lexatumumab (ETR2-ST01) / GSK - LARVOL DELTA

Celastrol enhances TRAIL‑R2‑mediated apoptosis and cytotoxicity in human renal cell carcinoma cells in caspase‑dependent manner. (PubMed, Oncol Rep) - "Furthermore, the cytotoxicity induced by that combination was significantly suppressed by the DR5:Fc chimeric protein, as well as specific inhibitors of caspase‑8, ‑9, ‑6 and ‑3. Taken together, these results indicated that celastrol enhances both TRAIL‑R2‑mediated apoptosis and cytotoxicity by upregulating TRAIL‑R2 and activating the caspase cascade, indicating the possibility of using it in combination with lexatumumab as an innovative therapeutic strategy for treating RCC."

Journal • Genito-urinary Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • CASP8 • CASP9 • TNFA

TRAIL-mediated signaling in bladder cancer: realization of clinical efficacy of TRAIL-based therapeutics in medical oncology. (PubMed, Med Oncol) - "Certain clues of scientific evidence have provided encouraging results about efficacy of these agonistic antibodies (lexatumumab and mapatumumab) against bladder cancer cell lines. Therefore, multipronged approaches consisting of natural products, chemotherapeutics, and agonistic antibodies will realistically and mechanistically provide proof-of-concept for the translational potential of these combinatorial strategies in well-designed clinical trials."

Journal • Review • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor • Urothelial Cancer

A first-in-human phase Ia/b, open-label, multicenter study of the TRAILR2 agonist BI 905711 in patients (pts) with advanced gastrointestinal (GI) cancers. (ASCO-GI 2022) - P1 | "In preclinical assays, BI 905711 demonstrated a potency shift of ̃1000 fold versus the 1st-generation TRAILR2 agonist lexatumumab. Secondary endpoints include PK parameters and OR in pts with measurable disease (phase Ia), and disease control, tumor shrinkage, duration of response, and progression-free survival (phase Ib). Trial enrollment is ongoing, with 33 pts enrolled to date."

Clinical • P1 data • Biliary Cancer • Cholangiocarcinoma • Colorectal Cancer • Gallbladder Cancer • Gastrointestinal Cancer • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Small Intestinal Carcinoma • TNFRSF10B

miR-3132 upregulates surface TRAIL to induce apoptotic cell death in cancer cells. (PubMed, Am J Cancer Res) - "This selective antitumor potential of the TRAIL pathway has been harnessed by development of therapeutics including recombinant (rh)TRAIL and TRAIL-receptor agonist antibodies such as mapatumumab and lexatumumab. Our data further suggests that the binding of miR-3132 to toll-like receptors could be the upstream pathway for the interferon response. The current study the first report to demonstrate miR-3132's in vitro efficacy and preliminary mechanism of action in cancer cell lines."

Journal • Colon Cancer • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor

Testing the Addition of the Pill Chemotherapy, Cabozantinib, to the Standard Immune Therapy Nivolumab Compared to Standard Chemotherapy for Non-small Cell Lung Cancer (clinicaltrials.gov) - P2; N=142; Recruiting; Sponsor: National Cancer Institute (NCI); Not yet recruiting ➔ Recruiting

Clinical • Enrollment open • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Thoracic Cancer • ALK • PD-L1 • RET • ROS1

Testing the Addition of the Pill Chemotherapy, Cabozantinib, to the Standard Immune Therapy Nivolumab Compared to Standard Chemotherapy for Non-small Cell Lung Cancer (clinicaltrials.gov) - P2; N=142; Not yet recruiting; Sponsor: National Cancer Institute (NCI)

Clinical • New P2 trial • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Thoracic Cancer • ALK • PD-L1 • RET • ROS1

Ramucirumab and Trifluridine/Tipiracil or Paclitaxel for the Treatment of Patients With Previously Treated Advanced Gastric or Gastroesophageal Junction Cancer (clinicaltrials.gov) - P2; N=116; Not yet recruiting; Sponsor: Academic and Community Cancer Research United; Initiation date: Mar 2021 ➔ Jun 2021

Clinical • Head-to-Head • Trial initiation date • Esophageal Cancer • Gastric Adenocarcinoma • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • Oncology • Solid Tumor • HER-2

Ramucirumab and Pembrolizumab for the Treatment of EGFR Mutant Recurrent or Metastatic Non-small Cell Lung Cancer (clinicaltrials.gov) - P2; N=34; Recruiting; Sponsor: Ohio State University Comprehensive Cancer Center; Not yet recruiting ➔ Recruiting

Clinical • Enrollment open • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • PD-L1

Ramucirumab in Treating Patients With Advanced or Metastatic, Previously Treated Biliary Cancers That Cannot Be Removed by Surgery (clinicaltrials.gov) - P2; N=61; Active, not recruiting; Sponsor: M.D. Anderson Cancer Center; Recruiting ➔ Active, not recruiting; Trial primary completion date: Dec 2020 ➔ Dec 2021

Clinical • Enrollment closed • Trial primary completion date • Biliary Cancer • Cholangiocarcinoma • Gallbladder Cancer • Gastrointestinal Cancer • Hepatology • Liver Cancer • Oncology • Solid Tumor • FGFR

Ramucirumab and Trifluridine/Tipiracil or Paclitaxel for the Treatment of Patients With Previously Treated Advanced Gastric or Gastroesophageal Junction Cancer (clinicaltrials.gov) - P2; N=116; Not yet recruiting; Sponsor: Academic and Community Cancer Research United; Initiation date: Dec 2020 ➔ Mar 2021

Clinical • Head-to-Head • Trial initiation date • Esophageal Cancer • Gastric Adenocarcinoma • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • Oncology • Solid Tumor • HER-2

Ramucirumab and Trifluridine/Tipiracil or Paclitaxel for the Treatment of Patients With Previously Treated Advanced Gastric or Gastroesophageal Junction Cancer (clinicaltrials.gov) - P2; N=116; Not yet recruiting; Sponsor: Academic and Community Cancer Research United

Clinical • Head-to-Head • New P2 trial • Esophageal Cancer • Gastric Adenocarcinoma • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • Oncology • Solid Tumor • HER-2

Testing of TAK228 (MLN0128, Sapanisertib) Plus Docetaxel to the Usual Standard of Care for Advanced Squamous Cell Lung Cancer (A Lung-MAP Treatment Trial) (clinicaltrials.gov) - P2; N=0; Withdrawn; Sponsor: Southwest Oncology Group; N=94 ➔ 0; Not yet recruiting ➔ Withdrawn

Clinical • Enrollment change • Trial withdrawal • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • KEAP1 • NFE2L2

Carboplatin and Paclitaxel With or Without Ramucirumab in Treating Patients With Locally Advanced, Recurrent, or Metastatic Thymic Cancer That Cannot Be Removed by Surgery (clinicaltrials.gov) - P2; N=66; Recruiting; Sponsor: Southwest Oncology Group; Trial completion date: Nov 2021 ➔ Nov 2022; Trial primary completion date: Nov 2020 ➔ Nov 2021

Clinical • Trial completion date • Trial primary completion date • Oncology • Solid Tumor • Thymic Carcinoma • Thymus Cancer

Phase 2 TaxRamPem for Patients With Metastatic or Recurrent NSCLC Who Progressed on Platinum-Doublet and PD-1/PD-L1 Blockade (clinicaltrials.gov) - P2; N=41; Recruiting; Sponsor: Emory University; Not yet recruiting ➔ Recruiting

Clinical • Enrollment open • IO Biomarker • Gastrointestinal Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Thoracic Cancer

Olaparib and Ramucirumab in Treating Patients With Metastatic or Locally Recurrent Gastric or Gastroesophageal Junction Cancer That Cannot Be Removed by Surgery (clinicaltrials.gov) - P1/2; N=49; Recruiting; Sponsor: National Cancer Institute (NCI); Trial completion date: Jun 2020 ➔ Jun 2021; Trial primary completion date: Jun 2020 ➔ Jun 2021

Clinical • Combination therapy • Trial completion date • Trial primary completion date • Esophageal Cancer • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • Oncology • Solid Tumor

Ramucirumab and Paclitaxel or FOLFIRI in Advanced Small Bowel Cancers (clinicaltrials.gov) - P2; N=94; Recruiting; Sponsor: Southwest Oncology Group; Not yet recruiting ➔ Recruiting; Initiation date: May 2020 ➔ Dec 2019

Clinical • Enrollment open • Trial initiation date • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor

Ramucirumab in Treating Patients With Advanced or Metastatic, Previously Treated Biliary Cancers That Cannot Be Removed by Surgery (clinicaltrials.gov) - P2; N=50; Recruiting; Sponsor: M.D. Anderson Cancer Center; Trial completion date: Dec 2019 ➔ Dec 2021; Trial primary completion date: Dec 2019 ➔ Dec 2020

Clinical • Trial completion date • Trial primary completion date • Biliary Cancer • Bladder Cancer • Cholangiocarcinoma • Gall Bladder Cancer • Gastrointestinal Cancer • Liver Cancer • Oncology • FGFR

Phase 2 TaxRamPem for Patients With Metastatic or Recurrent NSCLC Who Progressed on Platinum-Doublet and PD-1/PD-L1 Blockade (clinicaltrials.gov) - P2; N=41; Not yet recruiting; Sponsor: Emory University

Clinical • IO Biomarker • New P2 trial • Gastrointestinal Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Thoracic Cancer

Carboplatin and Paclitaxel With or Without Ramucirumab in Treating Patients With Locally Advanced, Recurrent, or Metastatic Thymic Cancer That Cannot Be Removed by Surgery (clinicaltrials.gov) - P2; N=66; Recruiting; Sponsor: Southwest Oncology Group; Trial completion date: Jun 2023 ➔ Nov 2021; Trial primary completion date: Jun 2022 ➔ Nov 2020

Clinical • Trial completion date • Trial primary completion date

Testing of TAK228 (MLN0128, Sapanisertib) Plus Docetaxel to the Usual Standard of Care for Advanced Squamous Cell Lung Cancer (A Lung-MAP Treatment Trial) (clinicaltrials.gov) - P2; N=94; Not yet recruiting; Sponsor: Southwest Oncology Group

Clinical • New P2 trial

Ramucirumab and Pembrolizumab Versus Standard of Care in Treating Patients With Stage IV or Recurrent Non-small Cell Lung Cancer (A Lung-MAP Non-Match Treatment Trial) (clinicaltrials.gov) - P2; N=144; Recruiting; Sponsor: Southwest Oncology Group

Clinical • New P2 trial

Impact of p53 status on TRAIL-mediated apoptotic and non-apoptotic signaling in cancer cells. (PubMed, PLoS One) - "Therefore, we analyzed side by side apoptotic and non-apoptotic signaling induced by TRAIL or the agonistic TRAIL-R-specific antibodies Mapatumumab (anti-TRAIL-R1) and Lexatumumab (anti-TRAIL-R2) in the two isogenic colon carcinoma cell lines HCT116 p53+/+ and p53-/-. In both cellular systems, we could clearly demonstrate the potentiating effects of p53 on TRAIL-R-mediated IL-8 induction. In conclusion, we found that wild-type p53 increases TRAIL-R-mediated apoptosis but simultaneously augments non-apoptotic signaling."

Journal

Ramucirumab and Paclitaxel or FOLFIRI in Advanced Small Bowel Cancers (clinicaltrials.gov) - P2; N=94; Not yet recruiting; Sponsor: Southwest Oncology Group

Clinical • New P2 trial

Ramucirumab and Pembrolizumab for the Treatment of EGFR Mutant Recurrent or Metastatic Non-small Cell Lung Cancer (clinicaltrials.gov) - P2; N=34; Not yet recruiting; Sponsor: Ohio State University Comprehensive Cancer Center

Clinical • New P2 trial • PD(L)-1 Biomarker

Olaparib and Ramucirumab in Treating Patients With Metastatic or Locally Recurrent Gastric or Gastroesophageal Junction Cancer That Cannot Be Removed by Surgery (clinicaltrials.gov) - P1/2; N=49; Recruiting; Sponsor: National Cancer Institute (NCI); Trial completion date: Jan 2019 ➔ Jun 2020; Trial primary completion date: Jan 2019 ➔ Jun 2020

Clinical • Combination therapy • PARP Biomarker • Trial completion date • Trial primary completion date