| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Locally Advanced, Unresectable, PD L1 Selected Non- Small Cell Lung Cancer Where Disease Has Not Progressed After Concurrent Chemoradiotherapy |
|
| E.1.1.1 | Medical condition in easily understood language |
| Non-Small Cell Lung Cancer |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 21.1 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10061873 |
| E.1.2 | Term | Non-small cell lung cancer |
| E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
• Compare progression-free survival (PFS) as assessed by the
Independent Review Committee (IRC) per Response Evaluation Criteria
in Solid Tumors (RECIST) Version (v) 1.1 in ociperlimab plus tislelizumab
(Arm A) versus Durvalumab (Arm C) among patients with locally
advanced non-small cell lung cancer (LA NSCLC) whose disease has not
progressed after concurrent chemoradiotherapy (cCRT) and with PD-L1
≥ 50%
• Compare PFS as assessed by the IRC per RECIST v1.1 in ociperlimab
plus tislelizumab (Arm A) versus Durvalumab (Arm C) among patients
with LA NSCLC whose disease has not progressed after cCRT and with
PD-L1 ≥ 1% |
|
| E.2.2 | Secondary objectives of the trial |
• Compare overall survival (OS) in Arm A versus Arm C among patients
(pts) with PD-L1 ≥ 50%
• Compare OS in Arm A versus Arm C among pts with PD-L1 ≥ 1%
• Evaluate overall response rate (ORR) and duration of response (DOR)
in Arm A versus Arm C among pts with PD-L1 ≥ 50% and ≥ 1%
• Evaluate time to death or distant metastasis (TTDM) in Arm A versus
Arm C among pts with PD-L1 ≥ 50% and ≥ 1%
• Compare PFS2 in Arm A versus Arm C among pts with PD-L1 ≥ 50%
and ≥ 1%
• Evaluate safety and tolerability in 3 treatment arms among pts with
PD-L1 ≥ 50% and ≥ 1%
• Compare impact of treatments on pt health related quality of life
(HRQoL) in Arm A versus Arm C among pts with PD-L1 ≥ 50% and ≥ 1%
• Characterize the pharmacokinetics (PK) of ociperlimab and
tislelizumab
• Assess host immunogenicity to ociperlimab and tislelizumab
• Evaluate association of PD-L1 and TIGIT expression with clinical
efficacy to ociperlimab plus tislelizumab or tislelizumab or durvalumab only |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Age ≥ 18 years on the day of signing the ICF (or the legal age of
consent in the jurisdiction in which the study is taking place).
2. Ability to provide written informed consent and to understand and
agree to comply with the requirements of the study and the schedule of
assessments.
3. Patient has histologically or cytologically confirmed, locally advanced,
unresectable Stage III NSCLC (AJCC Cancer Staging Manual 2017,
derived from IASLC) prior to initiation of cCRT.
4. Patients must have completed at least 2 cycles of platinum-based
chemotherapy concurrent with radiotherapy. For patients who are
recovering from toxicities associated with prior treatment, the first dose
of study treatment may be delayed by up to 42 days from the end of the
cCRT. It is recommended to screen the patients within 14 days after the
completion of cCRT.
a. The platinum-based chemotherapy regimen must contain cisplatin or
carboplatin, and may contain one of the following agents: etoposide,
vinblastine, vinorelbine, taxane (paclitaxel or docetaxel), or pemetrexed,
according to the local standard of care regimens. If a patient was
receiving a weekly chemotherapy regimen, platinum-based
chemotherapy of at least 4 weeks should be completed.
b. The last dose of chemotherapy must be administered no later than the
last dose of radiotherapy. Consolidation chemotherapy is not allowed
after radiotherapy; but induction chemotherapy no more than 2 cycles
before cCRT is allowed.
c. Where possible, chemotherapy regimens should be given according to
National Comprehensive Cancer Network (NCCN) Guidelines, European
Society for Medical Oncology (ESMO) Guidelines, Chinese Society of
Clinical Oncology (CSCO) Guidelines, Japan Lung Cancer Society (JLCS)
Guidelines, or other local guidelines if applicable.
d. Patients must have received a total dose of radiation of 60 ± 10% Gy
(54 to 66 Gy), as part of the CRT.
e. The minimum technical standard for radiotherapy is 3D conformal
radiotherapy (3D CRT) with CT planning. Intensity modulated
radiotherapy (IMRT) is recommended.
f. RT dose received by organs is recommended to be (the medical
monitor needs to be consulted to confirm eligibility for the patients who
received higher RT dose for the organs below):
• Spinal cord: max dose ≤ 48 Gy
• Lung: V20 ≤ 35%, mean dose ≤ 20 Gy
• Esophagus: mean dose ≤ 34Gy
• Heart: V50 ≤ 25%, mean dose ≤ 20 Gy
5. Patients must have not experienced PD following definitive, platinum
based cCRT.
6. Agree to provide archival tissue (formalin-fixed paraffin-embedded
block containing tumor [preferred] or approximately 6 to 15 freshly cut
unstained slides) or fresh biopsy obtained prior to cCRT (if archival
tissue is not available) for prospective central evaluation of PD-L1 levels
and retrospective analysis of other biomarkers. PD-L1 status will be
assessed centrally in either a previously obtained archival tumor tissue
or fresh tissue obtained from a biopsy collected prior to the first dose of
cCRT via VENTANA PD L1 (SP263) assay. Only patients with PD L1 ≥ 1%
of TC are eligible.
7. ECOG Performance Status of 0 or 1.
8. Patients must have adequate organ function as indicated by the following screening laboratory values obtained within 7 days before
randomization:
a. Patients must not have required blood transfusion or growth factor
support ≤ 14 days before sample collection at screening for the
following:
i. Absolute neutrophil count (ANC) ≥ 1.5 x 109/L
ii. Platelets ≥ 75 x 109/L
iii. Hemoglobin ≥ 90 g/L or ≥ 5.6 mmol /L (Note: Criteria must be met
without a transfusion within 14 days of obtaining the sample)
b. Serum creatinine ≤ 1.5 x upper limit of normal (ULN), or for patients
whose serum creatinine > 1.5×ULN, estimated Glomerular Filtration Rate
(GFR) by Chronic Kidney Disease Epidemiology Collaboration (CKD EPI)
equation or Calculated creatinine clearance (CrCl) by Cockcroft Gault
(CG) equation ≥ 30 mL/min.
c. Serum total bilirubin ≤ 1.5 x ULN (total bilirubin must be < 3 x ULN for
patients with Gilbert syndrome).
d. Aspartate aminotransferase (AST) and alanine aminotransferase
(ALT) ≤ 2.5 x ULN.
e. INR and aPPT ≤ 1.5 x ULN. This applies only to patients who are not
receiving therapeutic anticoagulation; patients receiving therapeutic
anticoagulation should be on a stable dose.
[Further inclusion criteria, relating to contraception, can be found in the
protocol.] |
|
| E.4 | Principal exclusion criteria |
1. Prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, TIGIT, or any
other antibody or drugs specifically targeting T-cell co-stimulation or
checkpoint pathways.
2. Diagnosed with NSCLC that harbors an EGFR-sensitizing mutation, ALK
gene translocation, ROS1 gene translocation or RET gene
rearrangement.
a. For nonsquamous and squamous NSCLC, patients with known EGFR
mutation status, ALK translocation, ROS1 translocation, or RET
rearrangement who are sensitive to available targeted inhibitor therapy
are excluded.
b. For nonsquamous NSCLC, patients with unknown EGFR mutation
status will be required to undergo a tissue-based EGFR test locally or at
a central laboratory before randomization. An additional ≥ 6 slides are
required if EGFR mutation status needs to be tested in a central
laboratory. Patients with sensitive EGFR mutation status will be
excluded. Patients with unknown ALK, ROS1, or RET status may be
enrolled.
c. Patients with squamous NSCLC and unknown EGFR, ALK, ROS1, or RET
status will not be required to be tested before randomization.
3. Distant metastasis identified by imaging assessment and/or other
examinations after definitive, platinum-based cCRT.
4. Patients who received chemotherapy and radiotherapy with ≤ 1 cycle
overlap for LA NSCLC.
5. Patients who received systemic anticancer treatment besides the
specified cCRT.
6. Any unresolved toxicity CTCAE > Grade 2 from the prior cCRT. Patients
with irreversible toxicity that is not reasonably expected to be
exacerbated by study treatment may be included (eg, hearing loss).
7. Patients with any grade pneumonitis from prior cCRT.
8. Active autoimmune diseases or history of autoimmune diseases that
may relapse. Note: Patients with the following diseases are not excluded
and may proceed to further screening:
a. Controlled Type I diabetes.
b. Hypothyroidism (provided it is managed with hormone replacement therapy only).
c. Controlled celiac disease.
d. Skin diseases not requiring systemic treatment (eg, vitiligo, psoriasis,
alopecia).
e. Any other disease that is not expected to recur in the absence of
external triggering factors.
9. Any active malignancy ≤ 2 years before the first dose of study
treatment except for the specific cancer under investigation in this study
and any locally recurring cancer that has been treated curatively (eg,
resected basal or squamous cell skin cancer, superficial bladder cancer,
carcinoma in situ of the cervix or breast).
10. Any condition that required systemic treatment with either
corticosteroids (> 10 mg daily of prednisone [in Japan, prednisolone] or
equivalent) or other immunosuppressive medication ≤ 14 days before
the first dose of study treatment.
Note: Patients who are currently or have previously been on any of the
following steroid regimens are not excluded:
a. Adrenal replacement steroid (dose ≤ 10 mg daily of prednisone [in
Japan, prednisolone] or equivalent).
b. Topical, ocular, intra-articular, intranasal, or inhaled corticosteroid
with minimal systemic absorption.
c. Short course (≤ 7 days) of corticosteroid prescribed prophylactically
(eg, for contrast dye allergy) or for the treatment of a non-autoimmune
condition (eg, delayed-type hypersensitivity reaction caused by contact
allergen.
11. Uncontrolled diabetes or > Grade 1 laboratory test abnormalities in
potassium, sodium, or corrected calcium despite standard medical
management or ≥ Grade 3 hypoalbuminemia ≤ 14 days before the first
dose of study treatment.
12. Uncontrollable pleural effusion, pericardial effusion, or ascites
requiring frequent drainage (recurrence within 2 weeks of intervention).
Note for sites in Germany: patients with malignant pleural or pericardial
effusion or ascites are excluded regardless of whether it is
uncontrollable or not.
13. History of interstitial lung disease, non-infectious pneumonitis or
uncontrolled lung diseases including pulmonary fibrosis, acute lung
diseases, etc.
14. Infection (including tuberculosis infection, etc) requiring systemic
antibacterial, antifungal, or antiviral therapy within 14 days before the
first dose of study treatment.
15. Untreated chronic hepatitis B or chronic HBV carriers with HBV DNA
> 500 IU/mL (or > 2500 copies/mL) at screening.
16. Patients with active hepatitis C.
17. Known history of HIV infection. Note for sites in Germany and where
required by Health Authority or local guidance: An HIV serology test
(including antigen and/or antibodies) will be conducted at baseline for
the patients with unknown HIV status and patients with positive HIV
test will be excluded.
18. Any major surgical procedure ≤ 28 days before the first dose of
study treatment. Patients must have recovered adequately from the
toxicity and/or complications from the intervention before the first dose
of study treatment.
19. Prior allogeneic stem cell transplantation or organ transplantation.
[More listed in study protocol] |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
Progression-free survival (PFS) by the Independent Review Committee (IRC), defined as the time from the date of randomization to the date of
first documentation of disease progression assessed by the IRC per
RECIST v1.1 or death, whichever occurs first
|
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
| E.5.2 | Secondary end point(s) |
1 Overall Survival (OS) defined as the time from the date of
randomization until the date of death due to any cause
2 Overall response rate (ORR), defined as the proportion of patients who
achieve a complete response (CR) or partial response (PR) assessed by
both the IRC and investigators per RECIST v1.1
3 Duration of response (DOR), defined as the time from the first
determination of a confirmed objective response assessed by both the
IRC and investigators per RECIST v1.1 until the first documentation of
disease progression or death, whichever occurs first
4 Time to death or distant metastasis (TTDM), defined as the time from
the date of randomization until the first date of distant metastasis
assessed by both the IRC and investigators, or death. Distant metastasis
is defined as any new lesion that is outside of the radiation field per
RECIST v1.1 or proven by biopsy.
5 PFS2, defined as the time from randomization to the disease
progression after next line of treatment, or death from any cause,
whichever occurs first
6 Safety and tolerability, defined as AEs (using NCI CTCAE v5.0),
laboratory tests, vital signs, ECOG Performance Status, physical
examinations, concomitant medications, and dose modifications
7 HRQoL, measured via patient-reported outcomes (PROs) using EORTC
QLQ-C30, EORTC QLQ-LC13, and EQ 5D 5L questionnaires
8 Serum concentrations of ociperlimab and tislelizumab at specified
timepoints
9 Immunogenic responses to ociperlimab and tislelizumab evaluated
through detection of antidrug antibodies
10 PD-L1 and TIGIT expression in archival and/or fresh tumor tissues
before study treatment or at disease progression/reoccurrence, and
their association with clinical efficacy |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | Yes |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | No |
| E.8.1.5 | Parallel group | No |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | Yes |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 3 |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 3 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 59 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
| Australia |
| China |
| Israel |
| Japan |
| Korea, Republic of |
| Taiwan |
| United States |
| France |
| Poland |
| Netherlands |
| Romania |
| Spain |
| Switzerland |
| Germany |
| Italy |
| Belgium |
| Russian Federation |
|
| E.8.7 | Trial has a data monitoring committee | Yes |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
The end of study is defined as the timepoint when the final data point is collected from the last patient in the study. This is when the last patient dies, withdraws consent, completes all study assessments, or is lost to follow-up. Alternatively, the end of study is when the sponsor decides to terminate the study.
|
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 4 |
| E.8.9.1 | In the Member State concerned months | 5 |
| E.8.9.1 | In the Member State concerned days | 12 |
| E.8.9.2 | In all countries concerned by the trial years | 5 |
| E.8.9.2 | In all countries concerned by the trial months | 10 |
| E.8.9.2 | In all countries concerned by the trial days | 30 |
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