rilotumumab (AMG 102) / Amgen - LARVOL DELTA

Systematic Literature Review (SLR) of Randomized Controlled Trials (RCTs) of Treatments for First-Line (1L) Gastric Cancer/Gastroesophageal Junction Adenocarcinoma (GC/GEJ) in Adult Patients (ISPOR-EU 2024) - "Among trials of PD-1/PD-L1 inhibitors (tislelizumab, nivolumab, pembrolizumab, sugemalimab, sintilimab), improvements in overall survival (OS), progression-free survival (PFS), and objective response rate (ORR) were observed for PD-1/PD-L1 inhibitors plus chemotherapy versus chemotherapy alone at median follow-up times ranging from 11.6 to 54.3 months, with median OS, median PFS, and ORR ranging from 12.5 to 17.45 months, 6.9 to 10.94 months, and 47.3% to 68.6%, respectively...Among other targeted therapies, response and survival benefits compared to chemotherapy were mixed; improvements in response and survival were seen with the CLDN18.2 inhibitor zolbetuximab and the FGFR inhibitor bemarituzumab, while benefits compared to chemotherapy were not seen with cetuximab, ramucirumab, andecaliximab, onartuzumab, rilotumumab, pazopanib, or ipatasertib... PD-1/PD-L1 inhibitors showed improved efficacy compared to chemotherapy for the treatment of 1L GC/GEJ; while other..."

Clinical • IO biomarker • Review • Esophageal Cancer • Gastric Cancer • Gastroesophageal Cancer • Gastroesophageal Junction Adenocarcinoma • Oncology • Solid Tumor • CLDN18 • CTLA4 • HER-2

A phase 3, multicenter, randomized, double-blind, placebo-controlled study of rilotumumab in combination with cisplatin and capecitabine (CX) as first-line therapy for Asian patients (pts) with advanced MET-positive gastric or gastroesophageal junction... (ASCO-GI 2015) - Abstract #TPS226; P3, N=450; Sponsor: Amgen; NCT02137343; “The primary endpoints are PFS and OS. A log-rank test stratified by the randomization factors will compare PFS and OS between arms. Key secondary endpoints include 12-month survival rate, time to progression, objective response and disease control rates, duration of/time to response, safety, and PK.”

Trial status • Oncology

QUILT-2.013: First-Line Treatment for Extensive Stage Small Cell Lung Cancer (clinicaltrials.gov) - P1/2 | N=213 | Terminated | Sponsor: NantCell, Inc. | Phase classification: P1b/2 ➔ P1/2 | Completed ➔ Terminated; Subjects discontinued study

Combination therapy • Phase classification • Trial termination • Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor

Panitumumab Combination Study With Rilotumumab or Ganitumab in Wild-type Kirsten Rat Sarcoma Virus Oncogene Homolog (KRAS) Metastatic Colorectal Cancer (mCRC) (clinicaltrials.gov) - P1/2 | N=177 | Completed | Sponsor: NantBioScience, Inc. | Phase classification: P1b/2 ➔ P1/2

Combination therapy • Metastases • Phase classification • Colon Cancer • Colorectal Adenocarcinoma • Colorectal Cancer • Gastrointestinal Cancer • Gastrointestinal Disorder • Oncology • Sarcoma • Solid Tumor • KRAS

First comprehensive report of impact of genomic alterations, chemotherapy, targeted therapy and immunotherapy on outcomes in the genomics driven squamous master protocol LungMAP. (ASCO 2018) - P2/3; "...Completed studies evaluated taselisib (T) for PI3K mutations, palbociclib(P) for cell cycle gene alterations (CCGA), AZD4547(A) for FGFR alterations, rilotumumab and erlotinib(RE) for c-MET positive tumors, and durvalumab(Dur) . Originally including randomization to docetaxel(Doc), the studies were amended to single-arm phase 2... As of January 5, 2018, 1407 patients registered to screening, 1244 with biomarker results and 529 patients have registered to a sub-study. Fifty-six eligible patients registered to Doc, 66 to Dur, and 90 to a targeted therapy arm (25 to A, 31 to P, 26 to T, 5 to E, 3 to RE). Relative to the Doc (median = 7.6 months(m)), overall survival was better for Dur (HR [95%CI]: 0.63 [0.42-0.96], median = 11.6 m)."

Clinical • IO biomarker • PD(L)-1 Biomarker • Non Small Cell Lung Cancer

Rilotumumab Resistance Acquired by Intracrine Hepatocyte Growth Factor Signaling. (PubMed, Cancers (Basel)) - "Although resistant cells were significantly more malignant, they retained sensitivity to Met kinase inhibition and acquired sensitivity to inhibition of ER stress signaling and cholesterol biosynthesis. Defining this mechanism reveals details of a rapidly acquired yet highly-orchestrated multisystem route of resistance to a selective molecularly-targeted agent and suggests strategies for early detection and effective intervention."

Journal • Brain Cancer • CNS Tumor • Glioblastoma • Oncology • Solid Tumor • HGF • MET

Computational Drug Discovery in Ankylosing Spondylitis-induced Osteoporosis Based on Data Mining and bioinformatics analysis. (PubMed, World Neurosurg) - "In conclusion, CARLUMAB, BERMEKIMAB, RILONACEPT, RILOTUMUMAB and FICLATUZUMAB were first identified as the potential drugs for the treatment of AS-OP, proving the value of text mining and pathway analysis in drug discovery."

Journal • Ankylosing Spondylitis • Immunology • Inflammatory Arthritis • Orthopedics • Osteoporosis • Rheumatology • Seronegative Spondyloarthropathies

Application of Approved Cisplatin Derivatives in Combination Therapy against Different Cancer Diseases. (PubMed, Molecules) - "The aim of current study is the comparison of therapeutic combinations of the currently applied in clinical practice: Cisplatin, Carboplatin, Oxaliplatin, Nedaplatin, Lobaplatin, Heptaplatin, and Satraplatin...The very important strategy for the improvement of the antitumor effect against different cancers is synergistic combination of Cisplatin derivatives with: (1) anticancer agents-Fluorouracil, Gemcitabine, Cytarabine, Fludarabine, Pemetrexed, Ifosfamide, Irinotecan, Topotecan, Etoposide, Amrubicin, Doxorubicin, Epirubicin, Vinorelbine, Docetaxel, Paclitaxel, Nab-Paclitaxel; (2) modulators of resistant mechanisms; (3) signaling protein inhibitors-Erlotinib; Bortezomib; Everolimus; (4) and immunotherapeutic drugs-Atezolizumab, Avelumab, Bevacizumab, Cemiplimab, Cetuximab, Durvalumab, Erlotinib, Imatinib, Necitumumab, Nimotuzumab, Nivolumab, Onartuzumab, Panitumumab, Pembrolizumab, Rilotumumab, Trastuzumab, Tremelimumab, and Sintilimab. An important approach for..."

Combination therapy • IO biomarker • Journal • Review • Oncology

Lung-MAP: Biomarker-Targeted Second-Line Therapy in Treating Patients With Recurrent Stage IV Squamous Cell Lung Cancer (clinicaltrials.gov) - P=N/A | N=1864 | Completed | Sponsor: Southwest Oncology Group | Active, not recruiting ➔ Completed

Biomarker • Trial completion • Cervical Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • EGFR • EML4 • TP63

Comparative efficacy and safety of anti-HGF/MET pathway agents plus chemotherapy versus chemotherapy alone as first-line treatment in advanced gastric cancer: a protocol for a systematic review and meta-analysis. (PubMed, BMJ Open) - "Randomised controlled trials (RCTs) were undertaken assessing whether the addition of anti-HGF/MET agent (rilotumumab or onartuzumab) to chemotherapy improves survival outcomes of advanced GC, but conflict conclusions were reached...It is anticipated that the dissemination of results will take place at conferences and through publication in a peer-review journal, any adjustments from the protocol will be clearly documented and explained in its final report. CRD42020177404."

Journal • Retrospective data • Review • Gastric Cancer • Gastrointestinal Cancer • Gastrointestinal Disorder • Oncology • Solid Tumor • HGF

Targeting HGF/c-Met Axis Decreases Circulating Regulatory T Cells Accumulation in Gastric Cancer Patients. (PubMed, Cancers (Basel)) - "In the MEGA-ACCORD20-PRODIGE17 trial, GC patients received an anti-HGF antibody treatment (rilotumumab), which had been described to have an anti-angiogenic activity by decreasing proliferation of endothelial cells and tube formation...Thus, we identified that HGF indirectly triggers Treg accumulation via c-Met-expressing monocytes in the peripheral blood of GC patients. Our study provides arguments for potential alternative use of HGF/c-Met targeted therapies based on their immunomodulatory properties which could lead to the development of new therapeutic associations in cancer patients, for example with immune checkpoint inhibitors."

Clinical • IO biomarker • Journal • Gastric Cancer • Gastrointestinal Cancer • Hepatology • Immune Modulation • Inflammation • Oncology • Solid Tumor • IL10 • MET

First comprehensive report of impact of genomic alterations, chemotherapy, targeted therapy and immunotherapy on outcomes in the genomics driven squamous master protocol LungMAP. (ASCO 2018) - P2/3; "...Completed studies evaluated taselisib (T) for PI3K mutations, palbociclib(P) for cell cycle gene alterations (CCGA), AZD4547(A) for FGFR alterations, rilotumumab and erlotinib(RE) for c-MET positive tumors, and durvalumab(Dur) . Originally including randomization to docetaxel(Doc), the studies were amended to single-arm phase 2... As of January 5, 2018, 1407 patients registered to screening, 1244 with biomarker results and 529 patients have registered to a sub-study. Fifty-six eligible patients registered to Doc, 66 to Dur, and 90 to a targeted therapy arm (25 to A, 31 to P, 26 to T, 5 to E, 3 to RE). Relative to the Doc (median = 7.6 months(m)), overall survival was better for Dur (HR [95%CI]: 0.63 [0.42-0.96], median = 11.6 m)."

Clinical • IO biomarker • PD(L)-1 Biomarker • Non Small Cell Lung Cancer

Second-Line, Biomarker-Driven Therapies for Squamous NSCLC: Report on Lung-MAP SWOG S1400 (IASLC.org) - "The primary objective of this study was to establish an infrastructure that could be used to efficiently evaluate targeted therapies in biomarker subgroups. The infrastructure created allowed for biomarker testing and evaluation of targeted therapies with regulatory intent. Patients included in this trial had stage IV or recurrent squamous cell lung cancer and had received previous platinum-doublet chemotherapy."

Biomarker • Online posting

Biomarker-driven therapies for previously treated squamous non-small-cell lung cancer (Lung-MAP SWOG S1400): a biomarker-driven master protocol. (PubMed, Lancet Oncol) - P2/3 | "Lung-MAP (S1400) met its goal to quickly address biomarker-driven therapy questions in squamous non-small-cell lung cancer. In early 2019, a new screening protocol was implemented expanding to all histological types of non-small-cell lung cancer and to add focus on immunotherapy combinations for anti-PD-1 and anti-PD-L1 therapy-relapsed disease. With these changes, Lung-MAP continues to meet its goal to focus on unmet needs in the treatment of advanced lung cancers."

Biomarker • Clinical • IO biomarker • Journal • Lung Cancer • Lung Non-Small Cell Squamous Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • FGFR • HRD • PIK3CA

Lung-MAP: Biomarker-Targeted Second-Line Therapy in Treating Patients With Recurrent Stage IV Squamous Cell Lung Cancer (clinicaltrials.gov) - P=N/A; N=1864; Active, not recruiting; Sponsor: Southwest Oncology Group; Phase classification: P2/3 ➔ P=N/A; N=10000 ➔ 1864

Biomarker • Clinical • Enrollment change • Phase classification • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Combination of HGF/MET-targeting agents and other therapeutic strategies in cancer. (PubMed, Crit Rev Oncol Hematol) - "Agents targeting MET and its ligand hepatocyte growth factor (HGF) including small molecules such as crizotinib, tivantinib and cabozantinib or antibodies including rilotumumab and onartuzumab have proven their values in different tumors. Recently, capmatinib was approved for treatment of metastatic lung cancer with MET exon 14 skipping...Preclinical and clinical studies on the combination of HGF/MET-targeted agents with conventional chemotherapeutics or molecularly targeted treatments (EGFR, VEGFR, HER2, RAF/MEK, and PI3K/Akt targeting agents) and also the value of biomarkers are examined. Our deeper understanding of molecular mechanisms underlying successful pharmacological combinations is crucial to find the best personalized treatment regimens for cancer patients."

Journal • Review • Lung Cancer • Oncology • Solid Tumor • EGFR • HER-2

MEGA (Met or EGFR Inhibition in Gastroesophageal Adenocarcinoma): FOLFOX Alone or in Combination With AMG 102 or Panitumumab as First-line Treatment in Patients With Advanced Gastroesophageal Adenocarcinoma (clinicaltrials.gov) - P2; N=162; Completed; Sponsor: UNICANCER; Active, not recruiting ➔ Completed

Clinical • Combination therapy • Trial completion • Esophageal Adenocarcinoma • Esophageal Cancer • Gastric Adenocarcinoma • Gastric Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • MET

Paracrine HGF promotes EMT and mediates the effects of PSC on chemoresistance by activating c-Met/PI3K/Akt signaling in pancreatic cancer in vitro. (PubMed, Life Sci) - "PSCs can activate the c-Met/PI3K/Akt pathway in PCCs via paracrine HGF, induce EMT of PCCs and inhibit cancer cell apoptosis, thus enhance chemoresistance to Gem in PCCs."

Journal • Preclinical • Gastrointestinal Cancer • Hepatology • Oncology • Pancreatic Cancer • Solid Tumor • CDH1 • MET • VIM

Rilotumumab in treating patients with persistent or recurrent ovarian epithelial cancer, fallopian tube cancer, or primary peritoneal cancer (clinicaltrials.gov) - P2, N=50; Recruiting -> Active, not recruiting.

Enrollment closed • Oncology • Ovarian Cancer

Rilotumumab in Treating Patients With Persistent or Recurrent Ovarian Epithelial Cancer, Fallopian Tube Cancer, or Primary Peritoneal Cancer (clinicaltrials.gov) - P2; N=31; Completed; Sponsor: Gynecologic Oncology Group; Active, not recruiting ➔ Completed; N=50 ➔ 31; Trial primary completion date: Jan 2100 ➔ Jul 2012

Enrollment change • Trial completion • Trial primary completion date • Biosimilar • Endometrial Cancer • Oncology • Ovarian Cancer • Reperfusion Injury

Mechanistically detailed systems biology modeling of the HGF/Met pathway in hepatocellular carcinoma. (PubMed, NPJ Syst Biol Appl) - "Furthermore, the model predicted patient-specific synergy and antagonism of efficacy and potency for combination of AXT050 with sorafenib, cabozantinib, and rilotumumab. Overall, the model provides a valuable framework for studying the efficacy of drugs targeting receptor tyrosine kinase interaction with integrins, and identification of synergistic drug combinations for the patients."

Journal • Gastrointestinal Cancer • Hepatocellular Cancer • Oncology • Solid Tumor

Biomarker-Targeted Second-Line Therapy in Treating Patients With Recurrent Stage IIIB-IV Non-Small Cell Lung Cancer (clinicaltrials.gov) - P2/3; N=10000; Not yet recruiting; Sponsor: Southwest Oncology Group

New P2/3 trial • Biosimilar • Non Small Cell Lung Cancer • Oncology • Renal Cell Carcinoma

Lung-MAP (S1400) Lung Cancer Master Protocol: Accrual, demographics, and molecular markers (ASCO 2016) - P2/3, N=735; Lung-MAP (NCT02154490); "This novel master protocol designed to challenge current drug development paradigms and expedite drug registration, is demonstrating feasibility of genomic screening and confirms anticipated prevalence of targeted alterations in SCCA."

Biomarker • P2/3 data • Oncology

Lung-MAP: S1400 Biomarker-Targeted Second-Line Therapy in Treating Patients With Recurrent Stage IIIB-IV Non-Small Cell Lung Cancer (clinicaltrials.gov) - P2/3; N=10000; Recruiting; Sponsor: Southwest Oncology Group; Not yet recruiting -> Recruiting

Enrollment open • Biosimilar • Non Small Cell Lung Cancer • Oncology

Lung cancer “master protocol” eyed as paradigm-changing approach to drug development (Pink Sheet - Informa) - "The biomarker-driven, multi-arm, multi-drug [P2/3] registration trial is expected to get under way in March 2014...four companies are supplying targeted therapies: Amgen Inc. [Rilotumumab], AstraZeneca PLC [AZD4547], Genentech Inc. [PI3 kinase inhibitor] and Pfizer Inc [Palbociclib]. AstraZeneca’s MedImmune division is providing a PD-L1 inhibitor [MEDI4736]"

Anticipated new P2/3 trial • Non Small Cell Lung Cancer • Oncology