NC410 / NextCure - LARVOL DELTA

NC410 and FOLFIRINOX in Combination With Nivolumab With or Without Ipilimumab in Patients With Untreated Metastatic Pancreatic Cancer (clinicaltrials.gov) - P2 | N=20 | Recruiting | Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Not yet recruiting ➔ Recruiting

Enrollment open • Oncology • Pancreatic Cancer • Solid Tumor

NC410, a bivalent LAIR-2 construct, remodels collagen in the tumor microenvironment and abrogates neutrophil-driven T cell suppression. (PubMed, J Immunol) - "The proportion of collagen-1-positive cells was highest among tumor cells and tumor-infiltrating immune cells versus stromal immune cells, raising the potential role of tumor-associated collagen limiting immune cell infiltration into tumor. Our results support further evaluation of circulating and tumor-associated collagen products and LAIR-1 and LAIR-2 as prognostic biomarkers in advanced OC and as biomarkers for clinical response to NC410 and to other collagen- and LAIR-directed therapies."

Biomarker • Journal • Epithelial Ovarian Cancer • High Grade Serous Ovarian Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Solid Tumor • LAIR1

NC410 and FOLFIRINOX in Combination With Nivolumab With or Without Ipilimumab in Patients With Untreated Metastatic Pancreatic Cancer (clinicaltrials.gov) - P2 | N=20 | Not yet recruiting | Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

New P2 trial • Hepatology • Oncology • Pancreatic Cancer • Solid Tumor

KEYNOTE-D88: A Safety, Tolerability and Efficacy Study of NC410 Plus Pembrolizumab in Participants with Advanced Unresectable or Metastatic Solid Tumors (clinicaltrials.gov) - P1/2 | N=97 | Active, not recruiting | Sponsor: NextCure, Inc. | Recruiting ➔ Active, not recruiting | N=209 ➔ 97

Checkpoint inhibition • Enrollment change • Enrollment closed • Metastases • Cervical Cancer • Colorectal Cancer • Endometrial Cancer • Esophageal Cancer • Gastric Cancer • Head and Neck Cancer • Lung Cancer • Microsatellite Instability • Oncology • Ovarian Cancer • Solid Tumor • MSI

NC410 in combination with pembrolizumab improves anti-tumor responses by promoting collagen remodeling and tumor immunity in advanced ICI naïve MSS/MSI-L colorectal cancer (CRC) (SITC 2024) - P1/2 | "Progressive disease showed high baseline and early increase in neutrophils and Tregs, low baseline CD4+ effector population and early increase in PD-L1-expressing CD8+ T cells. Conclusions NC410 plus pembrolizumab shows promising durable clinical benefit in advanced metastatic MSS CRC by promoting collagen remodeling and tumor immunity.Download figure Open in new tab Download powerpoint Abstract 632 Figure 1 Volcano plot of changes in 34 protein levels on treatment (week 9) vs pre-treatment in tumor samples from patients with partial response, PR (A), stable disease, SD (B) and progression, PD (C); (GeoMx® DSP platform, CD45+ segments)"

Combination therapy • IO biomarker • Metastases • Colorectal Cancer • Gastrointestinal Cancer • Microsatellite Instability • Oncology • Solid Tumor • CD163 • CD8 • CEACAM8 • GZMB • LAIR1 • MSI • PTPRC

NextCure Reports…Additional Clinical Biomarker Data for NC410 Combo at Society for Immunotherapy of Cancer Annual Meeting (GlobeNewswire) - P1b/2 | N=209 | NCT05572684 | Sponsor: NextCure, Inc. | "The presentation includes additional clinical data for CRC patients from the Phase 1b portion of a Phase 1b/2 study evaluating NC410, a LAIR-2 fusion protein, in combination with pembrolizumab....Key findings: Of the 43 evaluable ICI-naïve MSS/MSI-L CRC patients without liver metastasis, there were 3 PRs as of the data cut-off of October 14, 2024. Disease control rates were 86% and 47% for the 200 mg and 100 mg NC410 doses, respectively. Biomarker data support proposed mechanism of action of NC410, showing remodeling of the tumor microenvironment, promotion of immune infiltration and anti-tumor activity. Treatment was well tolerated."

Biomarker • P1 data • Colorectal Cancer • Microsatellite Instability

Results of the phase Ib study of NC410 combined with pembrolizumab in ovarian cancer patients (ESMO 2024) - P1/2 | "NC410 in combination with pembrolizumab provides clinical benefit in advanced metastatic ovarian cancer, including those with liver metastasis."

Clinical • P1 data • Oncology • Ovarian Cancer • Solid Tumor • LAIR1 • MSI

Results of the phase Ib study of NC410 combined with pembrolizumab in MSS/MSI-L colorectal cancer patients (ESMO 2024) - P1/2 | "NC410 plus pembrolizumab combo is a well-tolerated treatment option with clinical benefit in hard-to-treat metastatic CRC that merits further evaluation in a randomized study."

Clinical • P1 data • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • CD8 • LAIR1 • MSI

NextCure Presented Results of the Phase 1b Study of NC410 in Combination with Pembrolizumab at ESMO 2024 (GlobeNewswire) - P1b/2 | N=209 | NCT05572684 | Sponsor; NextCure, Inc. | "The combination of NC410 and pembrolizumab continues to demonstrate clinical activity against ovarian cancer and MSS/MSI-L CRC, recalcitrant cancers that are generally unresponsive to immunotherapy. In both tumor types, study subjects who achieved clinical benefit of partial response or stable disease demonstrated durability of their responses that was clinically meaningful for these patient populations...We are continuing to follow the patients who remain on study and look forward to providing an update later this year."

P1 data • Colorectal Cancer • Microsatellite Instability • Ovarian Cancer

NextCure Provides Business Update and Reports Second Quarter 2024 Financial Results (GlobeNewswire) - "NC410 (LAIR-2 fusion): On track to present data from ongoing ovarian cancer cohort expansion along with an update on the CRC data in the fourth quarter of 2024; LNCB74 (B7-H4 ADC): Planned submission of an Investigational New Drug (IND) application by year-end."

IND • P1/2 data • Colorectal Cancer • Ovarian Cancer

KEYNOTE-D88: A Safety, Tolerability and Efficacy Study of NC410 Plus Pembrolizumab in Participants With Advanced Unresectable or Metastatic Solid Tumors (clinicaltrials.gov) - P1/2 | N=209 | Recruiting | Sponsor: NextCure, Inc. | N=131 ➔ 209

Checkpoint inhibition • Enrollment change • Metastases • Cervical Cancer • Colorectal Cancer • Endometrial Cancer • Esophageal Cancer • Gastric Cancer • Gastrointestinal Cancer • Head and Neck Cancer • Lung Cancer • Microsatellite Instability • Oncology • Ovarian Cancer • Solid Tumor • MSI

A phase 1b study of NC410 in combination with pembrolizumab in immune checkpoint inhibitor (ICI) naïve, and refractory microsatellite stable (MSS)/microsatellite instability-low (MSI-L) colorectal cancer (CRC) and ovarian cancer. (ASCO 2024) - P1/2 | "Taken together, NC410 in combination with pembrolizumab shows promising clinical activity in hard-to-treat, advanced metastatic CRC and Ovarian cancer."

Checkpoint inhibition • Combination therapy • P1 data • Cardiovascular • Colorectal Cancer • Fatigue • Gastrointestinal Cancer • Microsatellite Instability • Oncology • Ovarian Cancer • Refractory Ovarian Cancer • Solid Tumor • CD8 • LAIR1 • MSI

NextCure Presents Phase 1b Data on NC410 and Pembrolizumab Combination at ASCO 2024 (GlobeNewswire) - P1b/2 | N=131 | NCT05572684 | Sponsor: NextCure, Inc. | "NextCure...announced that clinical data from the Phase 1b portion of a Phase 1b/2 study evaluating NC410...in combination with pembrolizumab will be presented at the...ASCO Annual Meeting....Of the 37 evaluable ICI-naïve MSS/MSI-L CRC patients without liver metastasis treated with 100 mg of NC410, there were 2 confirmed ongoing PRs (12.5 months and 7.4 months) and 17 with stable disease. For this cohort, the median duration of disease control was 5.5 months, the disease control rate (DCR) was 51.3% [CI: 34.4, 68.1] and the overall response rate (ORR) was 5.4% [CI: 0.7, 18.2]. Of the 7 evaluable ovarian cancer patients in the 100 mg and 200 mg cohorts, there were 3 PRs {1 continued for 7.9 months (200 mg), 1 for 4.1 months (100 mg), and 1 ongoing at 5.1 months (100 mg)}. For this cohort, the DCR was 43% and ORR was 43%....'We look forward to reporting the results from the ongoing ovarian cancer cohort expansion later this year'."

P1 data • Colorectal Cancer • Microsatellite Instability • Ovarian Cancer

NextCure to Present Phase 1b Data of NC410 in Combination with Pembrolizumab at ASCO 2024 (GlobeNewswire) - "NextCure...announced that clinical trial investigator Eric S. Christenson, M.D., Assistant Professor of Oncology at Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, will present a poster on clinical data from the Phase 1b portion of a study evaluating NC410 in combination with pembrolizumab at the American Society of Clinical Oncology (ASCO) Annual Meeting..."

P1 data • Solid Tumor

NextCure Provides Business Update and Reports Full Year 2023 Financial Results (GlobeNewswire) - "NC410 for Ovarian Cancer: In March 2024, we commenced enrolling an additional 18 patients among the 100 mg and 200 mg cohorts. We plan to present the data from the ovarian cancer patients in the second half of 2024; NC410 Colorectal Cancer (CRC): Completed enrollment in January 2024 of an additional 20 patients in the 100 mg cohort. We plan to present the data of the CRC patients at a scientific conference within the second quarter of 2024."

P1/2 data • Trial status • Colorectal Cancer • Gynecologic Cancers • Microsatellite Instability • Ovarian Cancer • Solid Tumor

A Safety, Tolerability and Efficacy Study of NC410 Plus Pembrolizumab in Participants With Advanced Unresectable or Metastatic Solid Tumors (clinicaltrials.gov) - P1/2 | N=131 | Recruiting | Sponsor: NextCure, Inc. | Phase classification: P1b/2 ➔ P1/2

Phase classification • Cervical Cancer • Colorectal Cancer • Endometrial Cancer • Esophageal Cancer • Gastric Cancer • Gastrointestinal Cancer • Head and Neck Cancer • Lung Cancer • Microsatellite Instability • Oncology • Ovarian Cancer • Solid Tumor • MSI

Leukocyte-associated immunoglobulin-like receptor-1 blockade in combination with programmed death-ligand 1 targeting therapy mediates increased tumour control in mice. (PubMed, Cancer Immunol Immunother) - "However, combined targeting of LAIR-1 and PD-L1 results in increased tumour control. Thus, additional targeting of the LAIR-1:collagen pathway with NC410 is a promising approach to treating tumours where conventional immunotherapy is ineffective."

Combination therapy • IO biomarker • Journal • Preclinical • Oncology • LAIR1 • PD-L1

NextCure Provides Year-End Clinical Pipeline Updates (Yahoo Finance) - "The Phase 1b combination trial of NC410 with pembrolizumab is ongoing....Clinical data, including results from additional patients, are expected in the first half of 2024....Based on a comprehensive preclinical data package, we plan to initiate a dose range-finding toxicology study and GMP manufacturing for LNCB74 in early 2024. NC525 (LAIR-1 mAb): The Phase 1a dose escalation study in subjects with acute myeloid leukemia remains ongoing with the fourth cohort now enrolled....Clinical data are expected in the first half of 2024."

P1 data • Preclinical • Acute Myelogenous Leukemia • Colorectal Cancer • Gastrointestinal Cancer • Hematological Malignancies • Leukemia • Microsatellite Instability • Oncology • Solid Tumor

NextCure Provides Business Update and Reports Third Quarter 2023 Financial Results (GlobeNewswire) - "Q3 2023 Business Highlights and Updates: (i) Phase 1b updates for NC410 (LAIR-2 Fusion) and NC762 (B7-H4 mAb) by year end; (ii) Operational update for NC525 (LAIR-1 mAb) Phase 1a by year end."

P1 data • Trial status • Hematological Malignancies • Solid Tumor

A Safety and Tolerability Study of NC410 in Subjects With Advanced or Metastatic Solid Tumors (clinicaltrials.gov) - P1/2 | N=46 | Terminated | Sponsor: NextCure, Inc. | N=128 ➔ 46 | Trial completion date: Dec 2023 ➔ Jul 2023 | Active, not recruiting ➔ Terminated | Trial primary completion date: Dec 2023 ➔ Jul 2023; Upon completion of the Phase 1 portion of the NC410 monotherapy trial, NextCure focused efforts on a combination trial of NC410 in solid tumors.

Enrollment change • Metastases • Trial completion date • Trial primary completion date • Trial termination • Colorectal Cancer • Gastric Cancer • Gastrointestinal Cancer • Oncology • Ovarian Cancer • Solid Tumor

NextCure Provides Business Update and Reports Second Quarter 2023 Financial Results (GlobeNewswire) - "NC410 (LAIR-2 fusion): Continued enrollment in the Phase 1b/2 clinical trial evaluating NC410 in combination with pembrolizumab in patients with immune checkpoint naive or checkpoint refractory solid tumors; Phase 1b data are expected in the fourth quarter of 2023."

Enrollment status • P1 data • Oncology • Solid Tumor

NextCure Provides Business Update and Reports First Quarter 2023 Financial Results (GlobeNewswire) - "NextCure, Inc...today provided a business update and reported first quarter 2023 financial results. NC410 (LAIR-2 fusion): Continued enrollment in the Phase 1b/2 clinical trial evaluating NC410 in combination with pembrolizumab in patients with immune checkpoint refractory or naïve solid tumors. Phase 1b update is expected in the fourth quarter of 2023. NC762 (B7-H4 mAb): Continued enrollment in the Phase 1b dose expansion study in patients with solid tumors and high expression of B7-H4. Phase 1b update is expected in the fourth quarter of 2023. NC525 (LAIR-1 mAb)...Initial Phase 1a data are expected in the fourth quarter of 2023."

Enrollment status • P1 data • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • Solid Tumor

A Safety and Tolerability Study of NC410 in Subjects With Advanced or Metastatic Solid Tumors (clinicaltrials.gov) - P1/2 | N=128 | Active, not recruiting | Sponsor: NextCure, Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed • Metastases • Colorectal Cancer • Gastric Cancer • Gastrointestinal Cancer • Oncology • Ovarian Cancer • Solid Tumor

NextCure Provides Business Update and Reports Full Year 2022 Financial Results (GlobeNewswire) - "Business Highlights and Near-Term Milestones - NC410 (LAIR-2 fusion): (i) Continued enrollment in the Phase 1b/2 clinical trial evaluating NC410 in combination with pembrolizumab in patients with immune checkpoint refractory or naïve solid tumors; (ii) Phase 1b update is expected in mid-2023."

Enrollment status • P1 data • Cervical Cancer • Colorectal Cancer • Endometrial Cancer • Esophageal Cancer • Gastric Cancer • Gastroesophageal Cancer • Gastrointestinal Cancer • Gynecologic Cancers • Head and Neck Cancer • Lung Cancer • Microsatellite Instability • Oncology • Ovarian Cancer • Solid Tumor • Thoracic Cancer • Uterine Cancer

A phase 1b/2, open-label, safety, tolerability and efficacy study of NC410 plus pembrolizumab for participants with immune checkpoint inhibitor (ICI) refractory, or MSS/MSI-low ICI naïve advanced or metastatic solid tumors (SITC 2022) - "Objective response rate (ORR) based on RECIST v1.1 will be the primary endpoint, while duration of response (DoR), disease control rate (DCR), progression-free survival (PFS), and overall survival will be evaluated as secondary endpoints. Several biomarker effects of NC410 in combination with pembrolizumab in peripheral blood and tumor tissue will be assessed."

Checkpoint inhibition • Clinical • IO biomarker • P1/2 data • Endometrial Cancer • Gastric Cancer • Oncology • Solid Tumor • LAIR1 • MSI • TGFB1