Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Lung Neoplasms

Carcinoma, Non-Small-Cell Lung

Carcinoma

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

Pharmaceutical Solutions

All Drugs and Chemicals

Antineoplastic Agents

Durvalumab

Olaparib

Antineoplastic Agents, Immunological

Poly(ADP-ribose) Polymerase Inhibitors

Enzyme Inhibitors

Investigator's choice single-agent chemotherapy plus durvalumab 1500 mg every 3 weeks.

Investigator's choice single-agent chemotherapy.

Investigator's choice platinum doublet chemotherapy plus durvalumab 1500 mg every 3 weeks for 4 cycles followed by maintenance durvalumab 1500 mg every 3 weeks plus olaparib 300 mg twice daily.

Investigator's choice platinum doublet chemotherapy plus durvalumab 1500 mg every 3 weeks for 4 cycles followed by maintenance durvalumab 1500 mg every 3 weeks

Durvalumab concentrate for solution for infusion will be supplied in glass vials containing 500 mg durvalumab at a concentration of 50 mg/mL

Olaparib tablets (100 mg and 150 mg strengths) supplied in high-density polyethylene (HDPE) bottles.

Olaparib tablet

Investigator's choice single-agent chemotherapy regimen

Single-agent chemotherapy

Investigator's choice platinum doublet chemotherapy

Platinum doublet chemotherapy

Federico Cappuzzo, MD

Lorenza Landi, MD

This is a randomized, non-comparative, phase II study investigating whether: 1) the addition of durvalumab to investigator's choice second line chemotherapy prolongs survival versus investigator's choice second line chemotherapy in NSCLC patients with locally advanced disease progressing on durvalumab given after concomitant chemoradiotherapy; 2) whether the addition of olaparib to durvalumab improves survival over durvalumab alone after induction chemoimmunotherapy in patients relapsing after completing durvalumab maintenance therapy for stage III disease.

After evaluation of inclusion and exclusion criteria and after consent form signature, all eligible patients progressing during durvalumab therapy will be in the Part A of the trial randomized to in a 1:1 ratio to investigator's choice single-agent chemotherapy plus durvalumab (Arm A: experimental arm) or to investigator's choice single-agent chemotherapy (Arm B: standard arm). In the clinical trial's Part B, patients progressing after completion of durvalumab therapy will be further randomized in a 1:1.7 ratio to investigator's choice platinum doublet chemotherapy plus durvalumab for 4 cycles followed by maintenance durvalumab plus olaparib (Arm C: experimental arm) or to investigator's choice platinum doublet chemotherapy plus durvalumab for 4 cycles followed by durvalumab (Arm D: experimental arm). Therapy will be continued up to disease progression, toxicity or patient refusal.

In the group of individuals progressing during durvalumab theray, patients will be randomized to the experimental arm (durvalumab+chemotherapy) or to the standard arm (chemotherapy alone). The standard arm will act as a calibration arm.

In the second groups patients will be randomized to the experimental arm durvalumab+chemotherapy followed by maintenance durvalumab+olaparib or to the other experimental arm durvalumab+chemotherapy followed by maintenance durvalumab.

Randomized Trial Comparing Standard of Care Versus Immune- Based Combination in Relapsed Stage III Non-small-cell Lung Cancer (NSCLC) Pretreated With Chemoradiotherapy and Durvalumab

Phase II, Two-cohorts, Randomized Trial Comparing Standard of Care Versus Immune- Based Combination in Relapsed Stage III Non-small-cell Lung Cancer (NSCLC) Pretreated With Chemoradiotherapy and Durvalumab (MEDI4736)

Overall Survival (OS) rate at 12 months in patients treated in arm A versus B and in patients treated in arm C versus arm D.

Progression free survival (PFS) will be calculated from the date of randomization to the first documented evidence of progressive disease or death due to any cause (whichever occurs first) in patients treated in arm A versus B and in patients treated in arm C versus arm D.

Objective response rate (ORR) is defined as the number of subjects with a best overall response (BOR) of CR or PR divided by the number of randomized subjects for each treatment in each coort.

All adverse events will be reported until 30 days after the final dose of study treatment or until initiation of new systemic anti-cancer therapy, whichever occurs first, and serious adverse events and adverse events of special interest will continue to be reported until 90 days after the final dose of study treatment or until initiation of new systemic anti-cancer therapy, whichever occurs first.

Progression-free survival (PFS) and Overall survival (OS) will be evaluated according to biomarkers ((i.e., PD-L1, ERCC1, SLFN11, STK11, KEAP1, p53 expression, DNA repair genes \[including BRCA 1-2 mutations\] and tumor mutational burden).

Fondazione Ricerca Traslazionale

Paclitaxel

Albumin-Bound Paclitaxel

Carboplatin

Pemetrexed

Dose escalation part Golidocitinib in combination with sintilimab

Dose expansion cohort 1, Golidositinib plus Sintilimab following Sintilimab

Dose expansion cohort 2, Golidositinib plus Sintilimab following Sintilimab + chemotherapy

Golidocitinib

Sintilimab, 200mg, intravenous, every 3 weeks.

Sintilimab

Pemetrexed or nab-paclitaxel +carboplatin, intravenous, every 3 weeks for 2 cycles

platinum doublet chemotherapy

Jie Wang, MD,PhD

Jie Wang, MD, PhD

This is a phase 2 Study to investigate the safety, tolerability, and anti-tumor activity of golidocitinib in combination with sintilimab as the front-line treatment for patients with metastatic PD-L1 positive non-small cell lung cancer (NSCLC)

Golidocitinib in Combination With Sintilimab for PD-L1 Selected Treatment Locally Advanced or Metastatic Non-Small Cell Lung Cancer(NSCLC)

A Phase 2, Open-label, Single Arm Study to Investigate the Safety and Efficiency of Golidocitinib in Combination With Sintilimab in Patients With Locally Advanced or Metastatic Non-Small Cell Lung Cancer (NSCLC) With PD-L1TPS ≥ 1%)

Complete response (CR) or partial response (PR) per investigator assessment according to RECIST 1.1

Time from first administration of study drug to first documented disease progression or death per investigator assessment according to RECIST 1.1

time from first administration of study drug to death

Frequency an severity of AEs according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.

Dizal Pharmaceuticals

Cancer Institute and Hospital, Chinese Academy of Medical Sciences

Chief Physician

1. Non-squamous histology:

   * Compound 121564 10 mg/Kg administered over 60 minutes given intravenously every 2 weeks for 4 doses.
   * Compound 565994 500 mg/m2 administered over 10 minutes, and
   * Compound 232673 AUC=5 mg/mL/min administered over 15-60 minutes or Compound 454893 at 75 mg/m2 over 1 hour.
   * Compound 565994 and platinum are to be given on day 1 of every 3-week cycle for 3 cycles.
2. Squamous histology:

   * Compound 121564 10 mg/Kg administered over 60 minutes every 2 weeks for 4 doses.
   * Compound 232673 AUC=5 mg/mL/min administered over 15-60 minutes or Compound 454893 at 75 mg/m2 over 1 hour on day 1 of every cycle.
   * Compound 343782 1,000 mg/m2 administered over 30 minutes on days 1 and 8 of each cycle.
   * Platinum and Compound 343782 will be given for 3 cycles.

Compound 121564 10 mg/Kg administered over 60 minutes given intravenously every 2 weeks for 4 doses plus chemotherapy depending on tumor histology.

Compound 121564

Arafat H Tfayli, MD

Taher Abu-Hejleh, MD

Fadi Karak, MD

Hady Ghanem, MD

Fadi Farhat, MD

The purpose of this study is to assess the response rate to neoadjuvant Compound 121564 plus platinum doublet chemotherapy in patients with early stage non-small cell lung cancer.

Open-label, single-arm multi-center phase II trial of neoadjuvant Compound 121564 plus platinum doublet chemotherapy conducted among patients with early stage (IB, II, IIIA) non-small cell lung cancer.

Neoadjuvant Compound 121564 Plus Platinum Doublet Chemotherapy in Non-Small Cell Lung Cancer

Phase II Trial of Neoadjuvant Compound 121564 Plus Platinum Doublet Chemotherapy in Non-Small Cell Lung Cancer

To assess the overall response rate (ORR) of patients receiving neoadjuvant Compound 121564 plus platinum doublet chemotherapy based on RECIST 1.1 criteria

To assess the pathologic complete response rate in patients receiving combination Compound 121564 and chemotherapy.

To assess the major pathologic response rate (\<10% viable tumor cells) in patients receiving combination Compound 121564 and chemotherapy.

To assess progression-free survival (PFS) at 1, 2 and 3 years in patients receiving a combination of Compound 121564 plus platinum doublet chemotherapy.

To assess overall survival (OS) in patients receiving a combination of Compound 121564 plus platinum doublet chemotherapy.

To compare the ORR in enrolled squamous vs. non-squamous lung cancer patients receiving the proposed treatment regimen.

To compare the PFS in enrolled squamous vs. non-squamous lung cancer patients receiving the proposed treatment regimen.

To compare the OS in enrolled squamous vs. non-squamous lung cancer patients receiving the proposed treatment regimen.

To assess patient-related outcomes in patients receiving a combination of Compound 121564 plus platinum doublet chemotherapy.

To assess the tolerability of the proposed treatment regimen in the cohort of patient enrolled.

To analyze as exploratory analysis the ORR in patients with 50% or more PD-L1 expression level vs. patients with less than 50% PD-L1 expression level receiving the proposed treatment regimen.

To analyze as exploratory analysis the PFS in patients with 50% or more PD-L1 expression level vs. patients with less than 50% PD-L1 expression level receiving the proposed treatment regimen.

To analyze as exploratory analysis the OS in patients with 50% or more PD-L1 expression level vs. patients with less than 50% PD-L1 expression level receiving the proposed treatment regimen.

Merck KGaA, Darmstadt, Germany

Phoenix Clinical Research

Arafat Tfayli

Professor of Clinical Medicine

Micronutrients

Hematinics

Vitamins

Nivolumab

Cisplatin

Ipilimumab

Tubulin Modulators

Antimitotic Agents

Immune Checkpoint Inhibitors

Folic Acid

Vitamin B Complex

Folic Acid Antagonists

Folinic Acid

Folate

Vitamin B9

Platinum Doublet Chemotherapy

Bristol-Myers Squibb

The purpose of part 1 of this study is to determine the objective response rate (ORR) in stage IV NSCLC subjects treated with nivolumab in combination with ipilimumab as first line therapy.

The purpose of part 2 of this study is to determine the safety and tolerability of nivolumab and ipilimumab combined with a short course of chemotherapy in first line stage IV NSCLC.

Nivolumab in Combination With Ipilimumab (Part 1); Nivolumab Plus Ipilimumab in Combination With Chemotherapy (Part 2) as First Line Therapy in Stage IV Non-Small Cell Lung Cancer

A Study of Nivolumab in Combination With Ipilimumab (Part 1); and Nivolumab Plus Ipilimumab in Combination With Chemotherapy (Part 2) as First Line Therapy in Stage IV Non-Small Cell Lung Cancer (NSCLC)

Objective response rate (ORR) in PD-L1 positive (PD-L1 ≥1%) and PD-L1 negative (PD-L1 \<1%) participants was defined as the percentage of treated participants with confirmed complete response (CR) or partial response (PR) per RECIST 1.1 based on Blinded Independent Central Review (BICR) assessment.

Dose limiting toxicities (DLTs) were defined as any of the items listed below.

1. Any Grade 2 drug-related uveitis or eye pain that does not respond to topical therapy and does not improve to Grade 1 severity within the re-treatment period OR requires systemic treatment.
2. Any Grade 2 drug-related pneumonitis or interstitial lung disease that does not resolve to dose delay and systemic steroids in 14 days.
3. Any Grade 3 non-skin drug-related adverse event with the exception of laboratory abnormalities that cannot be alleviated or controlled by appropriate care within 14 days.
4. Any Grade 4 drug-related adverse event including laboratory abnormalities except Grade 4 leukopenia or neutropenia lasting \< 14 days and asymptomatic amylase/lipase elevation.
5. Drug-related hepatic function laboratory abnormalities.

Number of participants with adverse events (AEs) including serious adverse events (SAEs) and deaths graded by Common Terminology Criteria for Adverse Events (CTCAE v4.0) to determine the safety and tolerability of Nivolumab and Ipilimumab combined with chemotherapy.

Number of participant with specific liver laboratory abnormalities graded by Common Terminology Criteria for Adverse Events (CTCAE v4.0) to determine the safety and tolerability of Nivolumab and Ipilimumab combined with chemotherapy.

Number of participants with specific thyroid laboratory abnormalities graded by Common Terminology Criteria for Adverse Events (CTCAE v4.0) to determine the safety and tolerability of Nivolumab and Ipilimumab combined with chemotherapy.

Overall survival (OS) was defined as the time from date of first treatment to the date of death due to any cause. A participant who has not died will be censored at the last known date alive.

Progression Free Survival (PFS) was defined as the time between the date of first dose and the first date of documented progression, as determined by blinded independent central review (BICR), or death due to any cause, whichever occurred first. Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.

Progression Free Survival (PFS) was defined as the time between the date of first dose and the first date of documented progression, as determined by investigator (per RECIST 1.1), or death due to any cause, whichever occurred first. Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.

Objective response rate (ORR) was defined as the percentage of treated participants with confirmed complete response (CR) or partial response (PR) per RECIST 1.1 based on Blinded Independent Central Review (BICR) assessment.

CR = Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \< 10 mm.

PR = At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.

Objective response rate (ORR) was defined as the percentage of treated participants with confirmed complete response (CR) or partial response (PR) per RECIST 1.1 based on investigator assessment.

CR = Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \< 10 mm.

PR = At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.

Overall survival (OS) by PD-L1 expression levels was defined as the time from date of first treatment to the date of death due to any cause. A participant who has not died will be censored at the last known date alive.

PD-L1 ≥1% = PD-L1 positive (membranous staining in ≥ 1% tumor cells) PD-L1 \<1% = PD-L1 negative (membranous staining in \<1% tumor cells)

Progression Free Survival (PFS) by PD-L1 expression levels was defined as the time between the date of first dose and the first date of documented progression, as determined by blinded independent central review (BICR), or death due to any cause, whichever occurred first. Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.

PD-L1 ≥1% = PD-L1 positive (membranous staining in ≥ 1% tumor cells) PD-L1 \<1% = PD-L1 negative (membranous staining in \<1% tumor cells)

Objective response rate (ORR) by PD-L1 expression levels was defined as the percentage of treated participants with confirmed complete response (CR) or partial response (PR) per RECIST 1.1 based on Blinded Independent Central Review (BICR) assessment.

CR = Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \< 10 mm.

PR = At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.

PD-L1 ≥1% = PD-L1 positive (membranous staining in ≥ 1% tumor cells) PD-L1 \<1% = PD-L1 negative (membranous staining in \<1% tumor cells)

Overall survival (OS) by tumor mutational burden (TMB) using DNA derived from tumor specimens was defined as the time from date of first treatment to the date of death due to any cause. A participant who has not died will be censored at the last known date alive.

High TMB = ≥ 10 mutations per megabase Low TMB = \< 10 mutations per megabase

Progression Free Survival (PFS) by tumor mutational burden (TMB) using DNA derived from tumor specimens was defined as the time between the date of first dose and the first date of documented progression, as determined by blinded independent central review (BICR), or death due to any cause, whichever occurred first. Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.

High TMB = ≥ 10 mutations per megabase Low TMB = \< 10 mutations per megabase

Objective response rate (ORR) by tumor mutational burden (TMB) using DNA derived from tumor specimens was defined as the percentage of treated participants with confirmed complete response (CR) or partial response (PR) per RECIST 1.1 based on Blinded Independent Central Review (BICR) assessment.

CR = Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \< 10 mm.

PR = At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.

High TMB = ≥ 10 mutations per megabase Low TMB = \< 10 mutations per megabase

Part 1 Nivolumab IV 3 mg/kg Q2W + Ipilimumab IV 1 mg/kg Q6W

Nivolumab+Ipilimumab

Part 2 Nivolumab IV 360mg Q3W + Ipilimumab IV 1 mg/kg Q6W + 2 cycles Platinum Doublet Chemotherapy

Nivolumab+Ipilimumab+Chemotherapy

Total

Age, Categorical

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

Bristol-Myers Squibb Study Director

PD-L1 ≥1%

PD-L1 <1%

Objective Response Rate (ORR) by PD-L1 Positive and Negative Levels - Part 1

Number of Participants With Dose Limiting Toxicities (DLTs) - Part 2

Adverse Events (AEs)

Serious Adverse Events (SAEs)

Deaths due to Disease progression

Deaths due to Study drug toxicity

Deaths due to unknown causes

Deaths due to other causes

Number of Participants With Adverse Events (AEs) - Part 2

ALT OR AST >3XULN

ALT OR AST >5XULN

ALT OR AST >10XULN

ALT OR AST >20XULN

TOTAL BILIRUBIN >2XULN

Concurrent ALT OR AST >3XULN & BILIRUBIN >2XULN within 1 day

Concurrent ALT OR AST >3XULN & BILIRUBIN >2XULN within 30 days

All treated participants with at least one on-treatment measurement of the corresponding laboratory parameter -Part 2

Number of Participants With Laboratory Abnormalities in Hepatic Tests - Part 2

TSH > ULN

TSH > ULN with TSH <= ULN at baseline

TSH > ULN with at least one FT3/FT4 test value < LLN

TSH > ULN with all other FT3/FT4 test values ≥ LLN

TSH > ULN with FT3/FT4 test missing

TSH < LLN

TSH < LLN with TSH >= LLN at baseline

TSH < LLN with at least one FT3/FT4 test value > ULN

TSH < LLN with all other FT3/FT4 test values <= ULN

TSH < LLN with FT3/Ft4 test missing

All treated participants with at least one on-treatment TSH measurement -Part 2

Number of Participants With Laboratory Abnormalities in Thyroid Tests - Part 2

Overall Survival (OS) - Part 1

Overall Survival (OS) - Part 2

Progression Free Survival (PFS) - Part 1

Progression Free Survival (PFS) - Part 2

Objective Response Rate (ORR) - Part 1

Objective Response Rate (ORR) - Part 2

All PD-L1 evaluable participants in Part 1. Data was pre-specified to be collected only in Part 1 arm

Overall Survival (OS) by PD-L1 Expression Levels - Part 1

Progression Free Survival (PFS) by PD-L1 Expression Levels - Part 1

Objective Response Rate (ORR) by PD-L1 Expression Levels-Part 1

High TMB (>=10 Mutations/MB)

Low TMB (<10 Mutations/MB)

All TMB evaluable participants in Part 1. Data was pre-specified to be collected only in Part 1 arm

Overall Survival (OS) by Tumor Mutation Burden (TMB) Levels - Part 1

Progression Free Survival (PFS) by Tumor Mutation Burden (TMB) Levels - Part 1

Objective Response Rate (ORR) by Tumor Mutation Burden (TMB) Levels - Part 1

Overall Study

Veliparib

Veliparib and nivolumab in combination with platinum doublet chemotherapy (carboplatin/paclitaxel or carboplatin/pemetrexed)

Veliparib in combination with platinum doublet chemotherapy (carboplatin/paclitaxel or carboplatin/pemetrexed)

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Randomized Trial Comparing Standard of Care Versus Immune- Based Combination in Relapsed Stage III Non-small-cell Lung Cancer (NSCLC) Pretreated With Chemoradiotherapy and Durvalumab	NCT05568212	Non-small-cell ...	Durvalumab Olaparib tablet Single-agent ch... Platinum double...	18 Years -	Fondazione Ricerca Traslazionale
Golidocitinib in Combination With Sintilimab for PD-L1 Selected Treatment Locally Advanced or Metastatic Non-Small Cell Lung Cancer(NSCLC)	NCT06198907	Non-Small-Cell ...	Golidocitinib Sintilimab platinum double...	18 Years - 75 Years	Cancer Institute and Hospital, Chinese Academy of Medical Sciences
Neoadjuvant Compound 121564 Plus Platinum Doublet Chemotherapy in Non-Small Cell Lung Cancer	NCT03480230	Non-Small Cell ...	Compound 121564	18 Years -	American University of Beirut Medical Center
Nivolumab in Combination With Ipilimumab (Part 1); Nivolumab Plus Ipilimumab in Combination With Chemotherapy (Part 2) as First Line Therapy in Stage IV Non-Small Cell Lung Cancer	NCT02659059	Non-Small-Cell ...	Nivolumab Ipilimumab Platinum Double...	18 Years -	Bristol-Myers Squibb
Study of Veliparib in Combination With Nivolumab and Platinum Doublet Chemotherapy in Participants With Metastatic or Advanced Non-Small Cell Lung Cancer (NSCLC)	NCT02944396	Non-Small Cell ...	pemetrexed nivolumab paclitaxel veliparib carboplatin	18 Years -	AbbVie

Spots Global Cancer Trial Database for platinum doublet chemotherapy