1. Study Title:
A Randomized Phase 3 Study of MRTX949 versus Docetaxel in Patients with Previously Treated Non-Small Cell Lung Cancer (NSCLC) with KRAS G12C Mutation
Objectives:
Primary Objective:
- To compare the efficacy of MRTX949 versus docetaxel in overall survival (OS) for NSCLC patients with KRAS G12C mutation.
Secondary Objectives:
- Assess progression-free survival (PFS) using RECIST v1.1 criteria.
- Evaluate objective response rate (ORR) and disease control rate (DCR).
- Measure the duration of response (DoR).
- Determine the safety and tolerability of MRTX949 compared to docetaxel.
- Assess patient-reported outcomes (PROs) like quality of life (QoL).
Endpoints:
Primary Endpoint:
- Overall Survival (OS): Defined as the time from randomization to death due to any cause.
Secondary Endpoints:
- Progression-Free Survival (PFS): Time from randomization to the first documented disease progression or death, whichever occurs first.
- Objective Response Rate (ORR): Proportion of patients achieving a complete response (CR) or partial response (PR) as assessed by independent central review.
- Disease Control Rate (DCR): Proportion of patients achieving CR, PR, or stable disease (SD).
- Duration of Response (DoR): Time from the first documented CR or PR to disease progression or death.
- Safety and Tolerability: Incidence of adverse events (AEs), serious adverse events (SAEs), and treatment-related AEs, graded according to CTCAE v5.0.
- Patient-Reported Outcomes (PROs): Measured using validated QoL instruments (e.g., EQ-5D-5L, EORTC QLQ-C30).
2. Study Title:
An Open-label Phase 1b Study of ORIC-101 in Combination with Anticancer Therapy in Patients with Advanced or Metastatic Solid Tumors
Objectives:
Primary Objectives:
- Evaluate the safety and tolerability of ORIC-101 in combination with anticancer therapy.
- Determine the recommended Phase 2 dose (RP2D) of ORIC-101.
Secondary Objectives:
- Assess preliminary antitumor activity (ORR, PFS, and OS).
- Characterize the pharmacokinetics (PK) of ORIC-101.
Exploratory Objectives:
- Identify biomarkers predicting response to ORIC-101.
- Evaluate patient-reported outcomes (QoL and symptom burden).
Endpoints:
Primary Endpoints:
- Incidence of dose-limiting toxicities (DLTs) during the first cycle of treatment.
- Frequency, severity, and nature of adverse events (AEs) as per CTCAE v5.0.
- Determination of the RP2D based on safety, tolerability, and preliminary efficacy.
Secondary Endpoints:
- Objective response rate (ORR) defined as the proportion of patients achieving complete response (CR) or partial response (PR) based on RECIST v1.1.
- Progression-free survival (PFS), defined as the time from the start of treatment to the first documented disease progression or death.
- Overall survival (OS), defined as the time from the start of treatment to death from any cause.
- Pharmacokinetic parameters of ORIC-101, including maximum plasma concentration (Cmax), time to maximum concentration (Tmax), and area under the curve (AUC).
Exploratory Endpoints:
- Changes in biomarker levels (e.g., gene expression, protein expression, immune markers) associated with ORIC-101 activity.
- Patient-reported outcomes (PROs) using validated instruments (e.g., EQ-5D, EORTC QLQ-C30).
3. Study Title:
Phase 1 Trial of Intralesional Immunotherapy with IFx-Hu2.0 Vaccine in Patients with Advanced Merkel Cell Carcinoma or Cutaneous Squamous Cell Carcinoma
Objectives:
Primary Objective:
- Evaluate the safety and tolerability of IFx-Hu2.0 vaccine in advanced MCC or CSCC patients.
Secondary Objectives:
- Assess immunogenicity through systemic and intralesional immune responses.
- Evaluate preliminary antitumor activity using RECIST 1.1 and immune-related RECIST (iRECIST).
Exploratory Objectives:
- Identify biomarkers predictive of response to IFx-Hu2.0 therapy.
- Study changes in tumor microenvironment post-treatment.
Endpoints:
Primary Endpoints:
- Incidence, severity, and relatedness of adverse events (AEs), graded using CTCAE v5.0.
- Incidence of dose-limiting toxicities (DLTs) within the first 28 days after treatment initiation.
Secondary Endpoints:
- Changes in immune cell populations (e.g., CD8+ T cells, Tregs) in peripheral blood and tumor biopsy samples.
- Levels of cytokines and immune markers (e.g., IFN-γ, IL-2, PD-L1 expression) in serum and tumor microenvironment.
- Objective response rate (ORR) based on RECIST 1.1 and/or iRECIST.
- Duration of response (DoR) and progression-free survival (PFS).
Exploratory Endpoints:
- Correlation of specific biomarkers (e.g., TMB, neoantigen load) with clinical outcomes.
- Changes in gene expression profiles and immune-related pathways in tumor tissue.
4. Study Title:
A Phase-2 Open-label Multicenter Study of Single Agent Enzastaurin in Patients with Relapsed Cutaneous T-cell Lymphoma
Objectives:
Primary Objective:
- Assess the efficacy of single-agent Enzastaurin in relapsed CTCL based on overall response rate (ORR).
Secondary Objectives:
- Evaluate progression-free survival (PFS) and duration of response (DoR).
- Assess overall survival (OS) and safety/tolerability.
- Explore biomarkers linked to Enzastaurin response.
Endpoints:
Primary Endpoint:
- Overall Response Rate (ORR): The proportion of patients who achieve complete response (CR) or partial response (PR) as per predefined criteria (e.g., International Society for Cutaneous Lymphomas guidelines).
Secondary Endpoints:
- Progression-Free Survival (PFS): Time from the start of treatment to disease progression or death from any cause, whichever occurs first.
- Duration of Response (DoR): Time from the first documented response (CR or PR) to disease progression or death.
- Overall Survival (OS): Time from the start of treatment to death from any cause.
- Safety endpoints: Incidence, severity, and type of treatment-emergent adverse events (TEAEs) graded according to CTCAE v5.0.
- Exploratory biomarker endpoints: Association of specific biomarkers with ORR, PFS, and DoR.
5. Study Title:
Evaluating the Efficacy and Safety of Pembrolizumab Versus Placebo in Patients with Advanced Non-Small Cell Lung Cancer (NSCLC): A Phase III Randomized Controlled Trial
Objectives:
Primary Objective:
- Compare pembrolizumab versus placebo in prolonging PFS in advanced NSCLC patients.
Secondary Objectives:
- Assess overall survival (OS) between treatment groups.
- Evaluate ORR based on RECIST v1.1.
- Measure DoR in confirmed responders.
- Analyze the safety profile of pembrolizumab.
Exploratory Objectives:
- Explore the correlation between PD-L1 levels and treatment efficacy.
- Assess QoL using patient-reported outcome measures.
Endpoints:
Primary Endpoint:
- Progression-Free Survival (PFS): Defined as the time from randomization to the first documented disease progression or death due to any cause, whichever occurs first, based on RECIST v1.1 criteria as assessed by blinded independent central review (BICR).
Secondary Endpoints:
- Overall Survival (OS): Defined as the time from randomization to death due to any cause.
- Objective Response Rate (ORR): Proportion of patients achieving a complete response (CR) or partial response (PR) per RECIST v1.1.
- Duration of Response (DoR): Time from first documented CR or PR to disease progression or death.
- Safety: Incidence of treatment-emergent adverse events (TEAEs) graded according to CTCAE v5.0.
Exploratory Endpoints:
- PD-L1 expression correlation with efficacy.
- Changes in quality of life (QoL) scores from baseline.