cifurtilimab (SEA-CD40) / Pfizer - LARVOL DELTA

KEYNOTE-C86: A Study of SEA-CD40 Given With Other Drugs in Cancers (clinicaltrials.gov) - P2 | N=77 | Completed | Sponsor: Seagen Inc. | Active, not recruiting ➔ Completed | Trial completion date: Oct 2025 ➔ Nov 2024

Pan tumor • Trial completion • Trial completion date • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Solid Tumor • BRAF

Reversible Chemical Modification of Antibody Effector Function Mitigates Unwanted Systemic Immune Activation. (PubMed, Bioconjug Chem) - "The technology was applied to an effector function enhanced agonist CD40 antibody, SEA-CD40, and experiments demonstrate significant reductions in Fc-induced immune activation in vitro and in mice and nonhuman primates despite showing retained efficacy and improved pharmacokinetics compared to the parent antibody. We foresee that this simple, modular system can be rapidly applied to antibodies that suffer from systemic immune activation due to peripheral FcγR binding immediately upon infusion."

IO biomarker • Journal • Oncology • CD40

KEYNOTE-C86: A Study of SEA-CD40 Given With Other Drugs in Cancers (clinicaltrials.gov) - P2 | N=77 | Active, not recruiting | Sponsor: Seagen Inc. | Trial primary completion date: Oct 2024 ➔ Jan 2024

Combination therapy • Metastases • Pan tumor • Trial primary completion date • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Solid Tumor • BRAF

Harnessing the potential of CD40 agonism in cancer therapy. (PubMed, Cytokine Growth Factor Rev) - "In this review, we present the current understanding of the mechanism of action for CD40, along with results from the clinical development of agonistic human CD40 antibodies in cancer treatment (selicrelumab, CDX-1140, APX005M, mitazalimab, 2141-V11, SEA-CD40, LVGN7409, and bispecific antibodies). This review also examines the safety profile of CD40 agonists in both preclinical and clinical settings, highlighting optimized dosage levels, potential adverse effects, and strategies to mitigate them."

IO biomarker • Journal • Review • Oncology • CD40 • CD40LG • CD8 • TNFA

Phase 1 dose-escalation study of SEA-CD40: a non-fucosylated CD40 agonist, in advanced solid tumors and lymphomas. (PubMed, J Immunother Cancer) - P1 | "SEA-CD40 was tolerable as monotherapy and induced potent dose dependent immune cell activation and trafficking consistent with immune activation. Evidence of monotherapy antitumor activity was observed in patients with solid tumors and lymphoma. Further evaluation of SEA-CD40 is warranted, potentially as a component of a combination regimen."

IO biomarker • Journal • Metastases • P1 data • Basal Cell Carcinoma • Follicular Lymphoma • Head and Neck Cancer • Hematological Malignancies • Immune Modulation • Immunology • Lung Cancer • Lymphoma • Non-melanoma Skin Cancer • Oncology • Solid Tumor • CD40 • TNFA

Phase 1 dose-escalation study of SEA-CD40: a non-fucosylated CD40 agonist, in advanced solid tumors and lymphomas (J Immunother Cancer) - P1 | N=159 | NCT02376699 | Sponsor: Seagen Inc. | "A total of 67 patients received SEA-CD40 including 56 patients with solid tumors and 11 patients with lymphoma. A manageable safety profile was observed, with predominant adverse events of infusion/hypersensitivity reactions (IHRs) reported in 73% of patients....SEA-CD40 infusion resulted in potent immune activation, illustrated by dose dependent cytokine induction with associated activation and trafficking of innate and adaptive immune cells. Results suggested that doses of 10–30 µg/kg may result in optimal immune activation. SEA-CD40 monotherapy exhibited evidence of antitumor activity, with a partial response in a patient with basal cell carcinoma and a complete response in a patient with follicular lymphoma."

P1 data • Basal Cell Carcinoma • Follicular Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Non-melanoma Skin Cancer • Oncology • Skin Cancer • Solid Tumor

Updated results of a phase 1 study of SEA-CD40, gemcitabine, nab-paclitaxel, and pembrolizumab in patients with metastatic pancreatic ductal adenocarcinoma (PDAC; SGNS40-001). (ASCO-GI 2023) - P1 | "The combination of SEA-CD40 + GnP + pembro has an acceptable safety profile and shows evidence of antitumor activity in pts with PDAC. This regimen may warrant further evaluation. Clinical trial information: NCT02376699."

Clinical • Metastases • P1 data • Gastrointestinal Cancer • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • CD40

SGNS40-001: Safety Study of SEA-CD40 in Cancer Patients (clinicaltrials.gov) - P1 | N=159 | Terminated | Sponsor: Seagen Inc. | Trial completion date: Oct 2024 ➔ Apr 2023 | Active, not recruiting ➔ Terminated | Trial primary completion date: Jan 2024 ➔ Mar 2023; Study closed due to portfolio prioritization

Metastases • Trial completion date • Trial primary completion date • Trial termination • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Gastrointestinal Cancer • Head and Neck Cancer • Hematological Malignancies • Hodgkin Lymphoma • Indolent Lymphoma • Lung Cancer • Lymphoma • Melanoma • Non Small Cell Lung Cancer • Non-Hodgkin’s Lymphoma • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • CD40

KEYNOTE-C86: A Study of SEA-CD40 Given With Other Drugs in Cancers (clinicaltrials.gov) - P2 | N=77 | Active, not recruiting | Sponsor: Seagen Inc. | Recruiting ➔ Active, not recruiting | N=200 ➔ 77

Enrollment change • Enrollment closed • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Solid Tumor • BRAF

[VIRTUAL] Synergy Between SEA-CD40 and Chemotherapeutics Drives Curative Antitumor Activity in Preclinical Models (SITC 2020) - P1 | "A phase 1 clinical trial is actively enrolling (NCT02376699) and includes a cohort in pancreatic cancer assessing the combination of SEA-CD40, gemcitabine, nab-paclitaxel, and pembrolizumab. Ethics Approval Studies with human samples were performed according to institutional ethics standards. Animals studies were approved by and conducted in accordance with Seattle Genetics Institutional Care and Use Committee protocol #SGE-029."

Preclinical • Gastrointestinal Cancer • Oncology • Pancreatic Cancer • Solid Tumor • CD8

[VIRTUAL] Synergy Between SEA-CD40 and Chemotherapeutics Drives Curative Antitumor Activity in Preclinical Models (SITC 2020) - P1 | "A phase 1 clinical trial is actively enrolling (NCT02376699) and includes a cohort in pancreatic cancer assessing the combination of SEA-CD40, gemcitabine, nab-paclitaxel, and pembrolizumab. Ethics Approval Studies with human samples were performed according to institutional ethics standards. Animals studies were approved by and conducted in accordance with Seattle Genetics Institutional Care and Use Committee protocol #SGE-029."

Preclinical • Gastrointestinal Cancer • Oncology • Pancreatic Cancer • Solid Tumor • CD8

[VIRTUAL] SEA-CD40 is a non-fucosylated anti-CD40 antibody with potent pharmacodynamic activity in preclinical models and patients with advanced solid tumors (AACR-II 2020) - P1 | "These findings support continued clinical evaluation of SEA-CD40. The ongoing phase 1 clinical trial is actively enrolling and includes a cohort in pancreatic cancer assessing the combination of SEA-CD40, gemcitabine, nab-paclitaxel, and pembrolizumab."

PK/PD data • Gastrointestinal Cancer • Oncology • Pancreatic Cancer • Solid Tumor • CD8

Antitumor Activity Seen With CD40-Directed SEA-CD40 Combo in Pancreatic Ductal Adenocarcinoma (Targeted Oncology) - "'Patients with pancreas cancer need more and better treatments,' lead study author, Andrew L. Coveler, MD...said to OncLive. 'The combination of SEA-CD40, pembrolizumab, gemcitabine, and nab-paclitaxel compared favorably with historical controls, demonstrating that immunotherapy may 1 day be a treatment for patients with pancreas cancer.'"

Media quote

CD40-Directed SEA-CD40 Combo Denotes Antitumor Activity in Pancreatic Ductal Adenocarcinoma (OncLive) - "'Patients with pancreas cancer need more and better treatments,' lead study author, Andrew L. Coveler, MD...said to OncLive. 'The combination of SEA-CD40, pembrolizumab, gemcitabine, and nab-paclitaxel compared favorably with historical controls, demonstrating that immunotherapy may 1 day be a treatment for patients with pancreas cancer.'"

Media quote

CD40-Directed SEA-CD40 Combo Denotes Antitumor Activity in Pancreatic Ductal Adenocarcinoma (OncLive) - P1 | N=159 | NCT02376699 | Sponsor: Seagen Inc. | "The combination of SEA-CD40, gemcitabine, nab-paclitaxel (Abraxane), and pembrolizumab (Keytruda) demonstrated early evidence of efficacy in patients with metastatic pancreatic ductal adenocarcinoma (PDAC), according to updated results from the phase 1 SGNS40-001 study (NCT02376699) that were presented at the 2023 Gastrointestinal Cancers Symposium. As of August 16, 2022, with a median duration of exposure of 25.1 weeks, SEA-CD40 plus gemcitabine, nab-paclitaxel, and pembrolizumab showed a total confirmed objective response rate (ORR) of 44% (n = 27; 95% CI, 31.5%-57.6%), with comparable response rates observed at both evaluated dose levels of SEA-CD40. Patients who received the combination with SEA-CD40 at 10 µg/kg had a confirmed ORR of 48% (n = 19; 95% CI, 31.5%-63.9%), and those who received the combination with SEA-CD40 at 30 µg/kg had a confirmed ORR of 38% (n = 8; 95% CI, 18.1%-61.6%)."

P1 data • Gastrointestinal Cancer • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor

Safety Study of SEA-CD40 in Cancer Patients (clinicaltrials.gov) - P1 | N=159 | Active, not recruiting | Sponsor: Seagen Inc. | Trial primary completion date: Dec 2022 ➔ Jan 2024

Metastases • Trial primary completion date • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Gastrointestinal Cancer • Head and Neck Cancer • Hematological Malignancies • Hodgkin Lymphoma • Indolent Lymphoma • Lung Cancer • Lymphoma • Melanoma • Non Small Cell Lung Cancer • Non-Hodgkin’s Lymphoma • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • CD40

Phase 2 study of SEA-CD40 combination therapies in advanced malignancies (SGNS40-002, trial in progress) (SITC 2022) - P1, P2 | "Five indication-specific cohorts will explore 2 different regimens: cohorts 1–3 will receive SEA-CD40 with pembrolizumab while cohorts 4 and 5 will receive SEA-CD40, pembrolizumab, carboplatin, and pemetrexed. All patients will provide written informed consent. Consent All patients will provide written informed consent."

Combination therapy • IO biomarker • P2 data • Eye Cancer • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Uveal Melanoma • CD40 • TNFA

Preliminary results of a phase 1 study of sea-CD40, gemcitabine, nab-paclitaxel, and pembrolizumab in patients with metastatic pancreatic ductal adenocarcinoma (PDAC). (ASCO-GI 2022) - P1 | "We present data from an ongoing Phase 1 study (SGNS40-001) in a PDAC cohort evaluating the combination of SEA-CD40, GnP, and pembrolizumab (pembro). The combination of SEA-CD40 + GnP + pembro demonstrated a tolerable safety profile. Evidence of immune activation was observed, consistent with the proposed mechanism of action. Follow-up for response and survival are ongoing."

Clinical • IO biomarker • P1 data • Gastrointestinal Cancer • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • CD40 • CD8

A Study of SEA-CD40 Given with Other Drugs in Cancers (clinicaltrialsregister.eu) - P2; N=200; Ongoing; Sponsor: Seagen Inc.

Clinical • Combination therapy • New P2 trial • Pan tumor • Eye Cancer • Genetic Disorders • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Melanoma • Non Small Cell Lung Cancer • Ocular Melanoma • Oncology • Skin Cancer • Solid Tumor • BRAF • PD-L2

A Study of SEA-CD40 Given With Other Drugs in Cancers (clinicaltrials.gov) - P2; N=200; Recruiting; Sponsor: Seagen Inc.; Not yet recruiting ➔ Recruiting

Clinical • Combination therapy • Enrollment open • Pan tumor • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Solid Tumor • BRAF

Safety Study of SEA-CD40 in Cancer Patients (clinicaltrials.gov) - P1 | N=159 | Active, not recruiting | Sponsor: Seagen Inc. | Trial completion date: Jun 2024 ➔ Oct 2024 | Trial primary completion date: Jun 2022 ➔ Dec 2022

Trial completion date • Trial primary completion date • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Gastrointestinal Cancer • Head and Neck Cancer • Hematological Malignancies • Hodgkin Lymphoma • Indolent Lymphoma • Lung Cancer • Lymphoma • Melanoma • Non Small Cell Lung Cancer • Non-Hodgkin’s Lymphoma • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • CD40

Seagen Reports Data From SEA-CD40 in Combination With Other Therapies in Metastatic Pancreatic Ductal Adenocarcinoma (PDAC) at the American Society of Clinical Oncology Gastrointestinal Cancers Symposium (ASCO GI) (Businesswire) - P1, N=159; NCT02376699; Sponsor: Seagen Inc.; "Seagen...announced data from a phase 1 clinical trial combining SEA-CD40 with chemotherapy and an anti-PD-1 in patients with metastatic PDAC at the ASCO GI annual meeting taking place in San Francisco, January 20 – 22, 2022....Activity of SEA-CD40 in combination with GnP and pembrolizumab was observed in both doses of SEA-CD40 tested. The overall (N = 61) cORR was 44 percent, median PFS was 7.4 months (95 percent CI: 5.6-9.0), and median OS was 15.0 months (95 percent CI: 7.8-19.9)."

P1 data • Gastrointestinal Cancer • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Solid Tumor

Safety Study of SEA-CD40 in Cancer Patients (clinicaltrials.gov) - P1 | N=159 | Active, not recruiting | Sponsor: Seagen Inc. | Trial completion date: Feb 2024 ➔ Jun 2024 | Trial primary completion date: Feb 2022 ➔ Jun 2022

Trial completion date • Trial primary completion date • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Gastrointestinal Cancer • Head and Neck Cancer • Hematological Malignancies • Hodgkin Lymphoma • Indolent Lymphoma • Lung Cancer • Lymphoma • Melanoma • Non Small Cell Lung Cancer • Non-Hodgkin’s Lymphoma • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • CD40

[VIRTUAL] Phase I study of SEA-CD40, gemcitabine, nab-paclitaxel, and pembrolizumab in patients with metastatic pancreatic ductal adenocarcinoma (PDAC). (ASCO 2020) - P1 | "An ongoing Phase 1 study (SGNS40-001) is evaluating SEA-CD40 as monotherapy and in combination with pembrolizumab in patients with advanced solid or hematologic malignancies. Enrollment to this cohort began in November 2019. Research Funding: Seattle Genetics, Inc."

Clinical • P1 data • Hematological Malignancies • Immune Modulation • Inflammation • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • CD40

[VIRTUAL] Phase I study of SEA-CD40, gemcitabine, nab-paclitaxel, and pembrolizumab in patients (pts) with metastatic pancreatic ductal adenocarcinoma (PDAC) (trial in progress). (ASCO-GI 2021) - "A Phase 1 study (SGNS40-001) is evaluating SEA-CD40 monotherapy and in combination with other agents in pts with advanced solid or hematologic malignancies. Assessment of dose-limiting toxicity will occur initially in groups of 6 pts to identify the recommended phase 2 dose of SEA-CD40 for the cohort. Enrollment to this cohort began in November 2019."

Clinical • P1 data • Gastrointestinal Cancer • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma