P2, N=239, Active, not recruiting, Janssen Research & Development, LLC | Trial completion date: Dec 2023 --> Dec 2024

Gong et al present two NCI-MATCH tumor-agnostic trials evaluating erdafitinib for FGFR-altered cancers, marking steppingstones in precision oncology.

P2, N=20, Active, not recruiting, Bai-Rong Xia | Recruiting --> Active, not recruiting

The literature in the field is not definite, and so far, there has been no consensus on the best approach in this situation. At present, as it is described in this editorial, the decision is applied on a case-by-case basis.

P1/2, N=83, Recruiting, Chinese PLA General Hospital | Trial primary completion date: Feb 2024 --> Jul 2024

To gain further insights into the conformational dynamics of Mundulone and the reference FGFR1 inhibitor, Lenvatinib, we conducted time-evolution analyses employing 200 ns molecular dynamics simulations (MDS) and essential dynamics...Overall, the findings indicate that Mundulone exhibits promising binding affinity, specific interactions, and favorable drug profiles, making it a promising lead candidate. Further experimental analysis will be necessary to confirm its effectiveness and safety profiles for therapeutic advancement in the cancer field.Communicated by Ramaswamy H. Sarma.

P3, N=629, Active, not recruiting, Janssen Research & Development, LLC | Trial completion date: Sep 2024 --> Nov 2026

P2, N=316, Active, not recruiting, Janssen Research & Development, LLC | Trial primary completion date: Aug 2022 --> Dec 2023

SUR combined with PDT can significantly enhance the inhibitory effect on CCA, and can be alleviated by two ferroptosis inhibitors (Ferrostatin-1, Deferoxamine). In conclusion, SUR combined with PDT exerted an anti-CCA effect by inducing ferroptosis. Combination therapy provides a new idea for the clinical treatment of CCA.

P2, N=30, Not yet recruiting, Tianjin Medical University Cancer Institute and Hospital

P2, N=160, Recruiting, Second Affiliated Hospital, School of Medicine, Zhejiang University | Not yet recruiting --> Recruiting | Initiation date: Jul 2023 --> Jan 2024

Erdafitinib did not meet its primary end point of efficacy as determined by ORR in treatment-refractory solid tumors harboring FGFR1-4 amplifications. Our findings support that rearrangements and gene mutations, but not amplifications, of FGFR remain the established FGFR alterations with approved indications for FGFR inhibition.

This study met its primary end point in patients with several pretreated solid tumor types harboring FGFR1-3 mutations or fusions. These findings support advancement of erdafitinib for patients with fibroblast growth factor receptor-altered tumors outside of currently approved indications in a potentially tumor-agnostic manner.

P2/3, N=482, Not yet recruiting, Hutchmed

P2, N=40, Not yet recruiting, Wuhan Union Hospital, China

P2, N=35, Active, not recruiting, National Cancer Institute (NCI)

P2, N=35, Completed, Janssen Research & Development, LLC | Active, not recruiting --> Completed | Trial completion date: Jun 2024 --> Mar 2024

P3, N=629, Active, not recruiting, Janssen Research & Development, LLC | Trial primary completion date: Feb 2024 --> Sep 2024

P=N/A, N=63, Not yet recruiting, Fudan University

No abstract available

The phase 3 THOR trial compared the efficacy of erdafitinib to chemotherapy or immunotherapy in FGFR3/2-altered advanced UC. THOR offers valuable data informing sequencing strategies, reinforcing the need for molecular testing in UC.

P2, N=35, Active, not recruiting, National Cancer Institute (NCI)

In this issue of Cancer Research, Hosni and colleagues discover a paracrine mechanism mediated by adipocyte precursor cells through which urothelial carcinomas become resistant to erdafitinib, a recently approved therapy inhibiting fibroblast growth factor receptors (FGFR)...The NRG1-mediated FGFR inhibitor resistance was amenable to intervention with pertuzumab, an antibody blocking the NRG1/HER3 axis...Because fibroblasts with the ASC/FAP signature are enriched in various carcinomas, it is possible that the paracrine signaling conferred by NRG1 is a pan-cancer mechanism of FGFR inhibitor resistance and tumor aggressiveness. See related article by Hosni et al., p. 725.

BALVERSA (erdafitinib), a selective pan-FGFR kinase inhibitor, has shown clinical activity against FGFR altered solid tumors in pts who exhausted standard treatment options... The large Chinese solid tumor cohort analysis showed comparable FGFR alts prevalence between Chinese and Western population. Differences in relationship between FGFR alts and PD-L1 expression across tumor types reflect the differential role of predominant FGFR types in each tumor type.

P2, N=108, Active, not recruiting, Janssen Research & Development, LLC | Trial completion date: Jul 2025 --> Mar 2025

FGFR1 drives chemoresistance and tumor aggressiveness, which FGFRi can reverse.

P1, N=36, Active, not recruiting, Oscotec Inc. | Recruiting --> Active, not recruiting

P1, N=14, Completed, Oscotec Inc. | Unknown status --> Completed | N=40 --> 14

P2, N=35, Recruiting, National Cancer Institute (NCI) | Initiation date: Jul 2024 --> Jan 2024

P2, N=78, Active, not recruiting, Hutchmed | Trial primary completion date: Sep 2023 --> Sep 2024

P2, N=316, Active, not recruiting, Janssen Research & Development, LLC | Trial primary completion date: Sep 2024 --> Oct 2023

P1, N=35, Active, not recruiting, Vanderbilt-Ingram Cancer Center | Trial completion date: Dec 2023 --> Sep 2024

P2, N=25, Recruiting, Qilu Hospital of Shandong University

P1/2, N=36, Active, not recruiting, Hutchison Medipharma Limited | Recruiting --> Active, not recruiting

P1/2, N=130, Completed, Hutchison Medipharma Limited | Active, not recruiting --> Completed

P1/2, N=13, Completed, Hutchmed | Active, not recruiting --> Completed

Downregulation of S100A11 plays a crucial role in enhancing the therapeutic response to Erdafitinib and reversing immunosuppressive tumor microenvironment.

Comparative analyses with FDA-approved FGFR inhibitors, erdafitinib and pemigatinib, revealed certain advantages of CPL304110 in both in vitro and in vivo assessments. Encouraging preclinical results led the way for the initiation of a Phase I clinical trial (01FGFR2018; NCT04149691) to further evaluate CPL304110 as a novel anticancer therapy.

P2, N=7, Terminated, University of Michigan | N=15 --> 7 | Suspended --> Terminated; Due to limited funding, trial was suspended, intending to restart with additional funds; then preliminary results were obtained, and research moved on to placebo controlled trial. Results for both have been published.

Combined erdafitinib and ICI resulted in high therapeutic efficacy. In aggregate, our work establishes that, in mice, co-alteration of FGFR3 and Trp53 results in high-grade, non-muscle-invasive UC and presents a previously underappreciated role for FGFR inhibition in blocking ICI-induced Treg expansion.

P2, N=34, Recruiting, Zhejiang Cancer Hospital

While both EPN patients did not respond to erdafitinib treatment, the FGFR1-ITD-harbouring tumour showed a significant decrease in tumour volume and contrast enhancement throughout treatment. The tumour remained stable 6 months after treatment discontinuation.