A Phase III, Randomized, Placebo-controlled, Double-blind, Multi-center, International Study of Durvalumab Given Concurrently With Platinum-based Chemoradiation Therapy in Patients With Locally Advanced, Unresectable NSCLC (Stage III) (PACIFIC2)
Overview
- Phase
- Phase 3
- Intervention
- Durvalumab
- Conditions
- Non-Small Cell Lung Cancer
- Sponsor
- AstraZeneca
- Enrollment
- 328
- Locations
- 1
- Primary Endpoint
- Progression-Free Survival (PFS)
- Status
- Active, not recruiting
- Last Updated
- 6 months ago
Overview
Brief Summary
This is a Phase III, randomized, double-blind, placebo-controlled, multi-center, international study assessing the efficacy and safety of durvalumab given concurrently with platinum-based CRT (durvalumab + standard of care [SoC] CRT) in patients with locally advanced, unresectable NSCLC (Stage III).
Investigators
Eligibility Criteria
Inclusion Criteria
- Not provided
Exclusion Criteria
- Not provided
Arms & Interventions
Arm 1: Durvalumab + platinum-based chemotherapy and radiation
Durvalumab ((MEDI4736) in concurrence with platinum-based chemo-radiation therapy. All patients will receive 1 of the following platinum-based standard of care chemotherapy options, based on Investigator discretion, in addition to radiation therapy: * cisplatin/etoposide * carboplatin/paclitaxel * pemetrexed/cisplatin * pemetrexed/carboplatin At the completion of standard of care chemoradiation therapy (SoC CRT), patients with complete response, partial response or stable disease will continue to receive durvalumab as consolidation treatment.
Intervention: Durvalumab
Arm 1: Durvalumab + platinum-based chemotherapy and radiation
Durvalumab ((MEDI4736) in concurrence with platinum-based chemo-radiation therapy. All patients will receive 1 of the following platinum-based standard of care chemotherapy options, based on Investigator discretion, in addition to radiation therapy: * cisplatin/etoposide * carboplatin/paclitaxel * pemetrexed/cisplatin * pemetrexed/carboplatin At the completion of standard of care chemoradiation therapy (SoC CRT), patients with complete response, partial response or stable disease will continue to receive durvalumab as consolidation treatment.
Intervention: Cisplatin/ Etoposide
Arm 1: Durvalumab + platinum-based chemotherapy and radiation
Durvalumab ((MEDI4736) in concurrence with platinum-based chemo-radiation therapy. All patients will receive 1 of the following platinum-based standard of care chemotherapy options, based on Investigator discretion, in addition to radiation therapy: * cisplatin/etoposide * carboplatin/paclitaxel * pemetrexed/cisplatin * pemetrexed/carboplatin At the completion of standard of care chemoradiation therapy (SoC CRT), patients with complete response, partial response or stable disease will continue to receive durvalumab as consolidation treatment.
Intervention: Carboplatin/ Paclitaxel
Arm 1: Durvalumab + platinum-based chemotherapy and radiation
Durvalumab ((MEDI4736) in concurrence with platinum-based chemo-radiation therapy. All patients will receive 1 of the following platinum-based standard of care chemotherapy options, based on Investigator discretion, in addition to radiation therapy: * cisplatin/etoposide * carboplatin/paclitaxel * pemetrexed/cisplatin * pemetrexed/carboplatin At the completion of standard of care chemoradiation therapy (SoC CRT), patients with complete response, partial response or stable disease will continue to receive durvalumab as consolidation treatment.
Intervention: Pemetrexed/ Cisplatin
Arm 1: Durvalumab + platinum-based chemotherapy and radiation
Durvalumab ((MEDI4736) in concurrence with platinum-based chemo-radiation therapy. All patients will receive 1 of the following platinum-based standard of care chemotherapy options, based on Investigator discretion, in addition to radiation therapy: * cisplatin/etoposide * carboplatin/paclitaxel * pemetrexed/cisplatin * pemetrexed/carboplatin At the completion of standard of care chemoradiation therapy (SoC CRT), patients with complete response, partial response or stable disease will continue to receive durvalumab as consolidation treatment.
Intervention: Pemetrexed/ Carboplatin
Arm 1: Durvalumab + platinum-based chemotherapy and radiation
Durvalumab ((MEDI4736) in concurrence with platinum-based chemo-radiation therapy. All patients will receive 1 of the following platinum-based standard of care chemotherapy options, based on Investigator discretion, in addition to radiation therapy: * cisplatin/etoposide * carboplatin/paclitaxel * pemetrexed/cisplatin * pemetrexed/carboplatin At the completion of standard of care chemoradiation therapy (SoC CRT), patients with complete response, partial response or stable disease will continue to receive durvalumab as consolidation treatment.
Intervention: Radiation
Arm 2: Placebo + platinum-based chemotherapy and radiation
Placebo in concurrence with platinum-based chemo-radiation therapy. All patients will receive 1 of the following platinum-based standard of care chemotherapy options, based on Investigator discretion, in addition to radiation therapy: * cisplatin/etoposide * carboplatin/paclitaxel * pemetrexed/cisplatin * pemetrexed/carboplatin At the completion of standard of care chemoradiation therapy (SoC CRT), patients with complete response, partial response or stable disease will continue to receive placebo as consolidation treatment.
Intervention: Placebo
Arm 2: Placebo + platinum-based chemotherapy and radiation
Placebo in concurrence with platinum-based chemo-radiation therapy. All patients will receive 1 of the following platinum-based standard of care chemotherapy options, based on Investigator discretion, in addition to radiation therapy: * cisplatin/etoposide * carboplatin/paclitaxel * pemetrexed/cisplatin * pemetrexed/carboplatin At the completion of standard of care chemoradiation therapy (SoC CRT), patients with complete response, partial response or stable disease will continue to receive placebo as consolidation treatment.
Intervention: Cisplatin/ Etoposide
Arm 2: Placebo + platinum-based chemotherapy and radiation
Placebo in concurrence with platinum-based chemo-radiation therapy. All patients will receive 1 of the following platinum-based standard of care chemotherapy options, based on Investigator discretion, in addition to radiation therapy: * cisplatin/etoposide * carboplatin/paclitaxel * pemetrexed/cisplatin * pemetrexed/carboplatin At the completion of standard of care chemoradiation therapy (SoC CRT), patients with complete response, partial response or stable disease will continue to receive placebo as consolidation treatment.
Intervention: Carboplatin/ Paclitaxel
Arm 2: Placebo + platinum-based chemotherapy and radiation
Placebo in concurrence with platinum-based chemo-radiation therapy. All patients will receive 1 of the following platinum-based standard of care chemotherapy options, based on Investigator discretion, in addition to radiation therapy: * cisplatin/etoposide * carboplatin/paclitaxel * pemetrexed/cisplatin * pemetrexed/carboplatin At the completion of standard of care chemoradiation therapy (SoC CRT), patients with complete response, partial response or stable disease will continue to receive placebo as consolidation treatment.
Intervention: Pemetrexed/ Cisplatin
Arm 2: Placebo + platinum-based chemotherapy and radiation
Placebo in concurrence with platinum-based chemo-radiation therapy. All patients will receive 1 of the following platinum-based standard of care chemotherapy options, based on Investigator discretion, in addition to radiation therapy: * cisplatin/etoposide * carboplatin/paclitaxel * pemetrexed/cisplatin * pemetrexed/carboplatin At the completion of standard of care chemoradiation therapy (SoC CRT), patients with complete response, partial response or stable disease will continue to receive placebo as consolidation treatment.
Intervention: Pemetrexed/ Carboplatin
Arm 2: Placebo + platinum-based chemotherapy and radiation
Placebo in concurrence with platinum-based chemo-radiation therapy. All patients will receive 1 of the following platinum-based standard of care chemotherapy options, based on Investigator discretion, in addition to radiation therapy: * cisplatin/etoposide * carboplatin/paclitaxel * pemetrexed/cisplatin * pemetrexed/carboplatin At the completion of standard of care chemoradiation therapy (SoC CRT), patients with complete response, partial response or stable disease will continue to receive placebo as consolidation treatment.
Intervention: Radiation
Outcomes
Primary Outcomes
Progression-Free Survival (PFS)
Time Frame: Tumour scans performed at screening, 16 weeks ±1 week after randomization, then every 8 weeks ±1 week up to 48 weeks, and then every 12 weeks ±1 week thereafter until confirmed PD. Assessed up to the DCO date (a maximum of approximately 1988 days).
The PFS per Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST 1.1) using blinded independent central review (BICR) assessments was defined as the time from the date of randomization until the date of objective PD or death (by any cause in the absence of progression) regardless of whether the participant withdrew from therapy or received another anti-cancer therapy prior to progression. The PD was defined as at least a 20% increase in the sum of diameters of target lesions. Median PFS was calculated using the Kaplan-Meier technique.
Secondary Outcomes
- Number of Participants With Anti-Drug Antibody (ADA) Response to Durvalumab(Pre-dose on Day 1 of Cycles 1, 2 and 4)
- Change From Baseline in Disease-Related Symptoms as Assessed by European Organisation for Research and Treatment of Cancer Quality of Life Questionnaires (EORTC QLQ) at Average Over 12 Months(At screening, 2, 4, 6, 8, 12, 16, and 20 weeks after randomization, then every 8 weeks ±1 week up to 52 weeks, and then every 12 weeks ±1 week thereafter until PFS2. Assessed up to 12 months.)
- Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)(From time of signature of informed consent up to 90 days after last dose of study treatment or up to the date of initiation of the first subsequent therapy, whichever occurs first, approximately 1988 days.)
- Objective Response Rate (ORR)(Tumour scans performed at screening, 16 weeks ±1 week after randomization, then every 8 weeks ±1 week up to 48 weeks, and then every 12 weeks ±1 week thereafter until confirmed PD. Assessed up to the DCO date (a maximum of approximately 1988 days).)
- Overall Survival (OS)(From screening until confirmed PD, assessed up to the DCO date (a maximum of approximately 1988 days).)
- Percentage of Participants Alive at 24 Months From Randomization (OS24)(Month 24)
- Complete Response Rate (CRR)(Tumour scans performed at screening, 16 weeks ±1 week after randomization, then every 8 weeks ±1 week up to 48 weeks, and then every 12 weeks ±1 week thereafter until confirmed PD. Assessed up to the DCO date (a maximum of approximately 1988 days).)
- Duration of Response (DoR)(Tumour scans performed at screening, 16 weeks ±1 week after randomization, then every 8 weeks ±1 week up to 48 weeks, and then every 12 weeks ±1 week thereafter until confirmed PD. Assessed up to the DCO date (a maximum of approximately 1988 days).)
- Disease Control Rate (DCR)(Week 24)
- Time to Death or Distant Metastasis (TTDM)(Tumour scans performed at screening, 16 weeks ±1 week after randomization, then every 8 weeks ±1 week up to 48 weeks, and then every 12 weeks ±1 week thereafter until confirmed PD. Assessed up to the DCO date (a maximum of approximately 1988 days).)
- Time From Randomization to Second Progression (PFS2)(Tumour scans performed at screening, 16 weeks ±1 week after randomization, then every 8 weeks ±1 week up to 48 weeks, and then every 12 weeks ±1 week thereafter until confirmed PD. Assessed up to the DCO date (a maximum of approximately 1988 days).)
- Serum Concentration of Durvalumab(End of infusion on Week 0, pre-infusion on Weeks 4 and 12, and Month 3 follow-up)