every 3 weeksn=53* |
|---|---|
| NR = not reached | |
| Objective Response Rate | |
| ORR (95% CI) | 45% (32, 60) |
| Complete response rate | 11% |
| Partial response rate | 34% |
| Duration of Response | |
| Median in months (range) | NR (1.1+, 19.2+)† |
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