non small cell lung cancer (NSCLC)
Conditions
Interventions
Treatment with GSK3377794 with or without pembrolizumab.
Sponsors
GlaxoSmithKline
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: SCREENING: • Male or female, age 18 years and above. • Histologically or cytologically diagnosed unresectable Stage IIIb or Stage IV NSCLC. Measurable disease is not an indispensable requirement for enrollment/leukapheresis. • ECOG performance status 0-1. • Life expectancy of at least 3 months. • Left ventricular ejection fraction >=50% or as per institution*s guidelines. • Adequate venous access for leukapheresis. • Participant is positive for any of the following alleles: HLA-A*02:01, HLA A*02:05, HLA-A*02:06. • Tumor tissue (archival biopsy) obtained at any time from the initial diagnosis to time of study entry is mandatory for tumor antigen expression analysis (NY-ESO-1 and/or LAGE1a). In case an archival biopsy is not available a fresh biopsy may be considered in consultation with the sponsor. LEUKAPHERESIS: • Successfully completed screening: HLA-A*02:01, HLA-A*02:05 and/or HLA-A*02:06 positive and meeting the threshold for expression of NY-ESO-1 and/or LAGE1a. • Suitable for leukapheresis, including the laboratory parameters mentioned in chapter 5.1.2, item 12 of the protocol. • Time point of leukapheresis the treatment scheme: see chapter 5.1.2, item 13 of the protocol for details. CHEMOTHERAPY/TREATMENT: • Must have received or are receiving at least 1 line of prior systemic therapy. See chapter 5.1.3, item 15 of the protocol for details. • Following treatment with a PD-1/PD-L1 checkpoint blockade therapy administered either as monotherapy or in combination with other checkpoint inhibitors or other therapies, progression is defined by meeting all of the criteria defined in chapter 5.1.3, item 15b of the protocol. • Histologically or cytologically diagnosed unresectable Stage IIIb or Stage IV NSCLC with measurable disease per RECIST v1.1. • Prior radiotherapy: For prior chest radiotherapy see D5a (exclusion criteria) for details. Allowed in case of prior palliative or stereotactic radiosurgery to solitary lesions outside of the chest. • Acceptance of CNS metastases: see chapter 5.1.3, item 19 of the protocol for details. • Acceptance of initiation of the chemotherapy: see chapter 5.1.3, item 20 of the protocol for details. • Acceptance of standard of care line of therapy between leukapheresis and treatment: see chapter 5.1.3, item 21 of the protocol for details. • Contraception guidelines for males and females should be followed, see chapter 5.1.3, item 23 and 5.3.3 of the protocol for details. • Pembrolizumab treatment (rescue) for Arm A: see chapter 5.1.4 of the protocol for details.
Exclusion criteria
Exclusion criteria: SCREENING: • Has received >=3 lines of prior systemic therapy. See protocol section 5.2.1 item 2. • Prior treatment: See protocol section 5.2.1: a. Previous treatment with genetically engineered NY-ESO-1-specific T-cells. b. Previous NY-ESO-1 vaccine or NY-ESO-1 targeting antibody. c. Prior gene therapy using an integrating vector. d. Previous allogeneic hematopoietic stem cell transplant. • Prior malignancy other than NSCLC. Exceptions: see chapter 5.2.1, item 2. • Active autoimmune disease or history. See chapter 5.2.2 item 6,7. • Uncontrolled intercurrent infection, cardiac, pulmonary, demyelinating disease, or unstable liver or biliary disease. See chapter 5.2.2, item 8. • Active infection with HIV, hepatitis B, hepatitis C, EBV, CMV, syphilis, HTLV. See chapter 5.2.2, item 9 of the protocol for details. • QTc >450 msec or QTc >480 msec for patients with BBB. See chapter 5.2.2, item 13 of the protocol for details. LEUKAPHERESIS: • Investigational treatment within 30 days or 5 half-lives (whichever is shorter). See chapter 5.2.2, item 15 of the protocol for details. • Radiotherapy that involves the lung or >25% bone marrow exposure, or mean heart dose >20Gy within 3 months. See chapter 5.2.2, item 19 of the protocol for details. CHEMOTHERAPY/TREATMENT: • Corticosteroids other than inhaled or topical or any other immunosuppressive therapy within 2 weeks. • Live vaccine within 30 days prior to the first dose of study drug. See chapter 5.2.2, table 12 of the protocol for details. • Pembrolizumab treatment (rescue) for Arm A: see chapter 5.2.4 of the protocol for details.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Adverse events, ECOG performance status, Overall Response Rate (ORR) (RECIST 1.1). | — |
Secondary
| Measure | Time frame |
|---|---|
| Progression-Free Survival (PFS). Disease Control Rate (DCR). Duration of Response (DoR). Time to Response (TTR). Pharmacokinetic (PK) parameters. NB: exploratory parameters, see protocol paragraph 3. | — |
Countries
Netherlands
Outcome results
None listed