Phase II Study of MEDI4736 Monotherapy or in Combinations With Tremelimumab in Metastatic Pancreatic Ductal Carcinoma

Brief summary public domain (ClinicalTrials.gov)

A Phase II Open-Label, Multi-Center Study of MEDI4736 Evaluated as Single Agent or in Combination with Tremelimumab in Patients with Metastatic Pancreatic Ductal Adenocarcinoma.

Detailed description public domain (ClinicalTrials.gov)

This is a Phase II, open-label, multi-center study to determine the efficacy and safety of MEDI4736 evaluated as single agent or in combination with tremelimumab in patients with metastatic pancreatic ductal adenocarcinoma (PDAC) whose disease has progressed on fluoropyrimidine containing or gemcitabine-containing first-line chemotherapy.This study will consist of Part A, lead-in, as well as a possible expansion Part B.

Posted results (ClinicalTrials.gov registry) · primary outcome public domain (ClinicalTrials.gov)

Objective Response Rate (ORR) in All Patients Using Investigator Assessments According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) [From date of first infusion until confirmed disease progression or death (up to approximately 18 months for the data analysis cut-off)]. Number, Percentage of participants (95% Confidence Interval). Confirmed responses only: Durvalumab (MEDI4736) Plus Tremelimumab (n=32): 3.1 (0.08 to 16.22); Durvalumab (MEDI4736) Monotherapy (n=33): 0 (0 to 10.58). Confirmed and unconfirmed responses: Durvalumab (MEDI4736) Plus Tremelimumab (n=32): 3.1 (0.08 to 16.22); Durvalumab (MEDI4736) Monotherapy (n=33): 6.1 (0.74 to 20.23).

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

Progression-free Survival (PFS) Using Investigator Assessments According to RECIST 1.1 [From date of first infusion until confirmed disease progression or death (up to approximately 18 months for the data analysis cut-off)]. Median, Months (95% Confidence Interval). Durvalumab (MEDI4736) Plus Tremelimumab (n=32): 1.5 (1.2 to 1.5); Durvalumab (MEDI4736) Monotherapy (n=33): 1.5 (1.3 to 1.5).

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

PFS Rate at 3 Months and at 6 Months [From date of first infusion until confirmed disease progression or death (up to 3 months and 6 months)]. Number, Percentage of participants (95% Confidence Interval). PFS rate at 3 months: Durvalumab (MEDI4736) Plus Tremelimumab (n=32): 9.4 (2.4 to 22.3); Durvalumab (MEDI4736) Monotherapy (n=33): 10.9 (3.0 to 24.7). PFS rate at 6 months: Durvalumab (MEDI4736) Plus Tremelimumab (n=32): 9.4 (2.4 to 22.3); Durvalumab (MEDI4736) Monotherapy (n=33): 3.6 (0.3 to 15.4).

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

Overall Survival (OS) [From date of first infusion until death (up to approximately 18 months for the data analysis cut-off)]. Median, Months (95% Confidence Interval). Durvalumab (MEDI4736) Plus Tremelimumab (n=32): 3.1 (2.2 to 6.1); Durvalumab (MEDI4736) Monotherapy (n=33): 3.6 (2.7 to 6.1).

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

Survival Status, Presented as OS Rate, at 6 Months and at 12 Months [From date of first infusion until death (up to 6 months and 12 months)]. Number, Percentage of participants (95% Confidence Interval). Survival rate at 6 months: Durvalumab (MEDI4736) Plus Tremelimumab (n=32): 36.2 (20.0 to 52.7); Durvalumab (MEDI4736) Monotherapy (n=33): 34.9 (19.2 to 51.1). Survival rate at 12 months: Durvalumab (MEDI4736) Plus Tremelimumab (n=32): 8.8 (1.8 to 22.8); Durvalumab (MEDI4736) Monotherapy (n=33): 6.3 (1.1 to 18.4).

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

Best Objective Response (BoR) Using Investigator Assessments According to RECIST 1.1 [From date of first infusion until confirmed disease progression or death (up to approximately 18 months for the data analysis cut-off)]. Count Of Participants, Participants. Response: Total: Durvalumab (MEDI4736) Plus Tremelimumab (n=32): 1; Durvalumab (MEDI4736) Monotherapy (n=33): 0. Response: CR: Durvalumab (MEDI4736) Plus Tremelimumab (n=32): 0; Durvalumab (MEDI4736) Monotherapy (n=33): 0. Response: PR: Durvalumab (MEDI4736) Plus Tremelimumab (n=32): 1; Durvalumab (MEDI4736) Monotherapy (n=33): 0. Non-response: Total: Durvalumab (MEDI4736) Plus Tremelimumab (n=32): 31; Durvalumab (MEDI4736) Monotherapy (n=33): 33. Non-response: Stable disease ≥6 weeks: Durvalumab (MEDI4736) Plus Tremelimumab (n=32): 5; Durvalumab (MEDI4736) Monotherapy (n=33): 7. Non-response: Progression of disease: Durvalumab (MEDI4736) Plus Tremelimumab (n=32): 26; Durvalumab (MEDI4736) Monotherapy (n=33): 25. Non-response: Not evaluable: Durvalumab (MEDI4736) Plus Tremelimumab (n=32): 0; Durvalumab (MEDI4736) Monotherapy (n=33): 1.

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

Disease Control Rate (DCR) Using Investigator Assessments According to RECIST 1.1 [From date of first infusion until confirmed disease progression or death (up to 3 months, 6 months and 12 months)]. Number, Percentage of participants (95% Confidence Interval). At 3 months: Durvalumab (MEDI4736) Plus Tremelimumab (n=32): 9.4 (1.98 to 25.02); Durvalumab (MEDI4736) Monotherapy (n=33): 6.1 (0.74 to 20.23). At 6 months: Durvalumab (MEDI4736) Plus Tremelimumab (n=32): 6.3 (0.77 to 20.81); Durvalumab (MEDI4736) Monotherapy (n=33): 0 (0.00 to 10.58). At 12 months: Durvalumab (MEDI4736) Plus Tremelimumab (n=32): 3.1 (0.08 to 16.22); Durvalumab (MEDI4736) Monotherapy (n=33): 0 (0.00 to 10.58).

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

Pharmacokinetics (PK) of Durvalumab (MEDI4736) [Blood samples were collected pre-dose on Day 1 (Week 0), Week 4, Week 12 and Week 24, post-dose on Day 1, Week 12 and Week 24, and additionally at 3 months after the last dose (follow-up).]. Mean, Micrograms per millilitre (mcg/mL) (Standard Deviation). Cycle 1, Day 1, pre-infusion (Day 1): Durvalumab (MEDI4736) Plus Tremelimumab (n=32): 217.338 (345.4913). Cycle 1, Day 1, post-infusion (Day 1): Durvalumab (MEDI4736) Plus Tremelimumab (n=32): 566.078 (151.4199); Durvalumab (MEDI4736) Monotherapy (n=32): 562.218 (152.3811). Cycle 2, Day 1, pre-infusion (Day 29): Durvalumab (MEDI4736) Plus Tremelimumab (n=32): 100.417 (39.7229); Durvalumab (MEDI4736) Monotherapy (n=32): 98.668 (36.5072). Cycle 4, Day 1, pre-infusion (Day 85): Durvalumab (MEDI4736) Plus Tremelimumab (n=32): 236.205 (98.8964); Durvalumab (MEDI4736) Monotherapy (n=32): 228.450 (36.8395). Cycle 4, Day 1, post-infusion (Day 85): Durvalumab (MEDI4736) Plus Tremelimumab (n=32): 825.818 (322.8247); Durvalumab (MEDI4736) Monotherapy (n=32): 760.456 (100.6974). Cycle 7, Day 1, pre-infusion (Day 169): Durvalumab (MEDI4736) Plus Tremelimumab (n=32): 166.736 (47.3872); Durvalumab (MEDI4736) Monotherapy (n=32): 152.706 (NA) [Data applies to one patient so standard deviation value not applicable.]. Cycle 7, Day 1, post-infusion (Day169): Durvalumab (MEDI4736) Plus Tremelimumab (n=32): 918.270 (98.4286); Durvalumab (MEDI4736) Monotherapy (n=32): 825.578 (NA) [Data applies to one patient so standard deviation value not applicable.]. 3-month follow-up: Durvalumab (MEDI4736) Plus Tremelimumab (n=32): 38.456 (NA) [Data applies to one patient so standard deviation value not applicable.]; Durvalumab (MEDI4736) Monotherapy (n=32): 19.684 (20.2664).

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

PK of Tremelimumab [Blood samples were collected pre-dose on Day 1 (Week 0), Week 4 and Week 12, post-dose on Day 1 and Week 12, and additionally at 3 months after the last dose (follow-up).]. Mean, mcg/mL (Standard Deviation). Cycle 1, Day 1, pre-infusion (Day 1): Durvalumab (MEDI4736) Plus Tremelimumab (n=32): 13.114 (11.7182). Cycle 1, Day 1, post-infusion (Day 1): Durvalumab (MEDI4736) Plus Tremelimumab (n=32): 24.477 (6.3516). Cycle 2, Day 1, pre-infusion (Day 29): Durvalumab (MEDI4736) Plus Tremelimumab (n=32): 4.880 (2.2623). Cycle 4, Day 1, pre-infusion (Day 85): Durvalumab (MEDI4736) Plus Tremelimumab (n=32): 8.753 (4.9962). Cycle 4, Day 1, post-infusion (Day 85): Durvalumab (MEDI4736) Plus Tremelimumab (n=32): 21.150 (5.8997).

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

Presence of Antidrug Antibodies (ADAs) for Durvalumab (MEDI4736) [Immunogenicity samples were collected on Day 1 (Week 0), Week 4, Week 12 and Week 24, and additionally at 3 months and 6 months after the last dose (follow-up).]. Count Of Participants, Participants. ADA prevalence: Durvalumab (MEDI4736) Plus Tremelimumab (n=25): 1; Durvalumab (MEDI4736) Monotherapy (n=24): 5. ADA incidence: Durvalumab (MEDI4736) Plus Tremelimumab (n=25): 0; Durvalumab (MEDI4736) Monotherapy (n=24): 3. ADA pos post-baseline and pos at baseline: Durvalumab (MEDI4736) Plus Tremelimumab (n=25): 0; Durvalumab (MEDI4736) Monotherapy (n=24): 0. ADA pos post-baseline and not detected at baseline: Durvalumab (MEDI4736) Plus Tremelimumab (n=25): 0; Durvalumab (MEDI4736) Monotherapy (n=24): 3. ADA not detected post-baseline and pos at baseline: Durvalumab (MEDI4736) Plus Tremelimumab (n=25): 1; Durvalumab (MEDI4736) Monotherapy (n=24): 2. Treatment-boosted ADA: Durvalumab (MEDI4736) Plus Tremelimumab (n=25): 0; Durvalumab (MEDI4736) Monotherapy (n=24): 0. Persistent positive: Durvalumab (MEDI4736) Plus Tremelimumab (n=25): 0; Durvalumab (MEDI4736) Monotherapy (n=24): 3. Transient positive: Durvalumab (MEDI4736) Plus Tremelimumab (n=25): 0; Durvalumab (MEDI4736) Monotherapy (n=24): 0. Never positive: Durvalumab (MEDI4736) Plus Tremelimumab (n=25): 24; Durvalumab (MEDI4736) Monotherapy (n=24): 19.

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

Presence of ADAs for Tremelimumab [Immunogenicity samples were collected on Day 1 (Week 0), Week 4 and Week 12, and additionally at 3 months and 6 months after the last dose (follow-up).]. Count Of Participants, Participants. ADA prevalence: Durvalumab (MEDI4736) Plus Tremelimumab (n=25): 2. ADA incidence: Durvalumab (MEDI4736) Plus Tremelimumab (n=25): 0. ADA pos post-baseline and pos at baseline: Durvalumab (MEDI4736) Plus Tremelimumab (n=25): 1. ADA pos post-baseline and not detected at baseline: Durvalumab (MEDI4736) Plus Tremelimumab (n=25): 0. ADA not detected post-baseline and pos at baseline: Durvalumab (MEDI4736) Plus Tremelimumab (n=25): 1. Treatment-boosted ADA: Durvalumab (MEDI4736) Plus Tremelimumab (n=25): 0. Persistent positive: Durvalumab (MEDI4736) Plus Tremelimumab (n=25): 0. Transient positive: Durvalumab (MEDI4736) Plus Tremelimumab (n=25): 1. Never positive: Durvalumab (MEDI4736) Plus Tremelimumab (n=25): 23.