navicixizumab (OMP-305B83) / Mereo Biopharma, Feng Biosciences - LARVOL DELTA

Delta-like Ligand 4 Inhibitors Induce Pulmonary Arterial Hypertension in Clinical Trials (AHA 2024) - "The most common antibody used was Demcizumab(6), followed by Navicixizumab(2), Dilpacimab(2), ABL001(2), and Enoticumab(1). DLL-4 inhibition treatment for malignancies has demonstrated PAH as a side effect. These results are in accordance with our previous observation that unopposed JAG-1-NOTCH3 signaling, induces pulmonary vascular SMC proliferation and PAH. Discontinuation of DLL-4 inhibitors leads to resolution of disease."

Clinical • Cardiovascular • Oncology • Pulmonary Arterial Hypertension • Respiratory Diseases • NOTCH3

Phase Ib Study of Navicixizumab Plus Paclitaxel in Patients With Platinum-Resistant Ovarian, Primary Peritoneal, or Fallopian Tube Cancer. (PubMed, J Clin Oncol) - "Navicixizumab plus paclitaxel demonstrated promising clinical activity in bevacizumab-treated and -naive patients with platinum-resistant ovarian cancer, with manageable toxicity."

Journal • P1 data • Fallopian Tube Cancer • Hematological Disorders • Hypertension • Neutropenia • Oncology • Ovarian Cancer • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases • Solid Tumor • Thrombocytopenia

"great presentation. curious to know how does Navicixizumab compare to CTX-009 anti-DLL4/VEGF bispecific antibody" (@ej23ny)

Mereo BioPharma Reports Full Year 2022 Financial Results and Recent Highlights (GlobeNewswire) - "Navicixizumab (OMP305B83): (i) Following regulatory interactions, Mereo’s partner, OncXerna, has stated its intention to initiate a Phase 3 trial of navicixizumab in late line ovarian cancer; (ii) OncXerna is also dosing patients in a Phase 2 basket study evaluating navicixizumab, alone or in combination with chemotherapy, in patients with select advanced solid tumors."

New P3 trial • Trial status • Gynecologic Cancers • Oncology • Ovarian Cancer • Solid Tumor

A biomarker study of the bispecific anti-DLL4/anti-VEGF antibody navicixizumab (OMP-305B83) in Phase 1a patients with previously treated solid tumors (EORTC-NCI-AACR 2018) - P1; "Biomarker analysis of pts from the Phase1a trial of navicixizumab in previously treated solid tumors demonstrated target engagement of both DLL4 and VEGF. Significant modulation of Notch and VEGF pathway genes by navicixizumab was observed in surrogate tissues. Updated biomarker results will be presented."

Biomarker • Clinical • P1 data • Gynecologic Cancers • Ovarian Cancer • Solid Tumor

A phase1b study of navicixizumab plus FOLFIRI in second-line treatment of patients with metastatic colorectal cancer. (ASCO-GI 2023) - "This study was stopped early to focus on the development of navicixizumab in ovarian cancer. Although the disease control rate was promising, further evaluation is needed to determine whether navicixizumab delivers efficacy greater than chemotherapy alone and assess tolerability of this regimen. >"

Clinical • Metastases • P1 data • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor

ONCX-NAV-G201: A phase 2 basket study of navicixizumab monotherapy or in combination with chemotherapy in patients with select advanced solid tumors—Colorectal Cancer Cohort (trial in progress). (ASCO-GI 2023) - P2 | "Up to 30 patients will be enrolled to each CRC cohort from approximately 8 sites in the US and will receive 3 mg/kg navicixizumab alone (Cohort A1) or in combination with irinotecan (180 mg/m2 on Days 1 and 15 of a 28-day cycle, Cohort A2). Secondary efficacy endpoints include overall survival, time to response, disease control rate, duration of response, and the relationship between antitumor activity of navicixizumab and Xerna TME Panel biomarker subtypes. Clinical trial information: NCT05453825."

Clinical • Combination therapy • Metastases • Monotherapy • P2 data • Pan tumor • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor

ONCX-NAV-G201: A phase 2, basket study of navicixizumab monotherapy or in combination with chemotherapy in patients with select advanced solid tumors: Triple-negative breast cancer cohort (trial in progress) (SABCS 2022) - " Eligible TNBC patients will have locally advanced or metastatic disease and have received at least 2 and no more than 4 prior lines of standard therapy for metastatic disease, including immunotherapy (for PD-L1 positive TNBC patients), and sacituzumab govitecan...Up to 30 patients will be enrolled to each TNBC cohort from approximately 8 sites in the US and will receive 3 mg/kg navicixizumab alone (Cohort C1) or in combination with paclitaxel (80 mg/m2 on Days 1, 8, and 15 of a 28-day cycle) (Cohort C2)...Cohort continuation and future evaluation decisions will be guided by the boundaries identified by a sequential monitoring procedure. Secondary efficacy endpoints include overall survival, time to response, disease control rate, duration of response, and the relationship between antitumor activity of navicixizumab and Xerna TME Panel™ biomarker subtypes."

Clinical • Combination therapy • IO biomarker • Monotherapy • P2 data • Pan tumor • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • HER-2

"A11: Navicixizumab phase I in #CRCSM #CRCTrialsChat" (@IglesiaMichael)

P1 data • Colorectal Cancer

"But this is not about navicixizumab, is it? $MREO" (@wkissel)

Correlative analyses of phase 1b study of navicixizumab plus paclitaxel in patients with platinum resistant ovarian cancer using xerna™ TME panel (ESGO 2021) - "Patients received a median of 4 prior treatments (63% prior bevacizumab, 45% prior PARP). Conclusion* Navicixizumab plus paclitaxel demonstrated promising clinical activity in this heavily pretreated patient population. The Xerna™ TME Panel may identify patients more likely to benefit from treatment with navicixizumab and should be prospectively evaluated in a future study."

Clinical • P1 data • Oncology • Ovarian Cancer • Solid Tumor • PARP1

[VIRTUAL] A phase Ib study of navicixizumab and weekly paclitaxel in heavily pretreated platinum resistant ovarian, primary peritoneal or fallopian tube cancer (SGO-I 2020) - "This is an ongoing phase 1b study designed to assess the safety and efficacy of paclitaxel and navicixizumab in platinum-resistant ovarian cancer patients who received at least 3 prior therapies and/or bevacizumab. These interim efficacy data in heavily pretreated platinum-resistant ovarian cancer patients are encouraging. The safety profile appears to be manageable with hypertension being the most common adverse event related to navicixizumab. Final data will be presented."

P1 data • Fallopian Tube Cancer • Fatigue • Gynecologic Cancers • Hematological Disorders • Hypertension • Neutropenia • Oncology • Ovarian Cancer • Pulmonary Arterial Hypertension • Thrombocytopenia • CA125

Phase 2 Trial to Study Novel Drug in Pretreated Solid Tumors (Cure Today) - "The trial, which is currently open for enrollment in six cancer centers across the United States, will start with two groups. One will be analyzing navicixizumab alone or in combination with irinotecan for patients with colorectal cancer that has failed two lines of prior standard therapy, including Avastin (bevacizumab) or an equivalent antibody. The other will evaluate navicixizumab alone or in combination with paclitaxel for patients with triple-negative breast cancer who received between two and four standard lines of therapy for metastatic disease, including an immune checkpoint inhibitor or Trodelvy (sacituzumab govitecan)....Researchers plan on adding another two groups to the trial in the future — one investigating the drug in as a monotherapy in pretreated, relapsed/refractory ovarian cancer and the other looking at navicixizumab plus paclitaxel in patients with gastric or gastroesophageal cancer that has previously been treated with an immune checkpoint inhibitor."

Clinical protocol • Breast Cancer • Colorectal Cancer • Gastric Cancer • Gastroesophageal Cancer • Gastrointestinal Cancer • Gynecologic Cancers • Oncology • Ovarian Cancer • Solid Tumor • Triple Negative Breast Cancer

OncXerna Therapeutics Doses First Patient in Phase 2 Trial Evaluating Navicixizumab Alone or in Combination with Chemotherapy in Patients with Select Advanced Solid Tumors (GlobeNewswire) - "OncXerna Therapeutics...announced the initiation of dosing in a Phase 2 basket trial evaluating the anti-DLL4/VEGF bispecific antibody navicixizumab, alone or in combination with chemotherapy, in patients with select advanced solid tumors. The trial is a multicenter, open-label, signal finding study with cohorts in colorectal and triple negative breast cancer currently open for enrollment. The colorectal cancer cohort is evaluating navicixizumab alone and in combination with irinotecan, while the triple negative breast cancer cohort is evaluating navicixizumab alone and in combination with paclitaxel."

Trial status • Breast Cancer • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer

A Study of Navicixizumab in Patients With Platinum Resistant Ovarian Cancer (clinicaltrials.gov) - P3 | N=400 | Not yet recruiting | Sponsor: OncXerna Theraputics, Inc. | Initiation date: Jun 2022 ➔ Nov 2022

Monotherapy • Trial initiation date • Fallopian Tube Cancer • Oncology • Ovarian Cancer • Peritoneal Cancer • Solid Tumor

A Study of Navicixizumab Monotherapy or in Combination in Patients With Select Advanced Solid Tumors (clinicaltrials.gov) - P2 | N=180 | Recruiting | Sponsor: OncXerna Theraputics, Inc. | Not yet recruiting ➔ Recruiting

Combination therapy • Enrollment open • Monotherapy • Pan tumor • Breast Cancer • Colon Cancer • Colorectal Adenocarcinoma • Colorectal Cancer • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • Oncology • Ovarian Cancer • Solid Tumor • Triple Negative Breast Cancer

A Study of Navicixizumab Monotherapy or in Combination in Patients With Select Advanced Solid Tumors (clinicaltrials.gov) - P2 | N=180 | Not yet recruiting | Sponsor: OncXerna Theraputics, Inc.

Combination therapy • Monotherapy • New P2 trial • Pan tumor • Breast Cancer • Colon Cancer • Colorectal Adenocarcinoma • Colorectal Cancer • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • Oncology • Ovarian Cancer • Solid Tumor • Triple Negative Breast Cancer

A Study of Navicixizumab in Patients With Platinum Resistant Ovarian Cancer (clinicaltrials.gov) - P3 | N=400 | Not yet recruiting | Sponsor: OncXerna Theraputics, Inc. | Initiation date: Nov 2021 ➔ Jun 2022

Monotherapy • Trial initiation date • Fallopian Tube Cancer • Oncology • Ovarian Cancer • Peritoneal Cancer • Solid Tumor

Navicixizumab plus Paclitaxel Shows Clinical Benefit in Platinum-Resistant Ovarian Cancer. (PubMed, Cancer Discov) - "Combined navicixizumab and paclitaxel showed durable activity in patients with platinum-resistant ovarian cancer."

Journal • Oncology • Ovarian Cancer • Solid Tumor

OncXerna Therapeutics Announces Journal of Clinical Oncology Publication Featuring Phase 1b Data of Navicixizumab Plus Paclitaxel in Ovarian Cancer (OncXerna Therapeutics Press Release) - P1b | N=44 | NCT03030287 | Sponsor: OncoMed Pharmaceuticals, Inc | "Navicixizumab plus paclitaxel showed promising and durable clinical activity in a heavily pretreated patient population regardless of prior treatment (median of four prior therapies) Overall response rate (ORR) across all evaluable patients: 43% (19/44), ORR in patients previously treated with bevacizumab (Avastin®): 33% (10/30), ORR in patients previously treated with a PARP inhibitor: 45% (9/20),11 of 19 patients with partial or complete response had progressive disease as best response to immediate prior therapy. Median duration of response: 6 months. B+ classification showed enrichment of patients with tumor response. ORR in B+ vs. B- patients: 62% (8/13) vs. 25% (5/20), Best response of progressive disease in B+ vs. B- patients: 0% (0/13) vs. 30% (6/20), Median progression-free survival in B+ vs. B- patients: 9.2 months vs. 3.9 months."

P1 data • Gynecologic Cancers • Oncology • Ovarian Cancer

Furthering the clinical development of navicixizumab in advanced epithelial ovarian cancer patients with a population pharmacokinetic model and exploratory exposure-safety-efficacy response analyses (SGO 2022) - "Learning Objective: Conclude that the current clinical data with navicixizumab support its continued development in ovarian cancer patients."

Clinical • PK/PD data • Oncology • Ovarian Cancer • Solid Tumor

Study of Navicixizumab Plus Paclitaxel and Navicixizumab Monotherapy in Comparison to Paclitaxel Monotherapy in Patients with Platinum-Resistant Epithelial Ovarian, Primary Peritoneal, or Fallopian Tube Cancer Estudio de Navicixizumab con paclitaxel y navicixizumab en monoterapia en comparación con paclitaxel en monoterapia en pacientes con cáncer de ovario epitelial resistente al platin (clinicaltrialsregister.eu) - P3; N=400; Ongoing; Sponsor: OncXerna Therapeutics, Inc.

Clinical • Monotherapy • New P3 trial • Endometrial Cancer • Fallopian Tube Cancer • Oncology • Ovarian Cancer • Solid Tumor • BRCA • BRCA1

OncXerna Therapeutics Announces New Biomarker Data from Retrospective Analysis of Results from Phase 1b Ovarian Cancer Trial of Navicixizumab Plus Paclitaxel at the ESGO 2021 Congress (OncXerna Therapeutics Press Release) - P1b, N=NA; "'There is a pressing unmet need for new treatments for patients with platinum-resistant ovarian cancer who have progressed on Avastin® or failed more than two lines of prior therapy,' said Dr. Kathleen Moore...'I believe the data presented at ESGO demonstrated the potential of navicixizumab together with the Xerna TME Panel to help address this need. The response rate and treatment durability of navicixizumab in this heavily pretreated patient population are very exciting and results showed improved outcomes in patients classified as having a high angiogenesis score by the Xerna TME Panel's novel, RNA-expression based algorithm. We have been searching for a predictive biomarker for anti-angiogenic therapies and the Xerna TME panel results presented at ESGO are very promising.'"

Biomarker • Retrospective data

OncXerna Therapeutics Announces New Biomarker Data from Retrospective Analysis of Results from Phase 1b Ovarian Cancer Trial of Navicixizumab Plus Paclitaxel at the ESGO 2021 Congress (GlobeNewswire) - "OncXerna Therapeutics...today announced new biomarker data from a retrospective analysis of results from its Phase 1b clinical trial of navicixizumab in an electronic poster at the European Society of Gynaecological Oncology (ESGO) Congress 2021....Data presented in the poster are from a retrospective analysis of results from an open-label Phase 1b trial evaluating navicixizumab, a potentially first-in-class anti-DLL4/VEGF bispecific antibody targeting tumor vasculature, in combination with paclitaxel in patients with platinum-resistant ovarian cancer (PROC)....Clinical outcomes were greater in biomarker positive (B+) vs. biomarker negative (B-) patients. Overall response rate (ORR) in B+ patients: 62% (8/13)....A consistent correlation was seen between B+ subtype and improved progression-free survival (PFS). Median PFS in B+ patients: 9.2 months (95% confidence interval: 5.5 – not estimable)."

Biomarker • Retrospective data • Gynecologic Cancers • Oncology • Ovarian Cancer

A Phase 1b Study of Navicixizumab & Weekly Paclitaxel in Heavily Pre-Treated Platinum Resistant Ovarian, Primary Peritoneal or Fallopian Tube Cancer. (ESMO 2018) - P1b; " This is an ongoing Phase 1b study of paclitaxel & navicixizumab in platinum resistant ovarian cancer pts who have failed > 2 prior therapies &/or bevacizumab. The efficacy data in these heavily pre-treated platinum resistant ovarian cancer pts are encouraging & enrollment is ongoing. The safety profile appears to be manageable with hypertension being the most common adverse event related to navicixizumab."

P1 data • Ovarian Cancer