Neoplasms

All Conditions

Skin and Connective Tissue Diseases

Carcinoma

Carcinoma, Squamous Cell

Skin Neoplasms

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Neoplasms, Squamous Cell

Antineoplastic Agents

All Drugs and Chemicals

Amino Acids

Afatinib

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Tyrosine

Participants will receive afatinib 40 mg once a day. Each cycle is 4 weeks. They will have CT imaging (and/or digital photography) done at baseline and every 8 weeks while on treatment. Participants will have a baseline and on-treatment (at 4 weeks) tumor biopsy, and a biopsy at disease progression if feasible. Patients may remain on treatment as long as they are deriving clinical benefit, until disease progression or intolerable toxicity.

Participants will receive 40 mg Afatinib, once daily.

Afatinib 40 MG

Ashley Paneto-Matos

Zeynep Eroglu, MD

The primary purpose of this study is to find out if Afatinib can help treat participants with advanced cSCC.

Study of Afatinib in Advanced Cutaneous Squamous Cell Carcinoma

Phase 2 Study of Afatinib in Advanced Cutaneous Squamous Cell Carcinoma

Overall response rate (ORR) as defined by proportion of patients who have achieved a complete or partial response per RECIST 1.1 criteria

Progression free survival, defined as the time from first dose to the earlier date of assessment of progression or death by any cause in the absence of progression

Overall survival, as measured from the date of first dose to the date of death by any cause

Treatment-related adverse events per NCI CTCAE v5 criteria

Boehringer Ingelheim

H. Lee Moffitt Cancer Center and Research Institute

single oral dose of afatinib each day starting at a dose of 40 mg on day 1, continuously, until the development of progressive disease or unacceptable adverse events

Christoph Heining, Dr.

Whole-genome and transcriptome sequencing of patients with advanced solid tumors enrolled in the NCT/DKTK MASTER (Molecularly Aided Stratification for Tumor Eradication Research) program revealed recurrent NRG1 fusions in a substantial proportion of patients with KRAS wild-type (KRASwt) pancreatic adenocarcinoma (PDAC) and a case of signet-ring cell carcinoma of the appendix. NRG1 rearrangements drive tumor development through ERBB receptor-mediated signaling, as evidenced by objective response to ERBB inhibition in two cases of NRG1-rearranged PDAC in the MASTER cohort. Recently, NRG1 fusions have also been identified as a therapeutic target in a substantial number of the invasive mucinous subtype of lung adenocarcinoma (IMA) as well as in cholangiocellular carcinoma and, at low incidence, other tumor entities, suggesting oncogenic properties across a broader spectrum of malignancies.

Within this phase II clinical trial, the investigators aim to investigate the efficacy of the pan-ERBB inhibitor afatinib in advanced-stage NRG1-rearranged malignancies across all tumor entities following progression on standard therapy. Due to the enrichment of NRG1-rearrangements observed in KRASwt PDAC and IMA, two separate study arms will focus on these tumor entities while a third arm will allow inclusion of patients with any other NRG1 rearranged malignancy. Recruitment of adequate patient numbers in this well-defined molecular subgroup will be achieved by a multicenter approach including all DKTK partner sites and on-site pre-screening of PDAC for KRAS mutational status. Eligible patients will be identified by in-depth molecular characterization of tumors within the NCT/DKTK MASTER program or identification of a NRG1-rearranged tumor by another method for fusion detection (e.g. gene fusion panel).

Patients with NRG1-rearranged tumors fulfilling eligibility criteria will be offered to participate in the trial and receive afatinib monotherapy until tumor progression or discontinuation for other reasons. To assess mechanisms of secondary resistance and to investigate the clinical impact of liquid biopsies in this setting, blood samples for exome sequencing will be taken prior to initiation of the study treatment as well as at the time of progression.

Afatinib in Advanced NRG1-Rearranged Malignancies

Afatinib in Advanced NRG1-Rearranged Malignancies: the NCT/DKTK PMO-1604 Phase-II Trial

Primary objective of the study is to assess clinical activity of afatinib in adult patients with (locally) advanced or recurrent solid tumors harboring NRG1-rearrangments. Clinical efficacy is determined by disease control rate (DCR) including CR, PR, and SD according to RECIST v1.1 criteria.

To assess progression-free survival (PFS) of afatinib in adult patients with advanced solid tumors harboring NRG1-rearrangments.

To assess OS (overall survival) of afatinib in adult patients with advanced solid tumors harboring NRG1-rearrangments.

This endpoint includes all AEs, their severity, SAEs, the relation of AEs to the study treatment, dose modifications for toxicity and discontinuation of study treatment during the trial phase. Toxic effects are graded according to the National Cancer Institute Common Toxicity Criteria (CTCAE) version 5.0.

Patient Reported Outcomes including quality of life (QLQ) of patients treated with afatinib.

Patient-Reported Outcomes (PROs) including health-related quality of life (QoL) are calculated as the new European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 Summary Score recommended by the EORTC Quality of Life Group. In addition, the EORTC QLQ function and symptom scores will be calculated according to the actual EORTC Scoring Manual.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Study of Afatinib in Advanced Cutaneous Squamous Cell Carcinoma	NCT05070403	Squamous Cell C...	Afatinib 40 MG	18 Years -	H. Lee Moffitt Cancer Center and Research Institute
Afatinib in Advanced NRG1-Rearranged Malignancies	NCT04410653	Metastatic and ...	Afatinib 40 MG	18 Years -	German Cancer Research Center
Study of Afatinib in Advanced Cutaneous Squamous Cell Carcinoma	NCT05070403	Squamous Cell C...	Afatinib 40 MG	18 Years -	H. Lee Moffitt Cancer Center and Research Institute

Spots Global Cancer Trial Database for afatinib 40 mg