Master Protocol to Assess the Safety and Recommended Phase 2 Dose of Next Generations of Autologous Enhanced NY-ESO-1/ LAGE-1a TCR Engineered T-cells, alone or in combination with other agents, in Participants with Advanced Tumors (study 209012)

Completed

• Conditions: non small cell lung cancer (NSCLC); synovial sarcoma; myxoid/round cell liposarcoma; 10072990; 10029107

• Registration Number: NL-OMON52650
• Lead Sponsor: GlaxoSmithKline

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 2023-08-18
• Last Update Posted: 15 April 2024

Recruitment & Eligibility

• Status: Completed
• Sex: Not specified
• Target Recruitment: 5

Inclusion Criteria

SUBSTUDY 1:
SCREENING:
• Male or female, age 18 years and above.
• Measurable disease (RESIST v1.1).
• Tumor sample plus report is available for NY-ESO-1 analysis. See protocol
section 6.1.1 item 3.

Synovial sarcoma and myxoid/round cell liposarcoma:
• Diagnosis of synovial sarcoma or myxoid/round cell liposarcoma confirmed by
local histology and with evidence of disease-specific translocation.
• Advanced (metastatic or unresectable) synovial sarcoma or myxoid/round cell
liposarcoma. See protocol section 6.1.1 for details.

NSCLC:
• Histologically or cytologically confirmed Stage IV NSCLC.

LEUKAPHERESIS:
• HLA-A*02:01, HLA-A*02:05 and/or HLA-A*02:06 positive and NY-ESO-1 positive.
See protocol section 6.1.2 item 8-9.
• Measurable disease (RECIST v1.1).
• For sarcoma: Has completed at least one standard of care treatment including
anthracycline
containing regimen OR is intolerant to the therapy. See protocol section 6.1.2,
item 12.
• For NSCLC: Has been previously treated with or is intolerant to PD-1/PD-L1
checkpoint blockade therapy and a platinum-based chemotherapy, or is intolerant
to it. See protocol section 6.1.2, item 13 and 14.
• Left ventricular ejection fraction >=45%. See protocol section 6.1.2 item 15.
• ECOG performance status 0-1.
• Adequate organ function (see protocol Table 9).
• Contraception guidelines for males and females should be followed, see
chapter 6.1.2 item 19 of the protocol for details.
• Negative pregnancy test for female participants able to become pregnant.

TREATMENT:
• Documented radiographic evidence of disease progression from prior line of
therapy.
• A biopsy of non-target tumor tissue obtained within 28 days prior to
initiating the chemotherapy is mandatory. See protocol section 6.1.3 item 23
for details.
For a detailed list of Iclusion Critera, please refer to the protocol for
substudy 1 (page 54-59).

SUBSTUDY 2
SCREENING:
• Male or female, age 18 years and above.
• Tumor sample plus report is available for NY-ESO-1 analysis. See protocol
section 6.1.1 item 3.
• Diagnosis of synovial sarcoma or myxoid/round cell liposarcoma confirmed by
local histology. and with evidence of disease-specific translocation.
• Advanced (metastatic or unresectable) synovial sarcoma or myxoid/round cell
liposarcoma. See protocol section 6.1.1 for details.

LEUKAPHERESIS:
• HLA-A*02:01, HLA-A*02:05 and/or HLA-A*02:06 positive and NY-ESO-1 positive.
See protocol section 6.1.2 item 7.
• Measurable disease (RECIST v1.1).
• Evidence of radiographic or clinical disease progression.
• Has completed at least one standard of care treatment including anthracycline
containing regimen OR is intolerant to the therapy. See protocol section 6.1.2,
item 12.
• Left ventricular ejection fraction >=45%. See protocol section 6.1.2 item 15.
• ECOG performance status 0-1.
• Adequate organ function (see protocol Table 10).
• Contraception guidelines for males and females should be followed, see
chapter 6.1.2 item 18 of the protocol for details.
• Negative pregnancy test for female participants able to become pregnant.

TREATMENT:
• Documented radiographic evidence of disease progression from prior line of
therapy.
• A biopsy of non-target tumor tissue obtained within 28 days prior to
initiating the chemoth

Exclusion Criteria

SUBSTUDY 1:
SCREENING:
• CNS metastases. See protocol section 6.2.2 item 6 for exceptions.
• Clinically significant systemic illness, see protocol section 6.2.1, item 2
for details.
• Previous treatment with genetically engineered NY-ESO-1-specific T cells
NY-ESO-1 vaccine or NY-ESO-1 targeting antibody. See protocol section 6.2.1
item 3.
• Prior gene therapy using an integrating vector. See protocol section 6.2.1
item 4.
• Prior allogeneic hematopoietic stem cell transplant within the last 5 years
or solid organ transplant.

LEUKAPHERESIS:
• CNS metastases. See protocol section 6.2.2 item 6.
• History of chronic or recurrent (within the last year prior to leukapheresis)
severe autoimmune or immune mediated disease requiring steroids or other
immunosuppressive treatments.
• Uncontrolled intercurrent illness. See protocol chapter 6.2.2, item 9 for
details.
• Insufficient pulmonary function with mechanical parameters <40% predicted.
See protocol chapter 6.2.2, item 12 for details
• Current active liver or biliary disease. See protocol chapter 6.2.2, item 11
for details.
• QTc >480 msec. See protocol chapter 6.2.2, item 12 for details.
• Active infections. See protocol chapter 6.2.2, item 14 for details.
• NSCLC: Radiotherapy that involves the lung or bone marrow exposure or heart
exposure. See protocol chapter 6.2.2, item 18 for criteria and other details.

TREATMENT:
• Cytotoxic therapy within the last 3 weeks prior to chemotherapy.
• Systemic corticosteroids or any other immunosuppressive therapy within the
last 2 weeks prior to chemotherapy. See protocol chapter 6.2.3, item 23 for
details.
• >=50 Gy to a significant volume of the pelvis, long bones or
spine. See protocol section 6.2.3 item 20.
• Radiotherapy to the target lesions within the last 3 months. See protocol
chapter 6.2.3, item 24 for details.
• Anti-cancer vaccine within the last 2 months prior to chemotherapy in the
absence of tumor response. See protocol chapter 6.2.3, item 23 for details.
• Live vaccine within the last 4 weeks prior to chemotherapy.
• Immune therapy within the last 4 weeks prior to chemotherapy. See protocol
chapter 6.2.3, item 25 for details.
• Washout periods for prior therapy see protocol chapter 6.2.3, Table 10.
For a detailed list of Exclusion Criteria please refer to the Substudy 1
protocol (Page 60-65).

SUBSTUDY 2:
SCREENING:
• Any other prior malignancy that is not in complete remission. See protocol
section 6.2.1 item 1 for exceptions.
• Clinically significant systemic illness, see protocol section 6.2.1, item 2
for details.
• Previous treatment with genetically engineered NY-ESO-1-specific T cells
NY-ESO-1 vaccine or NY-ESO-1 targeting antibody. See protocol section 6.2.1
item 3.
• Prior gene therapy using an integrating vector. See protocol section 6.2.1
item 4.
• Prior allogeneic hematopoietic stem cell transplant within the last 5 years
or solid organ transplant.

LEUKAPHERESIS:
• CNS metastases.
• History of chronic or recurrent (within the last year prior to leukapheresis)
severe autoimmune or immune mediated disease requiring steroids or other
immunosuppressive treatments.
• Uncontrolled intercurrent illness. See protocol chapter 6.2.2, item 9 for
details.
• Insufficient pulmonary function with mechanical para

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>Dose-limiting toxicities, (serious) adverse events (of special interest).</p><br>

Secondary Outcome Measures

Name	Time	Method
<p>Overall Response Rate (ORR), Duration of Response (DoR). T cell expansion and<br /><br>persistence (peak expansion, Cmax, Tmax, AUC(0-t). Infiltration and phenotype<br /><br>of transduced T cells in the tumor by RNA, DNA and/or protein levels.</p><br>