Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Carcinoma, Non-Small-Cell Lung

Lung Neoplasms

Carcinoma

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

Antineoplastic Agents

All Drugs and Chemicals

Paclitaxel

Carboplatin

Pembrolizumab

Docetaxel

Albumin-Bound Paclitaxel

Bemarituzumab

Tubulin Modulators

Antimitotic Agents

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Participants with SqNSCLC will receive escalating doses of bemarituzumab in combination with docetaxel.

Participants with SqNSCLC and FGFR2b overexpression will receive the dose of bemarituzumab in combination with docetaxel identified as safe during Part 1.

Participants with SqNSCLC and FGFR2b overexpression will receive bemarituzumab monotherapy.

Participants with FGFR2b overexpression will receive the dose of bemarituzumab identified as safe during Part 1 in combination with pembrolizumab, carboplatin and either paclitaxel or nab-paclitaxel.

Nab-paclitaxel

The primary objectives of this study are to evaluate the safety and tolerability of bemarituzumab monotherapy and combination with other anti-cancer therapies, and to determine the recommended phase 3 dose of bemarituzumab in combination with other anti-cancer therapies.

A Study of Bemarituzumab Monotherapy and Combination With Other Anti-cancer Therapy in SqNSCLC With FGFR2b Overexpression (FORTITUDE-201)

A Phase 1b Study Evaluating the Safety, Tolerability, Pharmacokinetics, and Efficacy of Bemarituzumab Monotherapy and Combination With Other Anti-Cancer Therapy in Subjects With Squamous-Cell Non-Small-Cell Lung Cancer (FORTITUDE-201)

De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request.

Adverse events (AEs) are defined as any untoward medical occurrence in a clinical study participant irrespective of a causal relationship with the study treatment. TEAEs are any event that occurs after the participant has received study treatment. Any clinically significant changes in vital signs, physical examinations, clinical laboratory tests, and visual acuity that occur after study treatment administration will be recorded as TEAEs.

Amgen

Digestive System Diseases

Gland and Hormone Related Diseases

Symptoms and General Pathology

Rare Diseases

Colorectal Neoplasms

Pancreatic Neoplasms

Carcinoma, Squamous Cell

Head and Neck Neoplasms

Neoplasm Metastasis

Squamous Cell Carcinoma of Head and Neck

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Gastrointestinal Neoplasms

Digestive System Neoplasms

Endocrine Gland Neoplasms

Gastrointestinal Diseases

Pancreatic Diseases

Endocrine System Diseases

Intestinal Neoplasms

Colonic Diseases

Intestinal Diseases

Rectal Diseases

Neoplasms, Squamous Cell

Pancreatic Cancer

Cisplatin

Tisotumab vedotin

Tisotumab Vedotin on Day 1 of every 21-day cycle in participants with various solid tumors in 2L+

Tisotumab Vedotin on Days 1, 8, and 15 of 28-day cycle in participants with various solid tumors in 2L+

Tisotumab Vedotin on Days 1 and 15 of every 28-day cycle in participants with HNSCC or sqNSCLC in 2L+

Tisotumab Vedotin + pembrolizumab + (carboplatin or cisplatin). Given on Day 1 of every 21-day cycle in participants with various solid tumors in 1L HNSCC or sqNSCLC

Tisotumab Vedotin on Days 1 and 15 of every 28-day cycle in participants with HNSCC in the second- or third-line setting

Tisotumab Vedotin + pembrolizumab. Tisotumab Vedotin given on Days 1, 15, and 29 of every 6-week cycle. Pembrolizumab given on Day 1 of every 6-week cycle in participants with HNSCC in the first line setting

Tisotumab Vedotin + pembrolizumab + carboplatin. Tisotumab Vedotin and carboplatin given on Days 1, 15, and 29 of every 6-week cycle. Pembrolizumab given on Day 1 of every 6-week cycle in participants with HNSCC in the first line setting

tisotumab vedotin

pembrolizumab

AUC 5mg/mL per minute or AUC 3.3mg/mL per minute given by IV

carboplatin

cisplatin

Seagen Trial Information Support

Assuntina Gesualda Sacco, MD

Brenda Hann

Heather Wakelee, M.D.

Jennifer Saller

Steven R Schuster

Daniela Skiff

Thomas George

Alaa Taha

Christine Chung

Briana Porwisz

Jochen Lorch, MD

Ari Rosenberg, MD

Cindy Stoner

Bert H O'Neil

Jane Lindsay Godbey

John Hamm

Vaishnavi "Vaishu" Bandaru

Tanguy Y Seiwert

Ammar Sukari

Douglas Adkins, MD

Lara Dunn, MD

Emmie Cole

Shetal Patel

Deonna Asbury

Lowell L Hart

Jeremy Cetnar

Lova Sun

Jimmy Rodrigues

Howard Safran

Guermarie Velazquez-Torres

Neal S. Akhave

Sonia Salas

Isaac Tafur

Cristina P Rodriguez

Neil Chua

Christophe Borg

Sebastien Salas

Claude El Kouri, MD

Jaafar Bennouna

Caroline Even

Christian Meyer

Alfredo Berruti

Pierfrancesco Tassone, MD

Giuseppe Curigliano

Fortunato Ciardiello

Mauro Iannopollo, MD

Claudia Casanova

Maria Garcia Pallas, MD

Beatriz Cirauqui

Alejandro Martinez

Irene Brana

Teresa Alonso Gordoa

Silvia Catot Tort, MD

Juan Coves Sarto

Medical Monitor

This trial will study tisotumab vedotin to find out whether it is an effective treatment alone or with other anticancer drugs for certain solid tumors and what side effects (unwanted effects) may occur. There are seven parts to this study.

* In Part A, the treatment will be given to participants every 3 weeks (3-week cycles).
* In Part B, participants will receive tisotumab vedotin on Days 1, 8, and 15 every 4-week cycle.
* In Part C, participants will receive tisotumab vedotin on Days 1 and 15 of every 4-week cycle.
* In Part D, participants will be given treatment on Day 1 of every 3-week cycle. Participants in Part D will get tisotumab vedotin with either:

  * Pembrolizumab or,
  * Pembrolizumab and carboplatin, or
  * Pembrolizumab and cisplatin
* In Part E, participants will receive tisotumab vedotin on Days 1 and 15 of every 4-week cycle.
* In Part F, participants will receive tisotumab vedotin on Days 1, 15, and 29 of every 6-week cycle. Participants in Part F will get tisotumab vedotin with pembrolizumab.
* In Part G, participants will receive tisotumab vedotin on Days 1, 15, and 29 of every 6-week cycle. Participants in Part G will get tisotumab vedotin with pembrolizumab and carboplatin.

The primary goal of this trial is to assess the activity, safety, and tolerability of tisotumab vedotin for the treatment of selected solid tumors. Patients will be treated with single agent tisotumab vedotin or tisotumab vedotin in combination with other anticancer agents. Patients who meet eligibility criteria will be enrolled into cohorts based on tumor type. Tumor types to be evaluated include colorectal cancer, squamous non-small cell lung cancer (sqNSCLC), exocrine pancreatic adenocarcinoma, and head and neck squamous cell carcinoma (HNSCC).

Efficacy and Safety Study of Tisotumab Vedotin for Patients With Solid Tumors

Open Label Phase 2 Study of Tisotumab Vedotin for Locally Advanced or Metastatic Disease in Solid Tumors

Proportion of patients who achieve a confirmed complete response (CR) or partial response (PR) according to RECIST v1.1 as assessed by the investigator

Proportion of patients who achieve a confirmed CR or PR according to RECIST v1.1 as assessed by BICR

Type, severity, and relatedness of adverse events. An AE is any untoward medical occurrence in a subject or clinical investigational subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment.

Proportion of patients who achieve a CR or PR according to RECIST v1.1 as assessed by the investigator

Proportion of patients who achieve a CR or PR according to RECIST v1.1 as assessed by BICR

Proportion of patients who achieve a confirmed CR or PR according to RECIST v1.1 as assessed by the investigator, or meet the stable disease (SD) criteria at least once after start of study treatment at a minimum interval of 12 weeks

Proportion of patients who achieve a confirmed CR or PR according to RECIST v1.1 as assessed by BICR, or meet the stable disease (SD) criteria at least once after start of study treatment at a minimum interval of 12 weeks

Time from the first documentation of objective response to the first documentation of PD or death due to any cause, whichever comes first, as assessed by the investigator

Time from the first documentation of objective response to the first documentation of PD or death due to any cause, whichever comes first, as assessed by BICR

Time from the start of study treatment to the first documentation of objective response, as assessed by investigator

Time from the start of study treatment to the first documentation of objective response, as assessed by BICR

Time from the start of study treatment to the first documentation of PD according to RECIST v1.1 or death due to any cause, whichever comes first, as assessed by the investigator

Time from the start of study treatment to the first documentation of PD according to RECIST v1.1 or death due to any cause, whichever comes first, as assessed by BICR

Time from the start of study treatment to date of death due to any cause

Observed plasma concentration at the end of the dosing interval

Genmab

Merck Sharp & Dohme LLC

Seagen Inc.

Antibodies

Antibodies, Monoclonal

Cetuximab

Immunoglobulins

Immunoglobulin G

Mitogens

Immunoglobulins, Intravenous

All participants receive HMBD-001 with docetaxel

All participants receive HMBD-001 with docetaxel plus cetuximab

HMBD-001 is a humanized Immunoglobulin G1 (IgG1) anti-Human Epidermal Growth Factor Receptor 3(HER3) monoclonal antibody (mAb). It is administered intravenously (IV) weekly

HMBD-001

Docetaxel 75 mg/m\^2 IV once every 3 weeks

Cetuximab 400 mg/m\^2 IV loading dose, followed by 250 mg/m\^2 weekly

Kon Yew Kwek, BMBCh, DPhil

Nick Pavlakis

Vladimir Andelkovic

Ganessan Kichenadasse

Vinod Ganju

Vinod Prof Ganju

Gary Richardson

Samantha Bowyer

Aaron Tan

Jens Samol

This is a phase 1b multi-center, open-label study of HMBD-001 in combination with docetaxel with or without cetuximab in participants with locally advanced or metastatic squamous Non-Small Cell Lung Cancers

Study of an Anti-HER3 Antibody, HMBD-001, With Docetaxel +/- Cetuximab in Advanced Squamous Non-small Cell Lung Cancers

A Phase 1b Study to Evaluate HMBD-001 in Combination With Docetaxel With or Without Cetuximab in Participants With Advanced Squamous Non-small Cell Lung Cancers

An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product temporally associated with the use of study treatment, whether or not considered to be related to the study treatment

DLTs will be assessed during the safety run-in phase and are defined as toxicities that meet pre-defined severity criteria and assessed as having a suspected relationship to study drug, and unrelated to disease, disease progression, intercurrent illness, or concomitant medications that occurs within the first cycle (3 weeks) of treatment

The ORR is defined as the proportion of subjects with confirmed Complete Response (CR) or confirmed Partial Response (PR), based on RECIST Version 1.1

Merck KGaA, Darmstadt, Germany

Hummingbird Bioscience

Cohort 1: Activating (high confidence) FGFR translocations (max. 15 patients) under daily Erdaifitinib treatment

Cohort 2: Activating (high confidence) hotspot FGFR mutations (max. 15 patients) under daily Erdafitinib treatment

Cohort 3: Activating (low confidence) FGFR alteration (max. 20 patients)

ERDAFITINIB

Lucia Nogova, MD

In the FIND trial, Non Small Cell Lung Carcinoma (NSCLC) patients with Fibroblast Growth Factor Receptor (FGFR) genetic alteration will be treated with the selective FGFR1-4 inhibitor erdafitinib. Archival samples, fresh frozen tumor samples and blood for circulating tumor DNA (ctDNA) will be collected before treatment. Patients will be treated until disease progression or unacceptable toxicity. In case of progression, fresh frozen tumor biopsies and ctDNA analyses will be performed to assess resistance mechanisms. The primary objective of the trial is to analyze the efficacy of erdafitinib in NSCLC patients with FGFR genetic alterations. NSCLC patient number will be based on a statistical hypothesis aiming at increasing the response rate comparing to chemotherapy/immunotherapy after standard treatment.

Downstream signaling of fibroblast growth factor receptors 1-4 (FGFR 1-4) regulates cell proliferation, migration, differentiation and survival in healthy cells. Genetic alterations (amplifications, point-mutations and translocations) in FGFR1-4 genes cause altered signaling and oncogenic transformation. FGFR-alterations with sensitivity to kinase inhibition have been identified in a variety of tumors such as breast-, bladder- and endometrial-cancer, squamous cell lung and head and neck cancer, cholangiocarcinoma and glioblastoma.

First-in-man/phase-I clinical trials with erdafitinib and BGJ398 - both selective FGFR inhibitors - enrolled patients with any genetic alterations in FGFR. The trials showed clinical responses with differences according to the type of FGFR alterations and histological subtypes. In the BGJ398 trial, the partial response rate was 11% (4/36) in patients with FGFR1 amplified squamous NSCLC (sqNSCLC) and 38% (3/8) in patients with FGFR3-mutant bladder cancer. No PR was observed in patients with FGFR1/2 amplified (n=25) and FGFR3 mutant (n=1) breast cancer. All patients with FGFR2-translocated (n=2) and FGFR2-mutated cholangiocarcinoma (n=1) showed reduced tumor burden of 20% and 10%, respectively. In the erdafitinib trial, 5 partial responses were seen in FGFR translocated tumors: 3/8 (37.5%) patients with urothelial carcinoma, 1/3 (33%) patients with glioblastoma and 1 patient with endometrial cancer reached PR. Summing up the results of the phase-I trials, the inhibition of FGFR downstream pathways in FGFR translocated and mutated solid tumors exerted clinical activity. Thus, focusing treatment with FGFR inhibitors on FGFR mutated and translocated solid tumors may increase response rates, progression free and overall survival in these tumors with otherwise adverse prognosis.

In NSCLC patients without druggable alterations in genes as EGFR, ALK or ROS1 and without high PD-L1 (Programmed cell death 1 ligand 1) expression, prognosis remains adverse with a median survival time of about 18 months. Particularly in sqNSCLC, only few driver mutations have been identified yet. Of these, solely mutations of the KRAS gene (although observed at low frequency in sqNSCLC) were explored in large clinical studies targeting KRAS downstream signaling with no survival benefit comparing to chemotherapy. Immunotherapy with PD-1 antibodies such as nivolumab and pembrolizumab showed benefit in patients with high PD-L1 expression mainly.

The frequency of somatic FGFR1-3 mutations in lung cancer is about 4% (Helsten et al., 2016). Translocations occur with a similar frequency of about 4% in lung cancer. Multiple of these FGFR alterations are shown to have oncogenic potential as demonstrated in multiple in vitro, in vivo and first-in-man studies.

Preclinical models in NSCLC cell lines and xenografts showed oncogenic activity of FGFR2/3 mutations with consecutive sensitivity to FGFR inhibitors. Similarly, FGFR3-TACC translocation exerted kinase activation in sqNSCLC cell lines and other tumor types. Furthermore, patient derived FGFR3-fusion lung xenograft model showed responses to FGFR targeted treatment.

In summary, on the basis of genetically and phenotypically validated cell-line panels, in vivo and particularly on the basis of clinical data, there is strong evidence for a clinical benefit from FGFR inhibition for patients with FGFR altered NSCLC.

The primary objective of the trial is to analyze the efficacy of erdafitinib in NSCLC patients with FGFR genetic alterations. NSCLC patient number will be based on a statistical hypothesis aiming at increasing the response rate comparing to chemotherapy/immunotherapy after standard treatment.

Patients with NSCLC and FGFR alteration with high evidence on oncogenic transformation according to FIND molecular board will be included to cohort 1 (FGFR translocated NSCLC patients) and cohort 2 (FGFR mutated NSCLC patients). Patients with NSCLC and FGFR alterations without enough evidence (intermediate / low evidence according to FIND molecular tumor board) for recruitment into cohorts 1 or 2, will be treated in cohort 3. Overall response rate under Erdafitinib treatment will be the primary endpoint.

FGFR Inhibitor in FGFR Dysregulated Cancer

A Phase II Trial to Evaluate Efficacy and Safety of Erdafitinib in Patients With Advanced Non Small Cell Lung Carcinoma (NSCLC) Harboring Fibroblast Growth Factor Receptor (FGFR) Genetic Alterations After Relapse of Standard Therapy.

Overall response rate (ORR) per RECIST 1.1 under erdafitinib treatment in sqNSCLC with genetic alteration in FGFR

assessment of adverse events according to CTC-AE

Lung Cancer Group Cologne

sapanisertib

Bradley J Sumrow, MD

This is a multicenter, randomized, open-label Phase 2 study of sapanisertib in biomarker-defined populations of sqNSCLC. Patients with NFE2L2 (the name for gene encoding the protein called NRF2)-mutated or wild-type sqNSCLC should have disease that has progressed on or after at least two prior systemic therapies for metastatic disease including platinum-doublet chemotherapy and a programmed cell death 1 ligand 1 (PD-L1) inhibitor. The study will evaluate sapanisertib monotherapy in patients with relapsed/refractory sqNSCLC as two separate groups: Group A: NFE2L2-mutated sqNSCLC and Group B: NFE2L2-WT sqNSCLC.

NFE2L2 mutation status for all patients will be identified using local or central next generation sequencing (NGS) testing on archival or fresh tissue or circulating tumor deoxyribonucleic acid (ctDNA), the results of which must be reviewed and approved by the Sponsor prior to enrollment. Each group will be randomized 1:1 to one of two doses/schedules of sapanisertib. Approximately 30 NFE2L2-mutant and 20 NFE2L2-wild type patients will be enrolled. Patients will be treated with sapanisertib until disease progression per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1), unacceptable toxicity, withdrawal of consent, or death.

2 dosing schedules: 3 mg once per day (3 mg total) OR 2 mg twice per day (4 mg total)

Group A: 30 participants randomized 1:1 to one of two dosing schedules

Group B: approximately 20 participants randomized 1:1 to one of two dosing schedules

A Study of Sapanisertib in Relapsed/Refractory NFE2L2-Mutated and Wild-Type Squamous Non-Small Cell Lung Cancer

A Randomized, Open-Label Phase 2 Study of the TORC 1/2 Inhibitor Sapanisertib in Relapsed/Refractory NFE2L2 (NRF2)-Mutated and Wild-Type (WT) Squamous Non-Small Cell Lung Cancer (sqNSCLC)

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Study of Bemarituzumab Monotherapy and Combination With Other Anti-cancer Therapy in SqNSCLC With FGFR2b Overexpression (FORTITUDE-201)	NCT05267470	Squamous-Cell N...	Bemarituzumab Docetaxel Pembrolizumab Carboplatin Paclitaxel Nab-paclitaxel	18 Years - 99 Years	Amgen
Efficacy and Safety Study of Tisotumab Vedotin for Patients With Solid Tumors	NCT03485209	Colorectal Neop... Carcinoma, Non-... Exocrine Pancre... Carcinoma, Squa...	tisotumab vedot... pembrolizumab carboplatin cisplatin	18 Years -	Seagen Inc.
A Study of Bemarituzumab Monotherapy and Combination With Other Anti-cancer Therapy in SqNSCLC With FGFR2b Overexpression (FORTITUDE-201)	NCT05267470	Squamous-Cell N...	Bemarituzumab Docetaxel Pembrolizumab Carboplatin Paclitaxel Nab-paclitaxel	18 Years - 99 Years	Amgen
Study of an Anti-HER3 Antibody, HMBD-001, With Docetaxel +/- Cetuximab in Advanced Squamous Non-small Cell Lung Cancers	NCT05910827	Advanced or Met...	HMBD-001 Docetaxel Cetuximab	18 Years -	Hummingbird Bioscience
FGFR Inhibitor in FGFR Dysregulated Cancer	NCT03827850	Lung Cancer NSCLC Pulmonary Neopl... Squamous Cell L... NSCLC Stage IV	ERDAFITINIB	18 Years -	Lung Cancer Group Cologne
FGFR Inhibitor in FGFR Dysregulated Cancer	NCT03827850	Lung Cancer NSCLC Pulmonary Neopl... Squamous Cell L... NSCLC Stage IV	ERDAFITINIB	18 Years -	Lung Cancer Group Cologne
A Study of Sapanisertib in Relapsed/Refractory NFE2L2-Mutated and Wild-Type Squamous Non-Small Cell Lung Cancer	NCT05275673	Non-Small Cell ... Squamous Non-sm... Squamous Non-Sm... NFE2L2 Gene Mut...	sapanisertib	18 Years -	Calithera Biosciences, Inc

Spots Global Cancer Trial Database for sqnsclc

Every month we try and update this database with for sqnsclc cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for sqnsclc

Every month we try and update this database with for sqnsclc cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for sqnsclc cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.