A study of NY-ESO-1 T-cells (GSK3377794) alone and in combination with Pembrolizumab in NSCLC patients.
- Conditions
- Stage IIIb or Stage IV Non-Small Cell Lung Cancer (NSCLC)MedDRA version: 21.1Level: PTClassification code 10061873Term: Non-small cell lung cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2018-003949-42-GB
- Lead Sponsor
- GlaxoSmithKline Research & Development Ltd
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 53
Part 1 (Screening) begins with HLA allele genotyping and tumor antigen expression for
patients with histologically or cytologically confirmed advanced Stage IIIb or IV or
recurrent NSCLC.
1. The participant (or legally acceptable representative if applicable) provides written
informed consent for the screening process described as Target Antigen Expression
Screening” in the SoA (Section 1.3).
2. The participant has successfully completed the HLA and target expression evaluations.
- Participant is positive for any of the following alleles: HLA-A*02:01, HLA-A*02:05, and HLA-A*02:06.
- Participant’s tumor (archival specimen) has been reviewed by the GSK designated
laboratory and confirmed as meeting the pre-defined threshold for expression of NY-ESO-1 and/or, if tested, LAGE-1a.
After HLA allele genotyping and tumor antigen expression have been found positive, an
eligible participant must fulfill all of the following inclusion criteria:
3. The participant (or legally acceptable representative if applicable) provides written
informed consent for the trial.
4. Age =18 years on the day of signing informed consent.
5. Pending approval of Medical Monitor (or designee), participants can be enrolled in
other experimental interventional clinical studies during the screening and leukapheresis stages of this study (GSK208471). (refer to exclusion criteria #19, 20, 22)
6. Histologically or cytologically diagnosed unresectable Stage IIIb or Stage IV NSCLC with measurable disease per RECIST v1.1 as assessed by local site investigator/radiology.
Note: Lesions situated in a previously irradiated area are considered measurable if
progression has been demonstrated in such lesions.
a. Arms A and B: Participants with NSCLC with WT EGFR and WT ALK/ROS1 based on SoC diagnostic test.b. Arm C: Participants with NSCLC with EGFR or ALK/ROS1 aberration based on SoC diagnostic test.
7. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.
8. Predicted life expectancy that is =3 months.
9. Participant has left ventricular ejection fraction =50% or as per institution’s
guidelines.
10. Adequate venous access for leukapheresis.
11. In the Investigator’s opinion, the participant is fit for lymphodepleting chemotherapy
and infusion of GSK3377794.
An archived biopsy of the tumor tissue obtained at any time from the initial diagnosis of
NSCLC to time of study entry is mandatory for tumor antigen expression analysis (NY-ESO-1 and, when available, LAGE-1a).
Note: Based upon approval of the Medical Monitor (or designee), participants can be
enrolled in other experimental interventional clinical studies during the screening and
leukapheresis stages of this study.
5.1.2. Leukapheresis (Part 2)
All screening criteria described in Section 5.1.1 must be reviewed and fulfilled along
with all the following criteria prior to leukapheresis.
12. In the Investigator’s opinion, the participant is suitable for leukapheresis, including
the following laboratory parameters being above the thresholds in the table on page 54 of the Protocol.
13. Leukapheresis can be collected as follows:
a. Between lines of therapies.
b. After the first 3 cycles of current systemic chemotherapy
c. During PD-1/PD-L1 checkpoint blockade regimen (alone or in combination with
chemotherapy) after the first 3 cycles of checkpoint blockade therapy. Wash-out for anti-PD-1/ PD-L1 monotherapy is NOT required.
d. After 9 weeks of current TKI therapy
e. After
1. NSCLC with BRAF, HER2, and/or any other actionable genetic aberration that can be treated with targeted standard of care (NCCN recommended) therapy.
2. Prior therapies:
a. Arm A and B: Has received and failed =3 lines of systemic therapy. Participants who are receiving a second line of systemic therapy during the study screening period can be eligible if they have an expected time to progression of at least four months per investigator assessment, a positive benefit-risk evaluation is provided by the investigator, and there is agreement with the Sponsor Medical Monitor or designee (all parameters are necessary).
b. Arm C: Has received =4 lines of systemic therapy (except for the below exclusion criterion #2c).
c. Arm C: Participants with NSCLC with EGFR or ALK/ROS1 aberration who are receiving a fourth line of systemic therapy during the study screening period can be eligible if all the following parameters apply:
- Have an expected time to progression of at least four months per
investigator assessment
- A positive benefit-risk evaluation is provided by the investigator
- In agreement with the Sponsor Medical Monitor (or designee)
3. Prior treatment:
a. Any prior treatment with oncology cell therapy (TCR T-cell therapy or CAR-T therapy)
b. Prior gene therapy using an integrating vector
c. Docetaxel therapy after having failed either doublet platinum-based chemotherapy or PD-1/PD-L1 checkpoint blockade therapy
4. Symptomatic or untreated leptomeningeal or brain metastases or spinal cord
compression. Prior malignancy other than NSCLC, with the following exceptions:
a. Participants with a history of completely resected non-melanoma skin cancer or successfully treated in situ carcinoma are eligible.
b. Participants with malignancies that have been definitively treated may be eligible for the study based on consultation between the Investigator and Sponsor Medical Monitor (or designee).
6. Participant has a history of allergic reactions attributed to compounds of similar
chemical or biologic composition to cyclophosphamide, fludarabine, or other agents
used in the study (participants with vitiligo or resolved childhood asthma/atopy are
an exception to this rule).
7. Has severe hypersensitivity (= Grade 3) to pembrolizumab and/or any of its
excipients.
8. Has an active autoimmune disease that has required systemic treatment in past
2 years (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment and is allowed.
9. Participant has a history of chronic or recurrent (within the last year prior to enrollment) severe autoimmune or active immune-mediated disease requiring steroids or other immunosuppressive treatments.
10. Prior allogeneic/autologous bone marrow or solid organ transplantation (participants
who have had a transplant 5 or more years ago, are eligible as long as there are no
symptoms of GVHD) or prior allogeneic hematopoietic stem cell transplantation within the last 5 years.
11. Uncontrolled intercurrent illness including, but not limited to:
a. Ongoing or active infection
b. Clinically significant cardiac disease defined by congestive heart failure New York Heart Association (NYHA) Class >1
c. Uncontrolled clinically significant arrhythmia in last 6 months
d. Acute coronary syndrome (angina or myocardial
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method