| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| non-small cell lung cancer (NSCLC) |
|
| 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 |
Determine whether experimental regimens
provide evidence for improved survival over
SoC therapy |
|
| E.2.2 | Secondary objectives of the trial |
-Evaluate milestone survival in participants
treated with experimental regimens versus
SoC therapy for NSCLC
-Evaluate other measures of antitumor
activity of the experimental regimens
compared with SoC therapy for NSCLC
(RECIST 1.1 and iRECIST)
-Evaluate the safety and tolerability of the
experimental regimens compared with SoC
therapy for NSCLC
-Characterize the pharmacokinetic properties
of GSK3359609 (ICOS Agonist) when given
in combination with chemotherapy and/or
other immunotherapies |
|
| E.2.3 | Trial contains a sub-study | Yes |
| E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Substudy 1 is docetaxel versus docetaxel + GSK3359609; date and version are as per the main protocol; objectives are per main protocol.
See Sec 12.1.2 of 205801 protocol. |
|
| E.3 | Principal inclusion criteria |
Participants are eligible to be included in the study only if all the following criteria apply:
1. Capable of giving signed informed consent/assent as described in Section 12.4 of protocol which includes compliance with the requirements and restrictions listed in the ICF and in this protocol
2. Male or female, aged 18 years or older at the time consent is obtained
3. Histologically or cytologically confirmed diagnosis of NSCLC (squamous or nonsquamous)
and:
a. Documented disease progression (for example, based on radiographic imaging) during or after a maximum of 2 lines of systemic treatment for locally/regionally advanced recurrent, Stage IIIb/Stage IV or metastatic disease:
i. A maximum of 1 line of platinum-containing chemotherapy regimen in the metastatic setting, and ii. A maximum of 1 line of PD(L)1 mAb containing regimen.
Notes:
o PD(L)1 mAb received during a previous clinical trial may meet this requirement upon consultation with study medical monitor.
o Participants on the phase III PACIFIC trial (NCT02125461) experimental regimen (chemoradiotherapy followed by durvalumab) [Antonia, 2017] or received the PACIFIC regimen [chemoradiotherapy followed by PD(L)1] as part of SoC AND have relapsed within one year from the first dose of chemoradiotherapy would fulfill the protocol requirement for platinum-based chemotherapy treatment and PD-1 treatment.
This would be considered a single line of treatment for the purpose of PD(L)1 line of therapy stratification.
o PD(L)1 mAb can be administered with the platinum-based chemotherapy regimen and this would count as a single line of therapy.
o PD(L)1 mAb may be counted as a prior treatment if the agent is approved in at least 1 country for the treatment of cancer.
o Participants who have completed 2 years of pembrolizumab or another PD(L)1 mAb, discontinue from that therapy, experience disease progression, and are then retreated with PD(L)1, will be considered as
having had one line of PD(L)1 therapy.
o Adjuvant or neo-adjuvant systemic anticancer therapy will not count toward the 2 lines of therapy unless disease recurs during the first year following the start of adjuvant chemotherapy.
b. Participants with known BRAF molecular alterations must have had disease progression after receiving the locally available SoC treatment for the molecular alteration.
4. Measurable disease, presenting with at least 1 measurable lesion per RECIST 1.1 (see Appendix 12 of protocol for definition of a measurable lesion)
5. Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) score of 0 or 1
6. A tumor tissue sample obtained at any time from the initial diagnosis of NSCLC to time of study entry is mandatory. Although a fresh tumor tissue sample obtained during screening is preferred, archival tumor specimen is acceptable. See Section 9.7.2 of protocol for further details on tumor tissue requirements.
7. Adequate organ function as defined in Table 6 in protocol
8. A male participant must agree to use a highly effective contraception as detailed in Appendix 6 of this protocol during the treatment period and for at least 120 days after the last dose of study treatment and refrain from donating sperm during this period.
Note: If the participant is randomized to the SoC regimen only, then the duration of contraception is at least 3 days after the last dose of study treatment.
9. A female participant is eligible to participate if she is not pregnant (see Appendix 6 of protocol), not breastfeeding, and at least 1 of the following conditions apply:
i. Not a woman of childbearing potential (WOCBP) as defined in Appendix 6 of protocol
OR
ii. A WOCBP who agrees to follow the contraceptive guidance in Appendix 6 of protocol during the treatment period and for at least 120 days after the last dose of study treatment.
Note: If the participant is randomized to the SoC regimen only, then the duration of contraception is at least 3 days after the last dose of study treatment (or per institutional standard) |
|
| E.4 | Principal exclusion criteria |
Participants are excluded from the study if any of the following criteria apply:
1. Received prior treatment with the following therapies (calculation is based on date of last therapy to date of first dose of study treatment):
a. Docetaxel at any time
b. Any of the investigational agents being tested in the current study, including experimental ICOS agonist
c. Systemic approved or investigational anticancer therapy within 30 days or 5 half-lives of the drug, whichever is shorter. At least 14 days must have elapsed between the last dose of prior anticancer agent and the first dose of study drug is administered.
d. Prior radiation therapy: permissible if at least one non-irradiated measurable lesion is available for assessment per RECIST version 1.1
or if a solitary measurable lesion was irradiated, objective progression is documented. A wash out of at least 2 weeks before start of study drug for radiation of any intended use is required.
2. Received ≥3 prior lines of therapy for NSCLC, including participants with BRAF molecular alternations. (See inclusion criterion #3 for eligible lines of therapy guidance of protocol)
Note: Patients with known EGFR/ALK/ROS1 molecular alterations are excluded from participation in this study.
3. Invasive malignancy or history of invasive malignancy other than disease under study within the last 2 years, except as noted below:
- Any other invasive malignancy for which the participant was definitively treated, has been disease-free for ≤2 years and in the opinion of the principal investigator and GSK Medical Monitor will not affect the evaluation of the effects of the study treatment on the currently targeted malignancy, may be included in this clinical trial.
- Curatively treated non-melanoma skin cancer or successfully treated in situ carcinoma.
4. Central nervous system (CNS) metastases, with the following exception:
Participants with asymptomatic CNS metastases who are clinically stable and have no requirement for steroids for at least 14 days prior to first dose of study treatment.
Note: Participants with carcinomatous meningitis or leptomeningeal spread are excluded regardless of clinical stability.
5. Major surgery ≤28 days of first dose of study treatment.
6. Autoimmune disease (current or history) or syndrome that required systemic treatment within the past 2 years. Replacement therapies which include physiological doses of corticosteroids for treatment of endocrinopathies (for
example, adrenal insufficiency) are not considered systemic treatments.
7. Receiving systemic steroids (≥10 mg oral prednisone or equivalent) or other immunosuppressive agents within 7 days prior to first dose of study treatment.
Note: Steroids as premedication for hypersensitivity reactions (e.g., computed tomography [CT] scan premedication) are permitted.
8. Prior allogeneic/autologous bone marrow or solid organ transplantation.
9. Receipt of any live vaccine within 30 days prior to first dose of study treatment.
Examples of live vaccines include, but are not limited to the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus
Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (for example, FluMist) are live attenuated vaccines and are not allowed.
10. Toxicity from previous anticancer treatment that includes:
a. ≥ Grade 3 toxicity considered related to prior immunotherapy and that led to treatment discontinuation.
b. Toxicity related to prior treatment that has not resolved to ≤Grade 1 (except alopecia, hearing loss, endocrinopathy managed with replacement therapy, and peripheral neuropathy which must be ≤Grade 2).
11. History (current and past) of idiopathic pulmonary fibrosis, pneumonitis (for past pneumonitis exclusion only if steroids were required for treatment), interstitial lung disease, or organizing pneumonia.
Note: post-radiation changes in the lung related to prior radiotherapy and/or asymptomatic radiation-induced pneumonitis not requiring treatment may be permitted if agreed upon by the investigator and Medical Monitor.
12. Recent history (within the past 6 months) of uncontrolled symptomatic ascites, pleural or pericardial effusions
13. Recent history (within the past 6 months) of gastrointestinal obstruction that required surgery, acute diverticulitis, inflammatory bowel disease, or intraabdominal abscess
Refer protocol for other exclusion criteria |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| Overall survival as measured by time from randomization to death |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| Following discontinuation of study treatment, participants will be followed every 12 weeks for disease progression until death or withdrawal from further contact |
|
| E.5.2 | Secondary end point(s) |
-Milestone survival rate at 12 and 18 months
-CR, PR, SD, PD, PFS, ORR, DOR
iCR, iPR, iUPD, iCPD, iSD
iPFS; iORR; iDOR
-Frequency and severity of AEs, AESI; SAEs and AE/SAEs leading to dose modifications/delays/withdrawals; changes in laboratory, vital signs, and safety assessment parameters, including immunogenicity (ADA)
-Plasma PK parameters that include Cmax and Cmin for GSK3359609 and SoC in combination (and investigational agent/s included in other arms) and for SoC alone, as data permit. |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. Survival rate at 12 mos & 18 mos
2. Time of response.
3. AEs, SAEs, AESI from time of consent until 90 days after last dose. Safety monitoring throughout by evaluation of dose modification/delays/withdrawals, lab values, vital signs, immunogenicity, etc.
4. PK SoC: predose Day 1, end of infusion (EOI), & between 2 and 5 hours after EOI for all indicated visits. PK GSK3359609: predose for all marked visits, Week 1 (Day 1) at EOI & EOI+4h, Week 13 and 25, & then every 12 weeks at predose. |
|
| 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) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| 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 | 2 |
| 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 | 6 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 50 |
| 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 |
| Canada |
| Korea, Republic of |
| United States |
| 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
|
|
| 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 | 2 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 4 |
| E.8.9.2 | In all countries concerned by the trial months | 2 |
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