Presented at Society for Immunotherapy of Cancer, 35th Annual Meeting, Virtual Format, November 9–14, 2020

Safety• All patients experienced at least 1 AE.

– 98% of patients experienced a Grade ≥3 event, which were most commonly hematologic in nature (Table 4).

• All patients in Cohorts 1–3 and 87% of patients in Cohort 4 experienced multiple cytopenias (Table 4).– One patient in Cohort 2 experienced a fatal cytopenia due to bone marrow failure,

approximately 3 months after lete-cel infusion. The investigator assessed bone marrow hypocellularity to be probably related to lymphodepletion.

– All other cytopenia events were of maximum Grade 3 or 4.• Twenty-two events of cytokine release syndrome (CRS, an AESI) were experienced by

20/45 (44%) patients.– For patients with CRS, Grade 1 events occurred in 9/20 (45%) patients, Grade

2 (n=7/20; 35%), Grade 3 (n=3/20, 15%), and Grade 4 (n=1/20, 5%); CRS was classified as an SAE in 5/20 (25%) of patients (SAE Grade ≥3 in 2/20 [10%] patients).

– The incidence of CRS across cohorts was 42%, 54%, 60%, and 33% in Cohorts 1, 2, 3, and 4 respectively.

– Median time of onset was 5 days. For 90% of patients (18/20), onset was between 1 and 14 days.

– Four patients were treated with tocilizumab due to CRS.• Two patients in Cohort 2 experienced Grade 3 Guillain-Barré syndrome (an AESI)

considered serious in both reports. – Both patients were treated with intravenous immunoglobulin with improvement in

their symptoms.– In one patient, the event was considered resolved approximately 4 weeks after the

onset of symptoms.– In the second patient, the investigator reported normal function and return to

independence, at the 9-month follow-up visit.• There were no events of immune effector cell-associated neurotoxicity syndrome

previously known as encephalopathy syndrome (an AESI).• No patients tested positive for replication-competent lentivirus.

D’Angelo SP1, Demetri GD2, Van Tine BA3, Druta M4, Glod J5, Chow W6, Hasan AN7, Chiou VL7, Tress J7*, Edwards J8, Young T7, Woessner M7, Gyurdieva A7, Zajic S7, Goodison S7, Araujo D9

1Memorial Sloan Kettering Cancer Center, New York, NY, USA; 2Dana-Farber Cancer Institute and Ludwig Center at Harvard, Boston, MA, USA; 3Washington University in St. Louis, St. Louis, MO, USA; 4H. Lee Moffitt Cancer Center, Tampa, FL, USA; 5National Cancer Institute, Bethesda, MD, USA; 6City of Hope Comprehensive Cancer Center, Duarte, CA, USA; 7GlaxoSmithKline, Collegeville, PA, USA; 8GlaxoSmithKline, Stockley Park, Middlesex, UK; 9University of Texas/MD Anderson Cancer Center, Houston, TX, USA; At time of study

Final analysis of the Phase 1 trial of NY-ESO-1–specific T-cell receptor (TCR) T-cell therapy (letetresgene autoleucel; GSK3377794) in patients with advanced synovial sarcoma (SS)Poster number: 298

• Patients with advanced (recurrent or metastatic) synovial sarcoma (SS) have a poor prognosis and limited treatment options.1,2

– Systemic agents including anthracyclines, ifosfamide, trabectedin, or pazopanib can occasionally induce transient responses or stabilize disease1

but more effective treatments are needed.– Efficacy outcomes with chemotherapy are poor in both the first- and second-

line (2L) setting, with low response rates and limited overall survival (OS).3

• New York esophageal squamous cell carcinoma 1 (NY-ESO-1) is an intracellular protein of the cancer/testis antigen family of tumor-associated antigens that is expressed in over 75% of SS tumors.4

– The t(X;18)(p11;q11) translocation commonly found in SS and known to alter chromatin remodeling may be responsible for aberrant expression of NY-ESO-1 in SS.5

• Letetresgene autoleucel (lete-cel; GSK3377794) consists of autologous CD4+ and CD8+ T cells that have been genetically modified to express a T-cell receptor (TCR) recognizing NY-ESO-1 bound to human leukocyte antigen A*02 (HLA-A*02) to induce anti-tumor responses in patients with SS (Figure 1).

• Study NCT01343043 (GSK 208466) is a Phase I clinical trial assessing the efficacy and safety of lete-cel and various lymphodepletion regimens in 4 cohorts of patients with previously treated advanced SS; preliminary clinical data were previously reported.6,7

Background

Aim

Results

MethodsConclusions

• To report the final analysis of the efficacy and safety of lete-cel in Cohorts 1–4 in study NCT01343043.

Study design• This study expanded from a single-cohort, single-arm, non-randomized, open-

label, pilot study (Cohort 1) to include 3 additional patient cohorts (Cohorts 2, 3, 4) differentiated by tumor expression of NY-ESO-1 antigen and lymphodepletion regimens prior to T-cell infusion (Table 1).

• Patients underwent lymphodepletion with a high or low dose of cyclophosphamide, with or without fludarabine, according to cohort (Figure 2).

Table 1. Antigen expression and lymphodepleting regimen for each cohort

NY-ESO-1 expression Lymphodepletion regimen

Cohort 1 n=12

HIGHIHC score 2+ or 3+ in ≥50% of tumor cells

HIGH doses of fludarabine and cyclophosphamideFludarabine 30 mg/m2 IV on Days –5 to –2 Cyclophosphamide 1800 mg/m2 IV on Days –3 and –2

Cohort 2 n=13

LOWIHC score ≥1+ in ≥1% cells but not exceeding 2+ or 3+ in ≥50% cells

HIGH doses of fludarabine and cyclophosphamideFludarabine 30 mg/m2 IV on Days –5 to –2 Cyclophosphamide 1800 mg/m2 IV on Days –3 and –2

Cohort 3 n=5

HIGHIHC score 2+ or 3+ in ≥50% of tumor cells

HIGH dose of cyclophosphamide onlyCyclophosphamide 1800 mg/m2 IV on Days –3 and –2

Cohort 4 n=15

HIGHIHC score 2+ or 3+ in ≥50% of tumor cells

LOW doses of fludarabine and cyclophosphamideFludarabine 30 mg/m2 IV on Days –7 to –5 Cyclophosphamide 600 mg/m2 IV on Days –7 to –5

IHC, immunohistochemistry; IV, intravenous; NY-ESO-1, New York esophageal squamous cell carcinoma 1.

Table 2. Patient baseline demographics and clinical characteristicsa

Parameter Cohort 1

(n=12)Cohort 2

(n=13)Cohort 3

(n=5)Cohort 4

(n=15)Overallb

(N=45)Sex, n (%)

Men 6 (50) 7 (54) 3 (60) 8 (53) 24 (53)Women 6 (50) 6 (46) 2 (40) 7 (47) 24 (47)

Median age (range), yc 30 (18–50)

29 (11–73)

25 (15–39)

36 (20–69)

32 (11–73)

Race, n (%)Black/African American 0 0 1 (20) 1 (7) 2 (4)White 11 (92) 10 (77) 4 (80) 14 (93) 39 (87)Other 1 (8) 3 (23) 0 0 4 (9)

HLA-A status, n (%)HLA-A*02:01 10 (83) 13 (100) 5 (100) 14 (93) 42 (93)HLA-A*02:05 0 0 0 1 (7) 1 (2)HLA-A*02:06 1 (8) 0 0 0 1 (2)Otherd 1 (8) 0 0 0 1 (2)

NY-ESO-1 status, n (%)Positive highe 12 (100)f 0 5 (100) 15 (100) 32 (71)Positive lowg 0 13 (100) 0 0 13 (29)

Disease stage at enrollment, n (%)Stage Ih 0 1 (8) 0 1 (7) 2 (4)Stage III 0 0 0 1 (7) 1 (2)Stage IV 9 (75) 10 (77) 3 (60) 9 (60) 31 (69)Other 3 (25) 2 (15) 2 (40) 4 (27) 11 (24)

ECOG performance status, n (%)i

0 7 (58) 6 (46) 4 (80) 8 (53) 25 (56)1 5 (42) 6 (46) 1 (20) 7 (47) 19 (42)

Prior systemic therapy, n (%) 12 (100) 13 (100) 5 (100) 15 (100) 45 (100)Type of systemic therapy, n (%) 12(100) 13 (100) 5 (100) 15 (100) 45 (100)

Chemotherapy 1(8) 0 0 1 (7) 2 (4)Immunotherapy 0 0 0 2 (13) 2 (4)Vaccine 0 1 (8) 0 1 (7) 2 (4)Other 12(100) 13 (100) 5 (100) 15 (100) 45 (100)

Bridging therapy, n (%)Yes 0 8 (62) 2 (40) 5 (33) 15 (33)No 12 (100) 5 (39) 3 (60) 10 (67) 30 (67)

ECOG, Eastern Cooperative Oncology Group; HLA, human leukocyte antigen; IHC, immunohistochemistry; NY-ESO-1, New York esophageal squamous cell carcinoma 1. aTotals may not sum to 100% due to rounding. bOverall column gives sum of all cohorts unless otherwise specified. cAt informed consent. dResult was ambiguous and assumed to be HLA 02:01 positive at >99.99% probability. eIHC score 2+ or 3+ in ≥50% of tumor cells. fOne patient had only >30% cells at 3+, which was defined as positive expression (≥3+ in 25% of cells) in the protocol amendment under which the patient was enrolled. gIHC score ≥1+ in ≥1% cells but not exceeding 2+ or 3+ in ≥50% cells. hStage I patients may have been described as Stage I at diagnosis rather than enrollment. iOne subject in Cohort 2 had an ECOG status of 1 at screening but was a status 2 at the time of baseline. Eligibility did not specify subjects must meet ECOG at screening and baseline.

• Final results from this Phase I study showed that lete-cel infusion following lymphodepletion chemotherapy has persistent clinically meaningful activity with a manageable safety profile in patients with previously treated advanced SS.

• A single lete-cel infusion resulted in deep responses that were durable in a subset of patients, and showed encouraging overall survival in responding patients. A complete response was achieved in one patient.

• Although patient numbers were small, ORRs compared favorably to approved therapies in this setting. – Responses were observed in all cohorts, but the highest response and longest OS observed in Cohort 1 suggest that patients with high

NY-ESO-1 expression who received a more intensive lymphodepletion regimen may receive the greatest benefit.• Lete-cel clinical efficacy and safety is being further evaluated in both previously-treated and treatment-naïve SS, as part of the IGNYTE-ESO

master protocol study (NCT03967223), which is currently enrolling.

Key patient eligibility criteria• Inclusion criteria:

– Age ≥4 years – Histologically confirmed advanced SS that was unresectable

and/or metastatic, and not actively responding or intolerant to standard chemotherapy with ifosfamide and/or doxorubicin

– Confirmed tumor expression of NY-ESO-1 antigen by immunohistochemistry – HLA-A*02:01, HLA-A*02:05, and/or HLA-A*02:06 alleles by high resolution testing

– Measurable disease to allow for assessment of anti-tumor response– Eastern Cooperative Oncology Group (ECOG) performance status of 0–1

• Exclusion criteria:– Untreated central nervous system metastasis– Prior treatment with genetically engineered NY-ESO-1 specific T cells– Clinically significant systemic illness– Active HIV, hepatitis B or C or human T-lymphocyte infection 1 or 2

Endpoints and assessment• The primary efficacy outcome was investigator-assessed overall response

rate (ORR; complete response [CR] or partial response [PR]) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.

• Additional efficacy outcomes included duration of response (DoR), progression-free survival (PFS), and OS.

• Transduced cell persistence was measured by quantitative polymerase chain reaction of transgene vector copies in DNA extracted from peripheral blood mononuclear cells.

• Safety was monitored throughout with the reporting of adverse events (AEs), serious AEs (SAEs) and AEs of special interest (AESI), evaluated using Common Terminology Criteria for Adverse Events v4.0 (CTCAE v4.0).

Statistical analysis• The intent-to-treat (ITT) population included all enrolled patients; safety and

efficacy were assessed in patients who received lete-cel infusion (modified ITT [mITT] population).

• The study was neither designed nor powered for statistical comparisons between cohorts.

• OS data are reported from a separate long-term follow-up protocol (Figure 2); the data cut-off for this analysis was January 27, 2020.

Cancer

cell

Lete-cel(NY-ESO-1 autologous

T cell)

TCR

HLA-A*02:01,*02:05, or *02:06

NY-ESO-1peptide

Cancercell

Lete-cel

Tumor

T cell

Figure 1. Lete-cel mode of action

HLA, human leukocyte antigen; lete-cel, letetresgene autoleucel; NY-ESO-1, New York esophageal squamous cell carcinoma 1; TCR, T-cell receptor.

PART 1 –Screening

PART 2 – Leukapheresis& Manufacture

Long-termFollow-up

Study 208750(NCT03967223)

PART 3 – Lymphodepletion, Treatment

& Follow-up

Leukapheresiseligibility

screening28 daysbefore

apheresisHLA-A*02 NY-ESO-1

TreatmenteligibilityconfirmedDays −13

to −8

Long-term follow-up

Up to 15 yearsafter

lete-cel

Lympho-depletionDays −7

to −2

Lete-celinfusion

Day 0

Target dose:0.125×109 (<40 kg) or

5×109

(≥40 kg)transduced

cells/kg

Follow-updisease

assessmentWeeks 4, 8,

12, and every3 months till

Year 2,then yearlytill Year 5

Leukapheresis

Manufacture oflete-cel 42 days

• Toxicity• Anti-tumoreffects

• Immuneendpoints

• Enrichment forCD3+ T cells

• Activation andtransductionof CD3+ T cells withNY-ESO-1 TCR

• T-cell expansion• Harvesting, bead

removal, and formulation

Figure 2. Study design

CD3, cluster of differentiation 3; HLA, human leukocyte antigen; lete-cel, letetresgene autoleucel; NY-ESO-1, New York esophageal squamous cell carcinoma 1; TCR, T-cell receptor.

Cohort 1a

8.4

–4.8–15.5 –15.8

–26.4

–50.0 –54.5 –54.8–64.1 –65.6 –70.8

–100.0

Progressive diseaseConfirmed complete or partial responseStable disease

60

40

20

0

–20

–40

–60

–80

–100

–120

Cha

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)

Cohort 2b

41.7

2.5

–5.2–13.3 –14.4

–28.6 –31.3 –31.6–42.1 –44.0

–50.9 –51.5

60

40

20

0

–20

–40

–60

–80

–100

–120

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Cohort 3b

5.7

–77.8

–23.5

–8.6

60

40

20

0

–20

–40

–60

–80

–100

–120

Cha

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Cohort 450.6

13.01.2

–3.3–13.6–14.5–16.7–19.4–24.3–26.5

–47.8–38.7–55.0–58.7

–77.3

60

40

20

0

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Figure 3. Maximal percentage reduction in sum of diameters of target lesions (investigator-assessed) from baseline through progression or prior to subsequent anti-cancer therapy (mITT population)

Best overall response recorded from the time of first T-cell infusion until disease progression. If patients had an unconfirmed complete or partial response, then the best overall response was considered to be stable disease. aPatient in Cohort 1 had a PR at Week 4, PD at Week 8. There was no confirmed response so best overall response was recorded as PD. bOne patient in each cohort was not evaluable for response. mITT, modified intent-to-treat.

Patient population and study agent exposure• Of a total of 50 patients enrolled (ITT population), 5 did not receive lete-cel,

therefore 45 patients made up the mITT population. • Baseline patient characteristics were similar across cohorts; roughly half of

patients were men, median age was 32 years, and most patients (69%) had stage IV disease at enrollment (Table 2).

• Median time on study was 480, 278, 605, and 643 days in Cohorts 1, 2, 3, and 4, respectively.

Efficacy and lete-cel persistence (Cmax)• Among the cohorts, ORR ranged from 20% in Cohort 3 to 50% in Cohort 1

(Table 3).– Cohort 1 included the only CR recorded after a single lete-cel infusion, which

lasted for 34 weeks; 14 PR were observed across cohorts (Figure 3; Figure 4).• Median DoR ranged from 8.6 weeks in Cohort 2 to 32.1 weeks in Cohort 3

(Table 3).• Median PFS across cohorts ranged from 8.6 weeks in Cohort 3 to 22.4 weeks in

Cohort 4 (Table 3). • Median OS was 24.3, 9.9, and 19.9 months in Cohorts 1, 2, and 3, respectively;

OS data for Cohort 4 were not mature at the time of analysis (Table 3).– At study completion, 2 patients in Cohort 1, 1 patient in Cohort 3, and 3

patients in Cohort 4 remain in long-term follow-up under a separate protocol.• Responders (CR/PR) generally had a higher peak persistence (Cmax) of lete-cel

compared with non-responders (stable disease/progressive disease; Table 3).– Time to peak persistence (Cmax) was similar across cohorts and in responders

(8 days; 95% confidence interval [CI]: 4–29) vs non-responders (8 days; 95% CI: 4–353).

DisclosuresSPD’A reports paid consultancy for Amgen, EMD Serono, GSK, Immune Design, Immunocore, Incyte, and Nektar; research support from Bristol-Myers Squibb, Deciphera, and Merck; and other financial/material support from Adaptimmune. GDD declares scientific consultancy with research funding to Dana-Farber from AbbVie, Adaptimmune, Bayer, Daiichi Sankyo, Epizyme, GSK, Ignyta, Janssen, LOXO Oncology, Mirati, Novartis, Pfizer, PharmaMar, Roche/Genentech, and ZioPharm; paid consultancy for GSK, EMD-Serono, ICON plc, MEDSCAPE, MJ Hennessey/OncLive, Polaris Pharmaceuticals, Sanofi, and WCG/Arsenal Capital; consultancy/scientific advisory board membership with minor equity holding for Bessor Pharmaceuticals, Caprion/HistoGeneX, Caris Life Sciences, Champions Biotechnology, Erasca Pharmaceuticals, G1 Therapeutics, and RELAY Therapeutic; board membership and scientific advisory board consultancy with minor equity holding for Blueprint Medicines, Merrimack Pharmaceuticals (ended Oct 2019), and Translate BIO; royalties from Novartis to institute (Dana-Farber) for use of patent of imatinib in GIST; and nonfinancial interests in AACR Science Policy and Government Affairs Committee Chair, Alexandria Summit, and McCann Health. BAVT holds board membership/committee appointment for Polaris; declares paid consultancy for Adaptimmune, Caris, CytRx, Daiichi Sankyo, Deciphera, Epizyme, Immune Design, Janssen, Lilly, Novartis, and Pfizer; speakers bureau/paid presentations for Adaptimmune, Caris, GSK, Janssen, Lilly, and Novartis; research funding from GSK, Merck, Pfizer, and Tracon; and travel support from GSK. MD declares honoraria from Adaptimmune, Blueprint, Daiichi Sankyo, Deciphera, and Epizyme. JG and DA have nothing to disclose. WC declares paid consultancy for GSK and other financial/material support from AdvenChen. ANH is an employee of and holds stock/stock options in GSK and receives royalties from Atara Biotherapeutics. VLC, JE, TY, MW, SZ, and SG are employees of and hold stock/stock options in GSK. JT is a former employee of GSK and holds stock/stock options in GSK. AG is an employee of GSK and holds stock/stock options in GSK and Amgen.

AcknowledgmentsWe thank all patients and their families for participation in this study. We thank Ran Ji for contributions to statistical analysis. Medical writing assistance was provided by Sharon Bryant, DPT, of Fishawack Indicia Ltd, UK, and funded by GSK. This study (208466) was funded by GlaxoSmithKline (GSK) and Adaptimmune.

Ethical approvalThis study was approved by the appropriate institutional review boards and independent ethics committees.

References1. Corey RM, et al. Cancer Med 2014;3(5):1404–15.2. Desar IME, et al. Curr Treat Options Oncol 2018;19:13.3. Minchom A, et al. Sarcoma 2010;264360.4. Lai JP, et al. Mod Pathol 2012;25(6):854–8. 5. Thomas R, et al. Front Immunol 2018;9:947.6. D’Angelo SP, et al. Cancer Discov 2018;8(8):944–57.

7. D’Angelo SP, et al. Presented at the Society for Immunotherapy of Cancer Congress, National Harbor, MD; November 6–10, 2019.

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or via tago.ca/sitc1.

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Presenting author email: dangelos@mskcc.org

Please find an online version of the plain language summary to accompany this publication

by scanning the QR code or via tago.ca/sitc5.

Table 4. Number of patients with Grade ≥3 AEs in the mITT populationa

Parameter Cohort 1

(n=12)Cohort 2

(n=13)Cohort 3

(n=5)Cohort 4

n=15Patients with any Grade ≥3 AE 12 (100) 13 (100) 5 (100) 14 (93)

Grade ≥3 AE in ≥25% of patients in any cohortLeukopeniab 11 (92) 12 (92) 5 (100) 11 (73)Neutropeniab 10 (83) 11 (85) 4 (80) 10 (67)Anemiab 10 (83) 11 (85) 3 (60) 7 (47)Thrombocytopeniab 8 (67) 11 (85) 4 (80) 7 (47)Lymphopeniab 12 (100) 8 (62) 3 (60) 6 (40)Hypophosphatemia 9 (75) 5 (39) 2 (40) 3 (20)Febrile neutropenia 4 (33) 4 (31) 0 6 (40)Dyspnea 1 (8) 3 (23) 3 (60) 0Hyponatremia 3 (25) 3 (23) 1 (20) 0

Patients with any serious Grade ≥3 AE 5 (42) 5 (38) 3 (60) 4 (27)

Serious Grade ≥3 AE in ≥3 patients Febrile neutropenia 2 (17) 1 (8) 0 2 (13)Dyspnea 1 (8) 1 (8) 1 (20) 0Neutropeniab 1 (8) 2 (15) 0 0

AE, adverse event; mITT, modified intent-to-treat.aFrom start date of lymphodepletion through end of study. bSynonymous preferred terms are combined (leukopenia and white blood cell decreased; neutropenia and neutrophil count decreased; anemia and red blood cell count decreased; thrombocytopenia and platelet count decreased; and lymphopenia and lymphocyte count decreased).

Table 3. Lete-cel dose, efficacy and peak persistence (Cmax) in responders and non-responders (mITT population)

Parameter Cohort 1

(n=12)Cohort 2

(n=13)Cohort 3

(n=5)Cohort 4

n=15

Median (range) transduced cell dose (x109)

3.60 (0.45–14.36)

2.42 (1.60–5.01)

3.02 (1.53–5.00)

2.40 (1.00–4.95)

Efficacy, n (%)

Overall response ratea (95% CI)

6 (50)(0.21–0.79)

4 (31)(0.09–0.61)

1 (20)(0.01–0.72)

4 (27)(0.08–0.55)

Best overall responseb

Complete response 1 (8) 0 0 0

Partial response 5 (42) 4 (31) 1 (20) 4 (27)

Stable disease 5 (42) 7 (54) 3 (60) 10 (67)

Progressive disease 1 (8) 1 (8) 0 1 (7)

Not evaluable 0 1 (8) 1 (20) 0

Median DoR (range), weeks 31.0(13–72)

8.6(8–13)

32.1(32–32)

16.4(14–94)

Median PFS (95% CI), weeks 15.4 (7.7–38.0)

13.1 (7.9–13.9)

8.6 (0.7–36.1)

22.4 (11.3–26.6)

Median OS (95% CI), monthsc 24.3 (8.5–48.8)

9.9(3.9–19.6)

19.9 (8.8–NA)

Not mature; to be reported

later

Peak persistence, median (range), DNA copies/µg

Respondersd106,174(76,185–192,445)

65,875(13,365–197,546)

123,314(123,314–123,314)

40,137(5677–

131,176)

Non-responderse30,601

(11,265–119,883)

72,564(22,627–145,791)

15,688(9453– 43,015)

19,650(164–

111,260)

CI, confidence interval; CR, complete response; DoR, duration of response; lete-cel, letetresgene autoleucel; mITT, modified intent-to-treat; NA, not available; OS, overall survival; PD; progressive disease; PFS, progression-free survival; PR, partial response; SD, stable disease.aProportion of patients with a confirmed CR or PR relative to total number of patients. bRecorded from the time of first T-cell infusion until disease progression. cData from Long-Term Follow-up Study, cut-off January 27, 2020. dPatients with CR/PR. ePatients with PD/SD.

Cohort 1Responder (n=6)

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200 400 600

Non-Responder (n=6)Cohort 2

Responder (n=4)

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Non-Responder (n=8)

Cohort 3Responder (n=1)

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0 200 400 600 200 400 6000Days Days

Non-Responder (n=4)Cohort 4

Responder (n=4)50

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Non-Responder (n=11)

Figure 4. Change from baseline in target lesion through progression and prior to surgical resection over time by response statusa (mITT Population, investigator-assessed)

aResponders include patients with complete/partial response, non-responders includes patients with stable/progressive disease. mITT, modified intent-to-treat.