Efficacy of Cobolimab, Dostarlimab, and Docetaxel in Advanced Non-Small Cell Lung Cancer Post Anti-PD(L)1 Therapy and Chemotherapy
- Trial ID
- 2023-507475-21-00
- Protocol
- 213410
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this study is to evaluate the **efficacy** of the combination therapy of cobolimab, dostarlimab, and docetaxel compared to docetaxel alone in participants with advanced non-small cell lung cancer (NSCLC) who have progressed following prior anti-PD-1 or anti-PD-L1 therapy and chemotherapy. Additionally, the study aims to assess the efficacy of dostarlimab combined with docetaxel relative to docetaxel alone in the same patient population. This evaluation is clinically relevant as it seeks to determine the potential benefits of combination therapies in improving outcomes for patients with advanced NSCLC, a condition with limited treatment options after progression on standard therapies.
Secondary objectives include: - Evaluating the efficacy of cobolimab, dostarlimab, and docetaxel relative to dostarlimab and docetaxel. - Assessing additional measures of clinical benefit for cobolimab, dostarlimab, and docetaxel compared to docetaxel alone. - Evaluating additional measures of clinical benefit for dostarlimab and docetaxel relative to docetaxel alone. - Assessing additional measures of clinical benefit for cobolimab, dostarlimab, and docetaxel compared to dostarlimab and docetaxel. - Evaluating the safety and tolerability of cobolimab, dostarlimab, and docetaxel, as well as dostarlimab and docetaxel, compared to docetaxel alone.
Participants
The clinical trial involves a total of **320 participants** diagnosed with **Non-Small Cell Lung Cancer (NSCLC)**. The study population includes both male and female subjects, aged **18 years and older**, with a focus on those who have advanced or metastatic NSCLC. Participants were selected based on their progression on prior anti-PD-1 or anti-PD-L1 therapy and chemotherapy. The trial includes individuals who have received no more than two prior lines of therapy for advanced or metastatic disease, specifically a platinum-based chemotherapy regimen and an anti-PD-1 or anti-PD-L1 antibody. Participants must have measurable disease as per RECIST v1.1 criteria and documented radiological disease progression on prior treatments. The trial population is inclusive of vulnerable groups, ensuring a comprehensive evaluation of the treatment efficacy across diverse demographics. Lifestyle factors such as diet and physical activity are not specified in the available data. Key inclusion criteria require participants to provide written informed consent and submit an archival FFPE tumor tissue specimen, with a fresh biopsy encouraged for biomarker analysis.
Plans and Procedures
The clinical trial is designed as a **randomized**, open-label, Phase 2/3 study to evaluate the efficacy of **cobolimab**, **dostarlimab**, and **docetaxel** in participants with advanced **non-small cell lung cancer** (NSCLC) who have progressed on prior anti-PD-1 or anti-PD-L1 therapy and chemotherapy. The trial involves three arms: cobolimab + dostarlimab + docetaxel, dostarlimab + docetaxel, and docetaxel alone. The primary objective is to assess the overall survival (OS) of the triplet and doublet combinations compared to docetaxel alone. Secondary endpoints include progression-free survival (PFS), overall response rate (ORR), duration of response (DOR), and safety assessments.
The trial is expected to last until November 2025, with participant recruitment having commenced in February 2021. Participants will be involved in the study for a maximum treatment period of 1188 days. The study includes several key visits: an initial screening visit to confirm eligibility, regular follow-up visits to monitor treatment response and safety, and an end-of-study visit to assess final outcomes. Participants must be at least 18 years old, have histologically or cytologically confirmed advanced or metastatic NSCLC, and have measurable disease according to RECIST v1.1 criteria. They should have progressed on prior platinum-based chemotherapy and anti-PD-1 or anti-PD-L1 therapy.
Participants may be withdrawn from the study early due to reasons such as disease progression, unacceptable toxicity, or withdrawal of consent. The study will utilize intravenous administration of the investigational products, with dosing regimens tailored to each treatment arm. The trial will adhere to rigorous safety monitoring protocols to ensure participant well-being throughout the study duration.
Treatment
The clinical trial involves the administration of several experimental medications, each with specific characteristics and administration protocols. **Docetaxel Hikma** is utilized in three different concentrations: 20 mg/1 ml, 80 mg/4 ml, and 160 mg/8 ml. All formulations are presented as a **solution for infusion** and are administered via **intravenous use**. The active substance, **docetaxel**, is of chemical origin. The maximum daily and total dose for each formulation is 75 mg/m², with a maximum treatment period of 1188 days. These formulations are produced by Hikma Farmacêutica (Portugal), S.A.
**JEMPERLI**, containing the active substance **dostarlimab**, is provided as a 500 mg concentrate for solution for infusion. This medication is administered through **intravenous infusion**. Dostarlimab is a protein-based substance, and the maximum daily and total dose is 500 mg. The treatment period is also capped at 1188 days. The product is manufactured by GlaxoSmithKline (Ireland) Limited. The use of a closed system transfer device is permitted for the transfer of dostarlimab 50 mg/mL solution in a clinical setting, ensuring compatibility as detailed in the study's documentation.
**Cobolimab** is another investigational product in this trial, provided as a solution for infusion. The active substance, cobolimab, is a protein-based compound. The maximum daily and total dose is 300 mg, with a treatment period of up to 1188 days. This product is also manufactured by GlaxoSmithKline. The administration route is **intravenous use**.
In this study, the experimental treatments are compared against each other and against a standard treatment regimen involving docetaxel alone. The trial aims to evaluate the efficacy of the combination therapies in participants with advanced non-small cell lung cancer (NSCLC) who have progressed on prior anti-PD-1 or anti-PD-L1 therapy and chemotherapy. Participant compliance with the dosing schedule is monitored throughout the trial to ensure adherence to the treatment protocol.
Efficacy
The efficacy of the clinical trial will be assessed by comparing the treatment regimens of **cobolimab**, **dostarlimab**, and **docetaxel** against **docetaxel** alone in participants with advanced non-small cell lung cancer (NSCLC) who have progressed on prior anti-PD-1 or anti-PD-L1 therapy and chemotherapy. The primary endpoints for efficacy evaluation include overall survival (OS), defined as the duration from the date of randomization to the date of death by any cause. This will be measured for both the triplet therapy (cobolimab + dostarlimab + docetaxel) and the doublet therapy (dostarlimab + docetaxel) compared to docetaxel alone.
Secondary endpoints will further assess the efficacy of the triplet therapy relative to the doublet therapy, with OS as a key measure. Additional secondary endpoints include confirmed objective response rate (ORR), progression-free survival (PFS), duration of response (DOR), time to deterioration (TTD), and changes from baseline as assessed by the EORTC-QLQ-C30 and EORTC-QLQ-LC13 domains. The study will also evaluate the safety and tolerability of the treatment arms by monitoring the incidence of treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), immune-related adverse events (irAEs), TEAEs leading to death, and adverse events leading to discontinuation. These safety parameters will be observed while participants are on treatment and up to 90 days after the last dose of study treatment.
Inclusion and Exclusion Criteria
Inclusion Criteria
- "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. Note: Participants in Korea are eligible if they are 19 years or older at the time consent is obtained."
- "Participant has histologically or cytologically proven advanced or metastatic NSCLC, and only squamous or nonsquamous cell carcinoma."
- "Participant has received no more than 2 prior lines of therapy for advanced or metastatic disease, which must only include a platinum-based (e.g., cisplatin, carboplatin) doublet chemotherapy regimen and an anti-PD-1 or anti-PD-L1 antibody (no other biologic alone or in combination; novel combinations are not allowed). Participants previously treated with targeted therapies, including angiogenesis inhibitors (e.g., bevacizumab, ramucirumab, lenvatinib), are not eligible. 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-1 or anti-PD-L1 antibody Note the following: − An anti-PD-1 or anti-PD-L1 antibody received during a previous clinical study meets this requirement if the antibody has been approved for an indication in at least 1 country. − 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-1 or anti-PD-L1 antibody) as part of standard of care and have relapsed within 1 year of the first dose of chemoradiotherapy fulfill the protocol requirement for platinum-based chemotherapy and anti-PD-1 or anti-PD-L1 antibody therapy. These regimens are considered 1 line of therapy for stratification purposes. − The anti-PD-1 or anti-PD-L1 antibody can be administered with the platinum-based chemotherapy, and this is considered 1 line of therapy with both agents and no other lines are allowed. − The anti-PD-1 or anti-PD-L1 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-1 or anti-PD-L1 antibody, discontinued from that therapy, experienced disease progression, and are then retreated with an anti-PD-1 or anti-PD-L1 antibody will be considered as having had 1 line of anti-PD-1 or anti-PD-L1 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."
- "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."
- "Participant has documented radiological disease progression on prior platinum-based chemotherapy and on prior anti-PD-1 or anti-PD-L1 therapy according to RECIST v1.1."
- "Participant agrees to submit an archival FFPE tumor tissue specimen that was collected on or after diagnosis of metastatic disease from location(s) not irradiated prior to biopsy. Both tissue block and freshly cut slides are acceptable. If archival tissue is not available, the participant must undergo biopsy prior to study entry. See the Study Reference Manual for further details. a. Participants are also encouraged, but not required, to have a fresh tumor tissue biopsy of a primary or metastatic tumor prior to dosing (samples will be used to enable biomarker analysis). For a full list of Inclusion criteria please refer to the Study Protocol Section 5.1 Inclusion Criteria pg57-61 "
Exclusion Criteria
- "Participant has been previously treated with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent that resulted in permanent discontinuation due to an AE."
- "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."
- Participant has been previously treated with an anti-TIM-3 or anti-CTLA-4 agent or docetaxel.
- "Participant has a documented sensitizing EGFR, ALK, or ROS-1 mutation. Participants whose tumors have not been tested for these driver mutations and therefore who have unknown driver mutation status are not eligible. Participants with squamous histology do not need to be tested for these driver mutations."
- "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."
- "Participant has received radiation to the lung that is >30 Gy within 6 months prior to the first dose of study treatment."
- "Participant has completed palliative radiotherapy within 7 days prior to the first dose of study treatment."
- "Participant is ineligible if any of the following hepatic characteristics are present: a) Alanine aminotransferase (ALT) >2.5×ULN b) ALT and/or aspartate aminotransferase (AST) >1.5×upper limit of normal (ULN) concomitant with alkaline phosphatase (ALP) >2.5×ULN c) Bilirubin >1×ULN d) 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."
- "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)."
- "Participant has had major surgery within 3 weeks prior to the first dose of study treatment or 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."
- "Participant has known new or progressive brain metastases and/or leptomeningeal metastases. Participants who have received prior therapy for their brain metastases and have radiologically stable central nervous system disease may participate, provided they are neurologically stable for at least 4 weeks before study entry and are off corticosteroids within 3 days prior to the first dose of study treatment."
- "Participant has tested positive for the following at Screening or within 3 months before the first dose of study treatment: a. Presence of hepatitis B surface antigen. b. Presence of hepatitis C antibody in the absence of an RNA test for hepatitis C virus. If a confirmatory RNA test is available, a positive test result will exclude a participant, while a negative test result (indicating absence of active infection) will allow the participant to enter into the study."
- "Participant has an active infection requiring systemic therapy within 1 week prior to the anticipated first dose of study treatment."
- "Participant has known HIV (positive for HIV-1 or HIV-2 antibodies). For a full list of Exclusion criteria please refer to the Study Protocol Section 5.2 Exclusion Criteria pg61-64"
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Belgium | Not Recruiting | 01 Feb 2021 | 11 |
 Finland | Not Recruiting | 01 Feb 2021 | 8 |
 France | Not Recruiting | 01 Feb 2021 | 56 |
 Germany | Not Recruiting | 01 Feb 2021 | 66 |
 Greece | Not Recruiting | 01 Feb 2021 | 33 |
 Italy | Not Recruiting | 01 Feb 2021 | 70 |
 The Netherlands | Not Recruiting | 01 Feb 2021 | — |
 Poland | Not Recruiting | 01 Feb 2021 | 30 |
 Romania | Not Recruiting | 01 Feb 2021 | 49 |
 Spain | Not Recruiting | 01 Feb 2021 | 80 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
Docetaxel Hikma 20 mg/1 ml Konzentrat zur Herstellung einer Infusionslösung | Comparator | KONZENTRAT ZUR HERSTELLUNG EINER INFUSIONSLÖSUNG | INTRAVENOUS USE | 75 | 1188 | PRD4495641 |
Docetaxel Hikma 80 mg/4 ml Konzentrat zur Herstellung einer Infusionslösung | Comparator | KONZENTRAT ZUR HERSTELLUNG EINER INFUSIONSLÖSUNG | INTRAVENOUS USE | 75 | 1188 | PRD4495642 |
Docetaxel Hikma 160 mg/8 ml Konzentrat zur Herstellung einer Infusionslösung | Comparator | KONZENTRAT ZUR HERSTELLUNG EINER INFUSIONSLÖSUNG | INTRAVENOUS USE | 75 | 1188 | PRD4495643 |
JEMPERLI 500 mg concentrate for solution for infusion | Test | CONCENTRATE FOR SOLUTION FOR INFUSION | INTRAVENOUS INFUSION | 500 | 1188 | PRD8877508 |