lucitanib (E 3810) / Clovis, HaiHe Biopharma, Servier - LARVOL DELTA

Efficacy and safety of lucitanib (AL3810) in second or subsequent-line treatment of advanced recurrent or metastatic thymic carcinoma: A randomized, double-blind, placebo-controlled multicenter phase II trial (ESMO Asia 2024) - "No grade 4/5 TRAEs were observed. Conclusions This study suggests that Lucitanib may have significant clinical benefit and has acceptable safety for patients with advanced recurrent or metastatic thymic carcinoma."

Clinical • Metastases • P2 data • Oncology • Solid Tumor • Thymic Carcinoma • Thymus Cancer • FGFR1 • FLT1 • PDGFRA

The anti-angiogenic multi-kinase inhibitor AL3810 exerts differential effects on tumor infiltrating CD8+ T cell subsets and cooperatively enhances the anti-tumor effects of PD-1 blockade therapy (EORTC-NCI-AACR 2024) - "Anti-angiogenic inhibitor AL3810 can sustain Tpex and reduce Tex subpopulation in tumor, and enhance the expression of immune co-stimulatory receptors and the production of IFN-γ and TNF-α in all four CD8+ T subsets, which might facilitate the reinvigoration of CD8+ T cells by ICI. PD-1 blockade might activate Tpex and stimulate their differentiation into functional CD8+ T cells, and therefore exerts synergistic anti-tumor efficacy."

IO biomarker • Oncology • Solid Tumor • CD8 • FGFR • GZMB • HAVCR2 • ICOS • IFNG • TNFA

A randomized , double-blind , placebo-controlled , multicenter Phase II clinical study to evaluate the efficacy and safety of Lucitanib (AL3810) in patients with advanced recurrent or metastatic thymic carcinoma who have failed at least one line of chemotherapy... (Haihe Biopharma Press Release) - P2 | N=60 | AL3810-202 (CTR20180996) | "Investigator-assessed median PFS was 6.6 months in Lucitanib group and 1.9 months in control group (p=0.0306, HR =0.53). The risk of disease progression or death was reduced by 47%. IRC assessed median PFS was 5.8 months in Lucitanib group and 3.7 months in control group (p=0.1050, HR=0.60). The risk of disease progression or death was reduced by 40%. The results of each subgroup analysis (based on forest plots) were consistent, indicating that the Lucitanib group had PFS benefits."

P2 data • Thymic Carcinoma

Efficacy and Safety of Delitinib (AL3810) in Second- or Post-Line Treatment of Advanced Recurrent or Metastatic Thymic Carcinoma: A Randomized, Double-blind, Placebo-Controlled, Multicenter Phase II Clinical Study (CSCO 2024) - "Study Group: [Organizing Committee]"

Clinical • Metastases • P2 data • Oncology • Solid Tumor • Thymic Carcinoma • Thymus Cancer

An open-lable phase Ib/II study, Lucitanib combined with Toripalimab in the treatment of advanced recurrent or metastatic solid tumors (ChiCTR) - P1/2 | N=180 | Completed | Sponsor: Sun Yat-sen University Cancer Center; Haihe Biopharma Co.,Ltd.

Metastases • New P1/2 trial • Esophageal Cancer • Gastric Cancer • Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor

Fibroblast growth factor receptor signaling in estrogen receptor-positive breast cancer: mechanisms and role in endocrine resistance. (PubMed, Front Oncol) - "Current clinical trials, including those evaluating FGFR inhibitors like erdafitinib, lucitanib, and dovitinib, have demonstrated mixed outcomes, underscoring the complexity of FGFR signaling in breast cancer. In conclusion, targeting FGFR signaling in ER+ breast cancer presents both challenges and opportunities. A deeper understanding of the molecular mechanisms and resistance pathways is crucial for the successful integration of FGFR inhibitors into clinical practice, aiming to improve outcomes for patients with endocrine-resistant breast cancer."

Journal • Review • Breast Cancer • Endocrine Cancer • Estrogen Receptor Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • EIF4EBP1 • ER • FGFR • FGFR1 • FGFR2 • FGFR3 • FGFR4 • NSD3

Targeting angiogenesis for improved survival in mantle cell lymphoma (AACR 2024) - "Lucitanib treatment significantly prolonged median overall survival significantly in the systemic MCL model. Our data demonstrates that targeting angiogenesis in MCL can provide therapeutic benefits, as demonstrated in preclinical MCL models."

Hematological Malignancies • Lymphoma • Mantle Cell Lymphoma • Oncology • B2M • CCND1 • FLT1 • PDGFA • SOX11

A Study to Evaluate Rucaparib in Combination With Other Anticancer Agents in Participants With a Solid Tumor (SEASTAR) (clinicaltrials.gov) - P1/2 | N=25 | Terminated | Sponsor: pharmaand GmbH | Phase classification: P1b/2 ➔ P1/2

Combination therapy • Phase classification • Breast Cancer • Oncology • Ovarian Cancer • Solid Tumor • Triple Negative Breast Cancer • Urothelial Cancer • BRCA1 • BRCA2 • RAD51C • RAD51D

LIO-1: Initial phase 2 experience of lucitanib + nivolumab in patients with metastatic or recurrent cervical cancer (NCT04042116; ENGOT-GYN3/AGO/LIO) (SGO 2022) - P1b/2 | No abstract available

Clinical • P2 data • Cervical Cancer • Oncology • Solid Tumor

Phase 2 Results From the LIO-1 STUDY (NCT04042116; ENGOT-GYN3/AGO/LIO): Efficacy and Safety of Lucitanib + Nivolumab in Patients With Advanced Gynaecological Malignancies (ESGO 2022) - P1b/2 | "Patients with EC, CC or EOCC received ≥1 prior platinum-based chemotherapies (CC, ± bevacizumab; EOCC, + taxane); patients with OC received ≥2 prior chemotherapies (including ≥1 platinum doublet). Lucitanib + nivolumab displays anti-tumour activity in patients with advanced gynaecological malignancies, including clear-cell cancer. Effective dose titration resulted in manageable safety, similar to previous reports."

Clinical • P2 data • Cardiovascular • Cervical Cancer • Endometrial Cancer • Gynecologic Cancers • Hypertension • Oncology • Ovarian Cancer • Solid Tumor

ENGOT-GYN3: A Study to Evaluate Lucitanib in Combination With Nivolumab in Patients With a Solid Tumor (clinicaltrials.gov) - P1b/2 | N=227 | Suspended | Sponsor: Clovis Oncology, Inc. | Active, not recruiting ➔ Suspended

Combination therapy • Metastases • Trial suspension • Endometrial Cancer • Gynecologic Cancers • Oncology • Solid Tumor

Efficacy and safety of lucitanib + nivolumab in patients with advanced gynecologic malignancies: Phase 2 results from the LIO-1 study (NCT04042116; ENGOT-GYN3/AGO/LIO). (ASCO 2022) - P1b/2 | " Patients (pts) with advanced, recurrent, or metastatic endometrial cancer (EC, who received ≥1 prior platinum-based chemotherapy); cervical cancer (CC, who received ≥1 prior platinum-based chemotherapy ± bevacizumab); high-grade ovarian cancer (OC, who received ≥2 prior chemotherapies); or EC/OC with clear-cell histology (EOCC, who received ≥1 prior platinum-based chemotherapy + taxane) were enrolled. The combination of lucitanib + nivolumab is active in the treatment of advanced gynecological malignancies and has a manageable safety profile through effective dose titration. Stage 2 enrollment has continued in the CC cohort. Biomarker analysis is ongoing, and more mature efficacy and safety data will be presented at the meeting."

Clinical • IO biomarker • P2 data • Cervical Cancer • Endometrial Cancer • Gynecologic Cancers • Hypertension • Oncology • Ovarian Cancer

A phase Ib study of oral administration of lucitanib in combination with fulvestrant in patients with HR+ metastatic breast cancer (mBC) (SABCS 2017) - "The combination is feasible but requires close patient monitoring and intensive management of adverse events. Those are in line with the anti-angiogenic activity of lucitanib."

Biomarker • Clinical • Combination therapy • P1 data • Hormone Receptor Breast Cancer

Gene signature and connectivity mapping to assist with drug prediction for pancreatic ductal adenocarcinoma. (PubMed, Surg Oncol) - "Using available genetic atlas data, potential drug candidates for treatment of PDAC were identified based on differentially expressed genes, protein interaction analysis and connectivity mapping. These results may help focus efforts on identifying targeted agents with potential therapeutic efficacy for evaluation in prospective clinical trials of patients with PDAC."

Journal • Gastrointestinal Cancer • Hepatology • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • AURKA • CCNB2 • CDC20 • COL1A1 • COL1A2 • COL3A1 • CTRC • ITGB1 • KRAS • PRSS3 • REG1A • SDC1

A Study to Evaluate Rucaparib in Combination With Other Anticancer Agents in Patients With a Solid Tumor (SEASTAR) (clinicaltrials.gov) - P1b/2 | N=25 | Terminated | Sponsor: Clovis Oncology, Inc. | N=329 ➔ 25 | Trial completion date: Mar 2024 ➔ Apr 2022 | Active, not recruiting ➔ Terminated | Trial primary completion date: Oct 2023 ➔ Mar 2022; Due to a change in development priorities, no further clinical development of the lucitanib plus rucaparib or lucitanib plus sacituzumab govitecan combinations is planned at this time.

Combination therapy • Enrollment change • Trial completion date • Trial primary completion date • Trial termination • Breast Cancer • Oncology • Ovarian Cancer • Solid Tumor • Triple Negative Breast Cancer • Urothelial Cancer • BRCA1 • BRCA2 • RAD51C • RAD51D

Lucitanib With Nivolumab Sees Responses in Gynecological Cancer Treatment (AJMC) - "The LIO-1 study (NCT04042116) is examining the combination of lucitanib with the PD-1 inhibitor nivolumab across a range of solid tumor cancers. During the 2022 annual meeting of the American Society of Clinical Oncology, Manish R. Patel, MD...presented findings from the phase 1/2 dose escalation study evaluating lucitanib with nivolumab in advanced gynecological cancers, including cervical cancer (CC), endometrial cancer (EC), and ovarian cancer (OC)."

Media quote

Population Pharmacokinetic Modeling of Lucitanib in Patients with Advanced Cancer. (PubMed, Eur J Drug Metab Pharmacokinet) - P1/2, P2 | "The PopPK model adequately described lucitanib pharmacokinetics. High between-subject pharmacokinetic variability supports a safety-based dose-titration strategy currently being used in an ongoing clinical study of lucitanib to optimize drug exposure and clinical benefit."

Journal • PK/PD data • Hepatology • Oncology • Renal Disease • CYP2C8 • FGFR

The Multi-Kinase Inhibitor Lucitanib Enhances the Antitumor Activity of Coinhibitory and Costimulatory Immune Pathway Modulators in Syngeneic Models. (PubMed, J Immunother) - "These data indicate that lucitanib can modulate vascular and immune components of the tumor microenvironment and cooperate with immunotherapy to enhance antitumor efficacy. They support the clinical development of lucitanib combined with immune pathway modulators to treat cancer."

IO biomarker • Journal • Colon Cancer • Gastrointestinal Cancer • Immune Modulation • Inflammation • Oncology • CD31 • CD4 • CD8 • CTLA4 • ICOS • PECAM1

"Would these be the good sign for $CLVS 🤔 #ASCO22 FAP-2286 https://t.co/n3jCp1qnua Lucitanib https://t.co/zAP5KRBw5O" (@iffbdgd)

Clovis Oncology Highlights Rubraca (Rucaparib) and FAP-2286 Data to be Presented at 2022 ASCO Annual Meeting (Businesswire) - "Clovis Oncology, Inc...announced today that seven abstracts from the company’s pipeline, including late-breaking data from the ATHENA-MONO Phase 3 clinical trial evaluating Rubraca monotherapy versus placebo and imaging of solid tumors using FAP-2286, will be presented in oral and poster sessions during the 2022 American Society of Clinical Oncology (ASCO) Annual Meeting held June 3-7, 2022, in Chicago. Three additional retrospective analyses evaluating Rubraca and PARP inhibitors will be published online during the meeting."

Clinical data • Gynecologic Cancers • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Solid Tumor

A Phase Ib Study of Lucitanib (AL3810) in a Cohort of Patients with Recurrent and Metastatic Nasopharyngeal Carcinoma. (PubMed, Oncologist) - P1 | "Lucitanib has promising clinical activity and tolerable safety profile in heavily pretreated patients with NPC. Patients who responded to lucitanib treatment generally achieved a long DoR. Lucitanib is now being evaluated in phase II/III studies."

Journal • P1 data • Nasopharyngeal Carcinoma • Oncology • Solid Tumor • FLT1

ENGOT-GYN3: A Study to Evaluate Lucitanib in Combination With Nivolumab in Patients With a Solid Tumor (clinicaltrials.gov) - P1b/2; N=227; Active, not recruiting; Sponsor: Clovis Oncology, Inc.; Recruiting ➔ Active, not recruiting

Clinical • Combination therapy • Enrollment closed • Endometrial Cancer • Gynecologic Cancers • Oncology • Solid Tumor

[VIRTUAL] A phase-Ib study of lucitanib (AL3810) in a cohort of patients with recurrent and metastatic nasopharyngeal carcinoma (NPC) (ESMO Asia 2020) - P1 | "Funding: Shanghai HaiHe Pharmaceutical Co., Ltd. Clinical trial identification: NCT03260179."

Clinical • P1 data • Hypertension • Nasopharyngeal Carcinoma • Oncology • Renal Disease • Solid Tumor • FGFR1 • FLT1 • PDGFRA

[VIRTUAL] Initial clinical experience of lucitanib + nivolumab in advanced metastatic solid tumours: Data from the phase Ib/II LIO-1 study (CO-3810-101; NCT04042116) (ESMO 2020) - P1b/2 | "Funding: Clovis Oncology, Inc. Clinical trial identification: NCT04042116."

Clinical • IO Biomarker • P1/2 data • Anal Carcinoma • Cervical Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • MSI • PD-L1 • TMB

[VIRTUAL] LIO-1: A phase II study of lucitanib + nivolumab in patients (pts) with gynaecological tumours (CO-3810-101; NCT04042116; ENGOT-GYN3/AGO/LIO) (ESMO 2020) - P1b/2 | "Funding: Clovis Oncology, Inc. Clinical trial identification: NCT04042116."

Clinical • IO Biomarker • P2 data • Gynecologic Cancers • Oncology • Ovarian Cancer • FGFR1 • FLT1 • MSI • PD-L1 • TMB