Efficacy Comparison of Cobolimab + Dostarlimab + Docetaxel to Dostarlimab + Docetaxel to Docetaxel Alone in Participants with Advanced Nonsmall Cell Lung Cancer Who Have Progressed on Prior Anti PD (L)1 Therapy and Chemotherapy
- Conditions
- onsmall 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
- EUCTR2020-003433-37-IT
- Lead Sponsor
- GLAXOSMITHKLINE RESEARCH AND DEVELOPMENT
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 750
Participants are eligible to be included in the study only if all of the following criteria apply:
1. Participant is =18 years old, is able to understand the study procedures, and agrees to participate in the study by providing written informed consent (as described in Appendix 5), which includes compliance with the requirements and restrictions listed in the ICF and in this protocol.
2. Participant has histologically or cytologically proven advanced or metastatic NSCLC, including squamous or nonsquamous cell carcinoma.
3. Participant has received no more than 2 prior lines of therapy, which must include a platinum-based chemotherapy (eg, cisplatin, carboplatin) and an anti-PD-(L)1 antibody.
a. Two components of treatment must have been received in the same line or as separate lines of therapy as follows:
-A maximum of 1 line of therapy containing a platinum-based chemotherapy in the metastatic setting
and
-A maximum of 1 line of therapy containing an anti-PD-(L)1 antibody
Note the following:
- Anti-PD-(L)1 antibody received during a previous clinical study may meet this requirement upon consultation with the GSK Medical Monitor.
- Participants from the Phase 3 PACIFIC clinical study (NCT02125461) who received the experimental regimen (chemoradiotherapy followed by durvalumab) (Antonia, 2017) or participants who received a regimen similar to the PACIFIC regimen (chemoradiotherapy followed by an anti- PD-(L)1 antibody) as part of standard of care and have relapsed within 1 year of the first dose of chemoradiotherapy fulfill the protocol requirement for platinumbased chemotherapy and anti-PD-(L)1 antibody therapy. These regimens are considered 1 line of therapy for stratification purposes.
- The anti-PD-(L)1 antibody can be administered with the platinumbased chemotherapy, and this is considered 1 line of therapy with both agents and no other lines are allowed.
- The anti-PD-(L)1 antibody may be counted as a prior treatment if the antibody is approved in at least 1 country for the treatment of cancer.
Participants who have completed 2 years of treatment with pembrolizumab or another anti-PD-(L)1 antibody, discontinued from that therapy, experienced disease progression, and are then retreated with an anti-PD-(L)1 antibody will be considered as having had 1 line of anti- PD-(L)1 therapy.
- Adjuvant or neoadjuvant 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.
4. Participant has measurable disease, that is, presenting with at least 1 measurable lesion per RECIST v1.1 as determined by the local site Investigator/radiology assessment.
Target lesions situated in a previously irradiated area are considered measurable if disease progression has been demonstrated in such lesions and if there are other target lesions. If there is only 1 target lesion that was previously irradiated, the participant is not eligible. See Appendix 1 for the definition of a measurable lesion.
5. Participant has documented radiographic disease progression on prior platinum-based chemotherapy and on prior anti-PD-(L)1 therapy according to RECIST v1.1.
For a full list of Inclusion criteria please refer to the Study Protocol.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 308
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range
Participants are excluded from the study if any of the following criteria apply:
1. Participant has been previously treated with an anti-PD-(L)1 or anti- PD-L2 agent thatresulted in permanent discontinuation due to an AE.
2. Participant has been previously treated with an anti-TIM-3 or anti- CTLA-4 agent or docetaxel.
3. Participant has known a ctionable driver mutations such as EGFR mutation, ALK translocation, NTRK fusions, ROS1 rearrangement, or BRAF V600E mutation.
Note: Participants whose tumors have not been tested for driver mutations and therefore who have unknown driver mutation status are eligible.
4. Participant had radiological or clinical disease progression (ie, worsening performance status, clinical symptoms, and laboratory data) =8 weeks after initiation of prior anti-PD-1 or anti-PD-L1 antibody. The clinical disease progression should have been confirmed by a subsequent radiological scan.
5. Participant has received radiation to the lung that is >30 Gy within 6 months prior to the first dose of study treatment.
6. Participant has completed palliative radiotherapy within 7 days prior to the first dose of study treatment.
7. Participant is ineligible if any of the following hepatic characteristics are present:
a. Alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) >1.5×upper limit of normal (ULN) concomitant with alkaline phosphatase (ALP) >2.5×ULN
b. Bilirubin >1×ULN
c. Current active liver or biliary disease (with the exception of Gilbert's syndrome or asymptomatic gallstones, liver metastases, or otherwise stable chronic liver disease per the Investigator's assessment)
Note: Stable chronic liver disease should generally be defined by the absence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, persistent jaundice, or cirrhosis.
8. Participant has a corrected QT interval (QTc) >450 msec (or QTc >480 msec for participants with bundle branch block).
Note the following:
-The QTc is the QT interval corrected for heart rate according to Bazett's formula (QTcB), Fridericia's formula (QTcF), and/or another method, machine-read or manually over-read.
-The specific formula that will be used to determine eligibility and discontinuation for an individual participant should be determined prior to initiation of the study. In other words, several different formulae cannot be used to calculate the QTc for an individual participant, and then, the lowest QTc value used to include or discontinue the participant from the study.
-For purposes of data analysis, QTcB, QTcF, another QT correction formula, or a composite of available values of QTc will be used as specified in the Statistical Analysis Plan (SAP).
9. Participant has had major surgery within 3 weeks prior to the first dose of study treatmentor has not adequately recovered from any AEs (Grade =1) and/or complications from any major surgery. Surgical implantation of a port catheter is not exclusionary.
10. Participant has an additional malignancy or a history of prior malignancy, with the exception of adequately treated basal or squamous skin cancer, cervical carcinoma in situ, or bladder carcinoma in situ without evidence of disease, or had a malignancy treated with curative intent and with no evidence of disease recurrence for 5 years since the initiation of that therapy.
For a full list of Exclusion criteria please refer to the Study Protocol.
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