Neoplasms

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Biliary Tract Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Biliary Tract Diseases

Gastrointestinal Diseases

Biliary Tract Cancer

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Pemetrexed

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D1 Pemetrexed 500 mg/m2 IV+ D1-21 Erlotinib 100mg once daily

Pemetrexed 500 MG

Erlotinib

seungtea kim, M.D. Ph.D

seungtae kim, MD,PhD

seungtae Kim, M.D., Ph.D

seungtea kim

Pemetrexed in combination with erlotinib as a salvage treatment in patients with metastatic biliary tract cancer (BTC) who failed gemcitabine containing chemotherapy

Biliary tract carcinoma (BTC) is rare in the Europe and the United States, but not uncommon in Asia and Latin America. The tumor arises from the ductular epithelium of the biliary tree within the liver (intrahepatic), the extrahepatic ducts (extrahepatic), or the gallbladder. Intrahepatic cancer is steadily increasing in the Western world. BTCs carry a poor prognosis with 1-year survival rate of 25%. Although surgery remains the only curative treatment for BTC, most patients present with advanced disease and die within a few months of diagnosis. While a combination of gemcitabine and platinum agents seems to be a conclusive treatment option as first-line treatment until now, the role or the optimal regimen for second-line treatment has not been established.

Pemetrexed, a multitarget antifolate which inhibits thymidylate synthase, dihydrofolate reductase and glycinamide ribonucleotide formyltransferase, was approved for the treatment of lung cancer and mesothelioma. In addition to its therapeutic efficacy, pemetrexed has tolerable safety profile and is considered as important therapeutic option for patients of poor performance statue or older age. Pemetrexed was studied in combination with gemcitabine in BTC patients and needs further research in BTC patients. Erlotinib is EGFR tyrosine kinase inhibitor. In BTC and pancreatic cancer, erlotinib showed prolonged survival in combination with chemotherapy. Moreover, the addition of erlotinib to gemcitabine and oxaliplatin showed antitumour activity in our previous phase III trial. And combination of pemetrexed and erlotinib showed tolerable safety profile in lung cancer trial.

So we plan this study to evaluate the efficacy and safety of pemetrexed in combination with erlotinib as a second line treatment in biliary tract cancer

Pemetrexed in Combination With Erlotinib as a Salvage Treatment in Patients With Metastatic Biliary Tract Cancer (BTC) Who Failed Gemcitabine Containing Chemotherapy: A Phase II Single Arm Prospective Study

SAMSUNG MEDICAL CENTER

Samsung Medical Center

Symptoms and General Pathology

Respiratory Tract (Lung and Bronchial) Diseases

Recurrence

Carcinoma, Non-Small-Cell Lung

Lung Neoplasms

Carcinoma

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

Antibodies

Antibodies, Bispecific

Immunoglobulins

Mitogens

Immunoglobulins, Intravenous

Lazertinib

Amivantamab-vmjw

Antineoplastic Agents, Immunological

Cysteine

Serine

Threonine

Methionine

CYCLE 1 (21-day cycle)

Amivantamab 1400 mg (1750 mg if body weight is \>80 kg) IV once weekly + Lazertinib 240 mg po daily + Pemetrexed 500 mg/m² IV on day 1

CYCLE 2 (21-day cycle)

Amivantamab 1400 mg (1750 mg if body weight is \>80 kg) IV on day 1 + Lazertinib 240 mg po daily + Pemetrexed 500 mg/m² IV on day 1

MAINTENANCE CYCLES 3 + (21-day cycle)

Amivantamab 1750 mg (2100 mg if body weight is \>80 kg) IV on day 1 + Lazertinib 240 mg po daily + Pemetrexed 500 mg/m² IV on day 1

Low fucose, fully human immunoglobulin gamma-1-based bispecific antibody directed against EGFR and MET tyrosine kinase receptors. It shows clinical activity against tumors with the primary activating EGFR mutations Exon 19del or Exon 21 L858R substitution, EGFR Exon 20ins mutations, the EGFR resistance mutations Threonine790Methionine (T790M) or Cysteine797Serine (C797S), and activation of the Mesenchymal Epithelial Transition (MET) pathway.

Amivantamab

It selectively inhibits both primary activating EGFR mutations (Exon 19del, Exon 21 L858R substitution) and the EGFR T790M resistance mutation, while having less activity versus wild-type EGFR.

Inhibits enzymes involved in folate-dependent metabolism, thereby disrupting cellular replication.

Pemetrexed 500 mg

Giana Corssac

Laura Voelcker

Tamizia Severo

Eduardo Henrique Cronemberger Costa e Silva

Narelle de Jesus

Sabina Bandeira Aleixo

Thais Abreu de Almeida

Janielle Ferreira

Sulene Cunha Sousa Oliveira

Letícia Mariana

Manuela Zereu

Tasiana Simonetti

Ana Caroline Zimmer Gelatti

Jéssica Frutuozo

Flávio Augusto Ferreira da Silva

Pamella Queluz

Tatiane Cardoso Motta

Natália Gonzalez

Káthia Cristina Abdalla

Luiz Henrique de Lima Araújo

Thaiza Lombardo

Pedro De Marchi

Marlene Salgado

Gilberto de Castro Júnior

Ligia Silva

William Nassib William Junior

Daniele Bracale

Felipe José Silva Melo Cruz

This is a phase II, single-arm, multicenter trial, conducted through Latin American Coorperative Oncology Group (LACOG). Treatment-naïve patients with recurrent/metastatic NSCLCs harboring EGFR exon 19 deletions or exon 21 L858R point mutations will be enrolled. At baseline, an archival or (optional) new tissue sample will be obtained for biomarker evaluation, as well as liquid biopsies. Treatment will continue until disease progression or unacceptable toxicity.

This study aims to test the hypothesis that delivery of maximum therapy consisting of lazertinib plus amivantamab plus chemotherapy as frontline treatment in patients with recurrent/metastatic NSCLC with EGFR exon 19 or exon 21 mutations will be feasible, safe, and will improve PFS compared to historical controls. If successful, this study may allow for the estimation of efficacy and toxicity of a three drug regimen of amivantamab, lazertinib, and pemetrexed and may support further evaluation of maximum therapy against osimertinib single agent, lazertinib single agent, osimertinib plus chemotherapy, and/or lazertinib plus amivantamab.

Amivantamab, Lazertinib, and Pemetrexed for First-line Treatment of Recurrent/Metastatic Non-small Cell Lung Cancers With Epidermal Growth Factor Receptor Mutations

A Single Arm, Phase 2 Study of Amivantamab, Lazertinib and Pemetrexed for First-line Treatment of Recurrent/Metastatic Non-small Cell Lung Cancers (NSCLCs) With EGFR Mutations

To evaluate the 18-month progression-free survival (PFS) rate of amivantamab, lazertinib, carboplatin and pemetrexed for first-line treatment of recurrent / metastatic non-small cell lung cancers (NSCLCs) with EGFR mutations.

Defined as the proportion of complete response (CR) or partial response (PR) according to RECIST v1.1.

Overall survival is defined as the time from the date of enrollment to the date of participant's death due to any cause.

The PFS 2 is defined as the time from enrollment until the date of second objective disease progression, after initiation of subsequent anticancer therapy, based on investigator assessment (after that used for PFS) or death, whichever comes first.

Safety includes adverse events in terms of treatment-emergent adverse events (AE). The rate of any grade of adverse events as well as the rate of adverse events grade ≥3 according to the CTCAE version 5 will be evaluated. Adverse events of special interest of Amivantamab and Lazertinib will be based on the definitions given in the protocol of each one.

Includes number of patients whose treatment had to be reduced, delayed, or permanently discontinued, grouped by reason. The reason for termination includes aspects of efficacy (e.g. termination due to tumor progression), safety (e.g. termination due to adverse events) and compliance (e.g. termination due to patient's withdrawal of consent).

Description of therapies after disease progression.

Defined as the change from baseline of disease-related symptoms and quality of life based on European Organization for Research and Treatment of Cancer (EORTC) core cancer instrument and supplemental lung cancer module.

Intracranial PFS is defined as the time from enrollment until the date of objective intracranial disease progression or death, whichever comes first, using RECIST v1.1.

Janssen, LP

Latin American Cooperative Oncology Group

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Pemetrexed in Combination With Erlotinib as a Salvage Treatment in Patients With Metastatic Biliary Tract Cancer (BTC) Who Failed Gemcitabine Containing Chemotherapy: A Phase II Single Arm Prospective Study	NCT03110484	Biliary Tract C...	Pemetrexed 500 ... Erlotinib	20 Years -	Samsung Medical Center
Pemetrexed in Combination With Erlotinib as a Salvage Treatment in Patients With Metastatic Biliary Tract Cancer (BTC) Who Failed Gemcitabine Containing Chemotherapy: A Phase II Single Arm Prospective Study	NCT03110484	Biliary Tract C...	Pemetrexed 500 ... Erlotinib	20 Years -	Samsung Medical Center
Amivantamab, Lazertinib, and Pemetrexed for First-line Treatment of Recurrent/Metastatic Non-small Cell Lung Cancers With Epidermal Growth Factor Receptor Mutations	NCT05299125	Metastatic Non-...	Amivantamab Lazertinib Pemetrexed 500 ...	18 Years -	Latin American Cooperative Oncology Group
Amivantamab, Lazertinib, and Pemetrexed for First-line Treatment of Recurrent/Metastatic Non-small Cell Lung Cancers With Epidermal Growth Factor Receptor Mutations	NCT05299125	Metastatic Non-...	Amivantamab Lazertinib Pemetrexed 500 ...	18 Years -	Latin American Cooperative Oncology Group

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