Clinical trial NCT02088112: MEDI4736 (Anti PD-L1) Combined With Gefitinib in Subjects With Non-Small Cell Lung Cancer(NSCLC).
Official title: A Phase I, Open-Label, Multicentre Study to Assess the Safety, Tolerability, Pharmacokinetics and Preliminary Anti-tumour Activity of Gefitinib in Combination With MEDI4736 (Anti PD-L1) in Subjects With Non-Small Cell Lung Cancer(NSCLC)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Carcinoma, Non-Small-Cell Lung
Keywords: NSCLC
Lead sponsor: MedImmune LLC
Sponsor class: INDUSTRY
Collaborators: name: AstraZeneca
First posted: 2014-03-14
Enrollment: 56
Sex: ALL
Minimum age (years): 18
Maximum age (years): 130
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This a Phase I, Open-Label, Multicentre Study to assess the safety, tolerability, pharmacokinetics and preliminary anti-tumour activity of gefitinib in combination with MEDI4736 (anti PD-L1) in Subjects with Non-small cell lung cancer (NSCLC). The study consists of two phases: Escalation phase and an expansion phase to be conducted in locally advanced or metastatic NSCLC subjects

Detailed description: In Escalation phase: MEDI4736 and gefitinib in NSCLC subjects In Expansion phase: Subjects with EGFR mutation positive locally advanced or metastatic NSCLC will be enrolled in expansion arms. Initiation of expansion arms with the recommended dose of MEDI4736 in combination with gefitinib will be based on an adequate safety and tolerability profile of the combination from the escalation phase.

Eligibility criteria: Key Inclusion Criteria:

1. Provision of signed and dated, written informed consent
2. Male or female aged 18 years and older.
3. Subjects must have a. In the escalation phase, locally advanced or metastatic NSCLC subjects who have either failed to respond or relapsed following any line of standard treatment, were unable to tolerate, or were not eligible for standard treatment b. In the expansion phase, histologically or cytologically confirmed locally advanced or metastatic NSCLC that is EGFR mutation positive, naïve to EGFR TKI therapy, and sensitive to EGFR TKIs therapy
4. a.For Escalation Phase: At least one lesion (measurable and/or non-measurable) b.For Expansion Phase: At least one measurable lesion.
5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

   * For Japan Escalation - the same as the global escalation I/E criteria except patients must be EGFR mutation positive

Key Exclusion Criteria:

1. Any concurrent chemotherapy, immunotherapy, biologic, or hormonal therapy for cancer treatment.
2. Any investigational agent, chemotherapy, immunotherapy, biologic, hormonal within 28 days of the first dose of study treatment
3. Inadequate bone marrow reserve or organ function

Primary outcomes:
measure: Escalation Phase: safety and tolerability: AEs, laboratory data, vital signs, ECG changes and Echo. Expansion Phase: safety and tolerability of the recommended dose for MEDI4736; AEs, laboratory data, vital signs, ECG changes and Echo.
timeFrame: From first dose of study treatment until 90 days after the last dose, assessed up to 32 months
Secondary outcomes:
measure: To obtain a preliminary assessment of the anti-tumour activity of gefitinib in combination with MEDI4736 by evaluation of tumour response
timeFrame: From baseline assessment to disease progression, assessed up to 30 months
measure: To determine the immunogenicity of MEDI4736 in combination with gefitinib: anti-drug antibodies (ADAs)
timeFrame: From first dose of study treatment until 90 days after the last dose, assessed up to 32 months
measure: To determine the pharmacokinetics of MEDI4736
timeFrame: From first dose of study treatment until 90 days after the last dose, assessed up to 32 months
measure: To assess MEDI4736 pharmacodynamics in subjects receiving MEDI4736 in combination with gefitinib.
timeFrame: From first dose of study treatment until 90 days after the last dose, assessed up to 32 months
measure: To determine overall survival (OS) in expansion Arm 1 and Arm 1a patients
timeFrame: From final safety follow-up visit after last dose until 1 year after the final patient discontinues investigational product (initial Medi4736).
Other outcomes:
Locations:
city: Tampa
country: United States
facility: Research Site
state: Florida
city: Houston
country: United States
facility: Research Site
state: Texas
city: Seattle
country: United States
facility: Research Site
state: Washington
city: Chuo-ku
country: Japan
facility: Research Site
city: Matsuyama-shi
country: Japan
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
Study officials:
affiliation: Moffit Cancer Center
name: Ben Creelan, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: M.D. Anderson Cancer Center
name: Don Gibbons, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Washington
name: Laura Chow, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Asan Medical Center
name: Sang-We Kim, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Seoul National University Hospital
name: Dong-Wan Kim, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: National Cancer Center
name: Shinitaro Kanda, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Shikoku Cancer Center
name: Naoyuki Nogami
role: PRINCIPAL_INVESTIGATOR
References:
citation: Creelan BC, Yeh TC, Kim SW, Nogami N, Kim DW, Chow LQM, Kanda S, Taylor R, Tang W, Tang M, Angell HK, Roudier MP, Marotti M, Gibbons DL. A Phase 1 study of gefitinib combined with durvalumab in EGFR TKI-naive patients with EGFR mutation-positive locally advanced/metastatic non-small-cell lung cancer. Br J Cancer. 2021 Jan;124(2):383-390. doi: 10.1038/s41416-020-01099-7. Epub 2020 Oct 5.