Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Carcinoma, Non-Small-Cell Lung

Lung Neoplasms

Carcinoma

Carcinoma, Bronchogenic

Bronchial Neoplasms

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Antineoplastic Agents

All Drugs and Chemicals

Antiemetics

Gastrointestinal Agents

Anti-Allergic Agents

Central Nervous System Depressants

Dermatologic Agents

Paclitaxel

Albumin-Bound Paclitaxel

Carboplatin

Durvalumab

Diphenhydramine

Promethazine

Histamine H2 Antagonists

Serotonin

Tubulin Modulators

Antimitotic Agents

Antineoplastic Agents, Immunological

Participants in Device Duration Level 1 will receive Tumor Treatment Fields (TTF) therapy during standard of care consolidation durvalumab.

Participants in in Device Duration Level 2 will begin TTF therapy during SOC durvalumab and SOC Concurrent chemoradiation following Device Duration Level 1.

Concurrent chemoradiation will be given per standard of care within 24 hours of initiation of standard of care radiation therapy. Treatment will include a paclitaxel/carboplatin chemotherapy regimen administered during the radiotherapy course (over 6-7 weeks).

Paclitaxel (50 mg/m2) will be administered intravenous over 1 hour followed by Carboplatin AUC = 2 mg/min/mL intravenous weekly (every 7 days ± 3 days) during radiotherapy 11, NCCN Non-small cell lung cancer guidelines 2023).

If a patient has a hypersensitivity reaction to weekly paclitaxel, weekly nab-paclitaxel is allowed to replace paclitaxel at the discretion of the treating medical oncologist 37. The recommended starting dose of weekly nab-paclitaxel is 40 mg/m2 to 50 mg/m2 38 39. Standard premedications with steroids, diphenhydramine, H2 receptor antagonist, and 5-HT3 receptor antagonist antiemetics must be administered per individual institutional guidelines.

carboplatin chemotherapy

The NovoTTF-200T (TTFields) System is an investigational medical device delivering 150 kHz TTFields to the thorax for the treatment of patients at the age of 22 years or older. The device is a portable, battery operated system which delivers TTFields at 150 kHz to the thorax by means of insulated Transducer Arrays. The NovoTTF-200T produces electric forces intended to disrupt cancer cell division.

TTFields at 150 kHz to the thorax will be continuous for at least 11 hours a day on average, with a recommended duration of at least 18 hours a day. Subjects may take breaks for personal needs (e.g. showering, array exchange). TTFields may be continued as long as there is no disease progression per RECIST 1.1 or any of the treatment discontinuation conditions for subject withdrawal or termination.

NovoTTF-200T (TTFields) System

Consolidation Durvalumab will be given per standard of care and institutional guidelines every 4 weeks for up to 12 cycles. Refer to package insert for detailed pharmacologic, dosing, and safety information.

kaitlin Stephens

Wallace Akerley, MD

Kaitlin Stephens

The goal of this open-label, Phase 1 clinical trial is to determine the safety of TTFields started concurrently with SOC chemoradiation and during consolidation durvalumab in locally advanced, unresectable stage III non-small cell lung cancer (NSCLC). The main question it aims to answer is, "What is the rate of dose-limiting toxicities (DLTs) with TTFields in addition to concurrent chemoradiation and consolidation durvalumab?"

Step 1

* All participants will be screened and enrolled in Step 1 prior to SOC concurrent chemoradiation.
* The purpose of the Step 1 Registration is to ensure that eligible participants are candidate for concurrent chemoradiation and do not have contraindications to TTF therapy or immunotherapy.

  * Starting Level: Participants in Device Duration Level 1 will receive standard of care concurrent chemoradiation following Step 1 Registration.
  * Escalation Level : Participants in Device Duration Level 2 will begin standard of care chemoradiation and treatment with TTFields following Step 1 Registration.

Step 2

* All participants will complete Step 2 screening and enrollment prior to receiving treatment with durvalumab consolidation therapy and TTFields.
* The purpose of the Step 2 registration is to ensure that eligible patients meet criteria for consolidation durvalumab after completion of CRT and do not have contraindications to TTF. therapy or immunotherapy.

Tumor Treating Fields for Locally Advanced NSCLC

A Feasibility Study to Evaluate the Addition of Tumor Treating Fields to Treatment of Locally Advanced Stage III NSCLC

To assess the safety of Tumor Treating Fields (TTFields) started concurrently with SOC chemoradiation and during consolidation durvalumab for treatment of unresectable stage III non-small cell lung cancer (NSCLC).

To assess the safety and tolerability of TTFields started concurrently with SOC chemoradiation and during consolidation Durvalumab for treatment of unresectable stage III NSCLC.

To assess progression-free survival (PFS)

To assess overall survival (OS) in this study population

University of Utah

Micronutrients

Anti-Inflammatory Agents

Hematinics

Vitamins

Amino Acids

Pembrolizumab

Dexamethasone

Pemetrexed

Immunomodulating Agents

Dexamethasone acetate

Folic Acid

Vitamin B Complex

Vitamin B 12

Hydroxocobalamin

Trace Elements

Glucocorticoids

Hormones

Hormone Antagonists

Antineoplastic Agents, Hormonal

Immune Checkpoint Inhibitors

Enzyme Inhibitors

Folic Acid Antagonists

Folinic Acid

Methylcobalamin

Folate

Vitamin B9

Vitamin B12

Cobalamin

Cyanocobalamin

Glutamine

The glutaminase inhibitor telaglenastat will be administered orally, twice daily with food, every day in combination with standard-of-care pembrolizumab plus chemotherapy by intravenous (IV) infusion every 3 weeks.

Placebo will be administered orally twice daily with food every day in combination with standard-of-care pembrolizumab plus chemotherapy by IV infusion every 3 weeks.

Telaglenastat

Carboplatin Chemotherapy

Pemetrexed Chemotherapy

Pembrolizumab Immunotherapy

Placebo

Orally, once daily beginning 7 days prior to the first dose of pemetrexed and continue until 21 days after the last dose of pemetrexed.

Folic acid 400 -1000 μg

Vitamin B12 1000 μg Intramuscular injection one week prior to the first dose of pemetrexed and once every 3 cycles (9 weeks) thereafter. Subsequent vitamin B12 injections may be given the same day as pemetrexed administration.

Vitamin B12 1000 μg

For prophylaxis, orally twice per day (or equivalent). Taken the day before, day of, and day after pemetrexed administration.

Dexamethasone 4 mg

Emil Kuriakose, MD

This is a Phase 2, randomized, multicenter, double-blind study of the glutaminase inhibitor telaglenastat with standard-of-care pembrolizumab and chemotherapy versus placebo with standard-of-care pembrolizumab and chemotherapy for first line treatment of metastatic disease in patients with KEAP1/NRF2-mutated, stage IV, nonsquamous, non-small cell lung cancer (NSCLC). The study primary endpoints are PFS per RECIST v. 1.1 and safety. KEAP1/NRF2 mutation status (for eligibility) and STK11/LKB1 status (for stratification) will be determined by next generation sequencing. A commercial liquid biopsy (circulating tumor DNA) NGS test will be provided to study participants free of charge.

KEAPSAKE: A Study of Telaglenastat (CB-839) With Standard-of-Care Chemoimmunotherapy in 1L KEAP1/NRF2-Mutated, Nonsquamous NSCLC

A Phase 2 Randomized, Multicenter, Double-Blind Study of the Glutaminase Inhibitor Telaglenastat With Pembrolizumab and Chemotherapy Versus Placebo With Pembrolizumab and Chemotherapy in First-Line, Metastatic KEAP1/NRF2-Mutated, Nonsquamous, Non-Small Cell Lung Cancer (NSCLC)

Duration of investigator-determined PFS per RECIST v1.1 in the intent-to-treat (ITT) population

ORR is defined as the percentage of patients with complete response (CR) or partial response (PR) according to the RECIST v1.1 criteria as assessed by the investigator.

DOR is defined as the duration of response for patients achieving a CR or PR

Calithera Biosciences, Inc

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Tumor Treating Fields for Locally Advanced NSCLC	NCT06124118	Non Small Cell ...	carboplatin che... NovoTTF-200T (T... Durvalumab	22 Years -	University of Utah
KEAPSAKE: A Study of Telaglenastat (CB-839) With Standard-of-Care Chemoimmunotherapy in 1L KEAP1/NRF2-Mutated, Nonsquamous NSCLC	NCT04265534	Non-Small Cell ... Non-squamous No... Non-Squamous No... KEAP1 Gene Muta... NRF2 Gene Mutat... NFE2L2 Gene Mut...	Telaglenastat Carboplatin Che... Pemetrexed Chem... Pembrolizumab I... Placebo Folic acid 400 ... Vitamin B12 100... Dexamethasone 4...	18 Years -	Calithera Biosciences, Inc
KEAPSAKE: A Study of Telaglenastat (CB-839) With Standard-of-Care Chemoimmunotherapy in 1L KEAP1/NRF2-Mutated, Nonsquamous NSCLC	NCT04265534	Non-Small Cell ... Non-squamous No... Non-Squamous No... KEAP1 Gene Muta... NRF2 Gene Mutat... NFE2L2 Gene Mut...	Telaglenastat Carboplatin Che... Pemetrexed Chem... Pembrolizumab I... Placebo Folic acid 400 ... Vitamin B12 100... Dexamethasone 4...	18 Years -	Calithera Biosciences, Inc
Tumor Treating Fields for Locally Advanced NSCLC	NCT06124118	Non Small Cell ...	carboplatin che... NovoTTF-200T (T... Durvalumab	22 Years -	University of Utah

Spots Global Cancer Trial Database for carboplatin chemotherapy