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Y. Huang
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P2.04 - Clinical Design, Statistics and Clinical Trials (ID 705)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Clinical Design, Statistics and Clinical Trials
- Presentations: 2
- Moderators:
- Coordinates: 10/17/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P2.04-001 - BALTIC: A Phase 2, Open-Label Study of Novel Combinations of Immunotherapies or DDR Inhibitors in Platinum-Refractory ED-SCLC (ID 8668)
09:30 - 09:30 | Author(s): Y. Huang
- Abstract
Background:
Immunotherapy and DNA damage repair inhibitors have the potential to play a role in the treatment of patients with extensive-disease small cell lung cancer (ED-SCLC), due to high mutation load and genomic instability in this disease setting. Durvalumab, a selective, high-affinity, engineered human IgG1 mAb blocks PD-L1 binding to PD-1 and CD80. Tremelimumab is a selective human IgG2 mAb targeting CTLA-4. Durvalumab plus tremelimumab demonstrated clinical activity and manageable tolerability in a Phase 1b study in NSCLC (NCT02000947). AZD1775, a small-molecule inhibitor of DNA damage checkpoint kinase WEE1, potentiates genotoxic chemotherapies. AZD1775 plus carboplatin showed antitumor activity and acceptable safety in a Phase 2 study in platinum-refractory p53-mutated ovarian cancer (NCT01164995).
Method:
BALTIC (NCT02937818) is a Phase 2, open-label, multicenter, multi-arm, exploratory, signal-searching study to assess the preliminary activity of novel treatment combinations in patients with platinum-refractory/resistant ED-SCLC. Inclusion criteria include disease progression during, or within 90 days of completing, first-line platinum-based chemotherapy; WHO/ECOG performance status of 0/1; and life expectancy ≥8 weeks. Each study arm is independent and will open sequentially to enroll up to 20 patients. The study will open initially with two arms. Patients will receive durvalumab 1500 mg + tremelimumab 75 mg i.v. q4w for 4 doses, followed by durvalumab monotherapy 1500 mg i.v. q4w (Arm A); and oral AZD1775 225 mg bid for 2.5 days from Day 1 + carboplatin AUC 5 on Day 1 i.v. q3w (Arm B). Treatment will continue until confirmed disease progression or discontinuation. Further arms will be added to assess other combinations once tolerable dosing regimens have been established. The primary endpoint is investigator-assessed ORR (RECIST v1.1). Secondary endpoints include duration of response, disease control rate, time-to-response, PFS, OS, pharmacokinetics, safety and tolerability. Gene expression levels and biomarkers will also be explored. Recruitment is ongoing.Figure 1
Result:
Section not applicable
Conclusion:
Section not applicable
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P2.04-002 - CASPIAN: Phase 3 Study of First-Line Durvalumab ± Tremelimumab + Platinum-Based Chemotherapy vs Chemotherapy Alone in ED-SCLC (ID 8672)
09:30 - 09:30 | Author(s): Y. Huang
- Abstract
Background:
New therapies are urgently needed for patients with extensive-disease small cell lung cancer (ED-SCLC). High mutation burden in SCLC suggests a potential role for immune checkpoint blockade. Durvalumab is a selective, high-affinity, engineered human IgG1 mAb that blocks PD-L1 binding to PD-1 and CD80. Tremelimumab is a selective human IgG2 mAb against CTLA-4. Durvalumab ± tremelimumab in combination with chemotherapy has shown acceptable tolerability and evidence of clinical activity in a Phase 1b study (NCT02537418) in patients with advanced solid tumors, including NSCLC and SCLC.
Method:
CASPIAN (NCT03043872) is a Phase 3, randomized, multicenter, open-label, global study investigating the combination of first-line chemotherapy with durvalumab ± tremelimumab in Stage IV ED-SCLC. Treatment-naïve patients (N=795) will be randomized 1:1:1 to receive durvalumab 1500 mg + tremelimumab 75 mg i.v. q3w + chemotherapy (Arm 1); durvalumab 1500 mg i.v. q3w + chemotherapy (Arm 2); or chemotherapy alone (Arm 3). Durvalumab ± tremelimumab will be concurrently administered with chemotherapy in Arms 1 and 2 and will continue post chemotherapy (one further dose for tremelimumab; until disease progression for durvalumab). Chemotherapy (etoposide with either carboplatin or cisplatin) will be given for up to 4 cycles in Arms 1 and 2 and up to 6 cycles in Arm 3. Co-primary endpoints are OS and PFS using blinded independent central review (RECIST v1.1; Arm 1 vs Arm 3). Secondary endpoints include OS and PFS (Arm 2 vs Arm 3, Arm 1 vs Arm 2); ORR; 18-month OS; proportion of patients alive and progression-free at 6 and 12 months; pharmacokinetics; immunogenicity; HRQoL; safety and tolerability. An independent data monitoring committee will meet at two early stages of enrolment to confirm the safety and tolerability of the proposed combination dosing regimen and will monitor safety every 6 months thereafter. Recruitment is ongoing. Figure 1
Result:
Section not applicable
Conclusion:
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