sotigalimab (PYX-107) / Pyxis Oncology - LARVOL DELTA

A Phase 2 Study of Sotigalimab, a CD40 Agonist Antibody, Plus Concurrent Chemoradiation as Neoadjuvant Therapy for Esophageal and Gastroesophageal Junction Cancers. (PubMed, Cancer Res Commun) - P2 | "Sotigalimab combined with NCRT for esophageal or GEJ cancers was generally well tolerated and achieved path CR rates that compare favorably to historical data and are promising for this treatment strategy."

Journal • P2 data • Cervical Cancer • Esophageal Cancer • Fatigue • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Oncology • Solid Tumor • Squamous Cell Carcinoma • CD40

Outcomes and Immune Responses from INNATE: A Randomized Phase II Trial of Sotigalimab Immunotherapy during Neoadjuvant Therapy of Rectal Cancer (ASTRO 2024) - P2 | "Adding Sotiga to SCRT and CT in LARC appears to be safe and shows robust responses to unfavorable disease, with evidence of increased antitumor adaptive immune responses compared to SCRT alone. Disease control outcomes are pending."

Clinical • IO biomarker • Late-breaking abstract • P2 data • Cardiovascular • Colorectal Cancer • Gastrointestinal Cancer • Infectious Disease • Oncology • Pain • Rectal Cancer • Septic Shock • Solid Tumor • CD40 • CD8 • GZMB • GZMK • IL2 • NKG7 • PRF1

Sotigalimab and/or nivolumab with chemotherapy in first-line metastatic pancreatic cancer: clinical and immunologic analyses from the randomized phase 2 PRINCE trial. (PubMed, Nat Med) - P1b/2 | "We conducted a randomized phase 2 trial evaluating the efficacy of nivolumab (nivo; anti-PD-1) and/or sotigalimab (sotiga; CD40 agonistic antibody) with gemcitabine/nab-paclitaxel (chemotherapy) in patients with first-line metastatic PDAC ( NCT03214250 ). A patient subset benefitting from sotiga/nivo/chemo was not identified. Collectively, these analyses suggest potential treatment-specific correlates of efficacy and may enable biomarker-selected patient populations in subsequent PDAC chemoimmunotherapy trials."

IO biomarker • Journal • P2 data • Gastrointestinal Cancer • Hepatology • Immune Modulation • Immunology • Inflammation • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • CD40

Tumor Microenvironment Characterization and Outcome Prediction in Concurrent Radiation Therapy and Immunotherapy Using CODEX (ASTRO 2025) - P2 | "The treatment included short-course radiotherapy (SCRT), the CD40 agonist sotigalimab (Sotiga), and FOLFOX chemotherapy... Our approach offers a framework leveraging spatial and interaction-based cellular features with CODEX, making it a valuable tool for investigating the biological evidence of synergistic effects between radiation and immunotherapy, as well as for biologically informed outcome prediction. Future work will aim to expand this methodology to larger datasets and integrate CODEX-based features with standard image-based radiomics."

Biomarker • IO biomarker • Tumor microenvironment • Colorectal Cancer • Oncology • Rectal Cancer • Solid Tumor • CD8

Phase I Study of APX005M in Pediatric Central Nervous System Tumors (clinicaltrials.gov) - P1 | N=32 | Completed | Sponsor: Pediatric Brain Tumor Consortium | Active, not recruiting ➔ Completed

Trial completion • Astrocytoma • Brain Cancer • CNS Tumor • Diffuse Intrinsic Pontine Glioma • Ependymoma • Germ Cell Tumors • Glioblastoma • Glioma • Medulloblastoma • Oncology • Pediatrics • Solid Tumor • CD4 • TMB

Pediatric Brain Tumor Consortium phase 1 study of CD40 agonist sotigalimab in pediatric and young adult patients with recurrent CNS tumors and newly-diagnosed DIPG. (PubMed, Clin Cancer Res) - "Sotigalimab was well-tolerated in pediatric patients with recurrent or progressive CNS tumors and post-radiation pre-progression DIPG."

Journal • P1 data • Brain Cancer • CNS Tumor • Diffuse Intrinsic Pontine Glioma • Glioma • Oncology • Pediatrics • Solid Tumor • CD40

Personalized Peptide Vaccine in Treating Patients With Advanced Pancreatic Cancer or Colorectal Cancer (clinicaltrials.gov) - P1 | N=300 | Enrolling by invitation | Sponsor: M.D. Anderson Cancer Center | Recruiting ➔ Enrolling by invitation

Enrollment status • Colorectal Adenocarcinoma • Colorectal Cancer • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • CA 19-9

Switch Maintenance in Pancreatic (clinicaltrials.gov) - P1/2 | N=46 | Suspended | Sponsor: James Cleary, MD, PhD | Trial completion date: Sep 2028 ➔ May 2032 | Trial primary completion date: Jan 2027 ➔ May 2026

Trial completion date • Trial primary completion date • Oncology • Pancreatic Cancer • Solid Tumor • Squamous Cell Carcinoma

A Study of APX005M in Combination With Nivolumab and Ipilimumab in Treatment Naïve Patients With Advanced Melanoma or Renal Cell Carcinoma (RCC) (clinicaltrials.gov) - P1 | N=26 | Completed | Sponsor: Yale University | Active, not recruiting ➔ Completed | Trial completion date: Aug 2026 ➔ Mar 2026

Trial completion • Trial completion date • Genito-urinary Cancer • Melanoma • Oncology • Renal Cell Carcinoma • Solid Tumor

APX005M and Doxorubicin in Advanced Sarcoma (clinicaltrials.gov) - P2 | N=27 | Completed | Sponsor: Alexander Z. Wei, MD | Trial completion date: Dec 2026 ➔ Dec 2025 | Trial primary completion date: Dec 2026 ➔ Dec 2025 | Active, not recruiting ➔ Completed

Trial completion • Trial completion date • Trial primary completion date • Oncology • Sarcoma • Soft Tissue Sarcoma • Solid Tumor

INNATE: Immunotherapy During Neoadjuvant Therapy for Rectal Cancer (clinicaltrials.gov) - P2 | N=58 | Completed | Sponsor: University of Texas Southwestern Medical Center | Active, not recruiting ➔ Completed

Trial completion • Colorectal Adenocarcinoma • Colorectal Cancer • Oncology • Rectal Adenocarcinoma • Rectal Cancer • Solid Tumor

Personalized Peptide Vaccine in Treating Patients With Advanced Pancreatic Cancer or Colorectal Cancer (clinicaltrials.gov) - P1 | N=300 | Recruiting | Sponsor: M.D. Anderson Cancer Center | Active, not recruiting ➔ Recruiting | N=117 ➔ 300

Enrollment change • Enrollment open • Colorectal Adenocarcinoma • Colorectal Cancer • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • CA 19-9

Trial in progress: A phase I study of personalized neoantigen vaccination combined with PD-1 blockade and CD40 agonism in resected pancreatic ductal adenocarcinoma (AACR 2026) - P1 | "However, PDAC has a profoundly "cold," immunosuppressive microenvironment that can limit effective priming and durability of vaccine-induced antitumor immunity, supporting rational combinations with PD-1 blockade and CD40 agonism to enhance antigen presentation and reinvigorate effector function. This study is a single-center, non-randomized, open-label, investigator-initiated phase 1 trial of NeoAg-VAX in combination with anti-PD-1 pembrolizumab +/- CD40 agonist APX005M in patients with surgically resected PDAC...Vaccines are given subcutaneously (SQ) with topical imiquimod adjuvant and APX005M (0.3 mg/kg IV + 250 μg SQ) on weeks 0, 1, 3, 4, 6, 9, 12, 15, 18, 21, and 24...Translational studies evaluating vaccine-induced ctDNA dynamics and functional neoantigen-specific T cell responses are in progress. As of January 2026, 6 patients have been vaccinated in this cohort with follow-up and analyses ongoing (NCT02600949)."

P1 data • Tumor-specific neoantigens • Colorectal Cancer • Oncology • Pancreatic Ductal Adenocarcinoma • CD40

Intratumoral sotigalimab with pembrolizumab induces rapid activation of antigen presenting cells and drives anti-tumor responses in non-injected tumors in metastatic melanoma: A phase I/II study. (PubMed, Cancer Discov) - P1/2 | "TCR sequencing showed increased T-cell clonality with expanded new clones shared across tumors. Clinical responses correlated with these immunologic changes, but not with baseline features associated with response to anti-PD1 monotherapy."

Journal • P1/2 data • Melanoma • Oncology • Solid Tumor • ITGAX • LAMP3

Intratumoral sotigalimab with pembrolizumab induces rapid activation of antigen presenting cells and drives anti-tumor responses in non-injected tumors in metastatic melanoma: A phase I/II study (AACR 2026) - P1/2 | "Clinical responses correlated with these immunologic changes, but not with baseline immunological features associated with response to anti-PD1 monotherapy. These findings suggest that intratumoral sotigalimab may enhance anti-PD1 therapy, supporting the need for further randomized phase 2 trials to better evaluate its therapeutic potential in the 'in situ' immunization approach."

IO biomarker • Metastases • P1/2 data • Melanoma • Oncology • Solid Tumor • ITGAX • LAMP3

Switch Maintenance in Pancreatic (clinicaltrials.gov) - P1/2 | N=46 | Suspended | Sponsor: James Cleary, MD, PhD | Trial primary completion date: Jan 2026 ➔ Jan 2027

Trial primary completion date • Oncology • Pancreatic Cancer • Solid Tumor • Squamous Cell Carcinoma

Phase I Study of APX005M in Pediatric Central Nervous System Tumors (clinicaltrials.gov) - P1 | N=32 | Active, not recruiting | Sponsor: Pediatric Brain Tumor Consortium | Trial completion date: Nov 2025 ➔ Jun 2026

Trial completion date • Astrocytoma • Brain Cancer • CNS Tumor • Diffuse Intrinsic Pontine Glioma • Ependymoma • Germ Cell Tumors • Glioblastoma • Glioma • Medulloblastoma • Oncology • Pediatrics • Solid Tumor • CD4 • TMB

Switch Maintenance in Pancreatic (clinicaltrials.gov) - P1/2 | N=46 | Suspended | Sponsor: James Cleary, MD, PhD | Recruiting ➔ Suspended

Trial suspension • Oncology • Pancreatic Cancer • Solid Tumor • Squamous Cell Carcinoma

Personalized Peptide Vaccine in Treating Patients With Advanced Pancreatic Cancer or Colorectal Cancer (clinicaltrials.gov) - P1 | N=117 | Active, not recruiting | Sponsor: M.D. Anderson Cancer Center | Enrolling by invitation ➔ Active, not recruiting

Enrollment closed • Colorectal Adenocarcinoma • Colorectal Cancer • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • CA 19-9

CAR-T triggers TAM reeducation and adaptive anti-tumor response via TREM2 deficiency or CD40 agonist. (PubMed, Cell Rep Med) - "Notably, the clinical agonist sotigalimab similarly enhances human CD8+ T cell migration in vitro. Our findings highlight the significance of combining GPC3-CAR-T therapy with CD40 agonist as a critical pre-requisite for eliciting reeducation of TAMs and enhancing the efficacy of CAR-T therapy in HCC."

IO biomarker • Journal • Hepatocellular Cancer • Oncology • Solid Tumor • CD40 • CD8 • CXCL9 • STAT1 • TREM2

APX005M in Combination With Systemic Pembrolizumab in Patients With Metastatic Melanoma (clinicaltrials.gov) - P1/2 | N=34 | Terminated | Sponsor: M.D. Anderson Cancer Center | Active, not recruiting ➔ Terminated; <75% participant accrual

Trial termination • Melanoma • Mucosal Melanoma • Oncology • Solid Tumor

A Study of APX005M in Combination With Nivolumab and Ipilimumab in Treatment Naïve Patients With Advanced Melanoma or Renal Cell Carcinoma (RCC) (clinicaltrials.gov) - P1 | N=26 | Active, not recruiting | Sponsor: Yale University | Trial completion date: Feb 2026 ➔ Aug 2026 | Trial primary completion date: Aug 2025 ➔ Feb 2026

Trial completion date • Trial primary completion date • Genito-urinary Cancer • Melanoma • Oncology • Renal Cell Carcinoma • Solid Tumor

INNATE: Immunotherapy During Neoadjuvant Therapy for Rectal Cancer (clinicaltrials.gov) - P2 | N=58 | Active, not recruiting | Sponsor: University of Texas Southwestern Medical Center | Trial completion date: Sep 2025 ➔ Dec 2025 | Trial primary completion date: Sep 2025 ➔ Dec 2025

Trial completion date • Trial primary completion date • Colorectal Adenocarcinoma • Colorectal Cancer • Oncology • Rectal Adenocarcinoma • Rectal Cancer • Solid Tumor

SHR-2005, an FcγR-Dependent CD40 Agonistic Antibody with Potent Antitumor Activities and Favorable Safety Profile. (PubMed, Mol Cancer Ther) - "Notably, SHR-2005 induced significantly lower IL-6 secretion than the APX005M analogue in human peripheral blood mononuclear cells, indicating a favorable safety profile. In conclusion, the CD40 agonistic antibody SHR-2005 was highly reliant on FcγR for agonistic activation and exhibited promising potential for clinical development as monotherapy or in combination with the anti-PD-L1 antibody for the treatment of solid tumors. Based on promising efficacy and tolerance in preclinical studies, SHR-2005 is currently being evaluated in an ongoing phase I clinical trial for the intravesical treatment of high-risk non-muscle-invasive bladder cancer."

Journal • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor • CD40 • CD40LG • IL6

Phase I Study of APX005M in Pediatric Central Nervous System Tumors (clinicaltrials.gov) - P1 | N=32 | Active, not recruiting | Sponsor: Pediatric Brain Tumor Consortium | Trial completion date: Jun 2025 ➔ Sep 2025

Trial completion date • Astrocytoma • Brain Cancer • CNS Tumor • Diffuse Intrinsic Pontine Glioma • Ependymoma • Germ Cell Tumors • Glioblastoma • Glioma • Medulloblastoma • Oncology • Pediatrics • Solid Tumor • CD4 • TMB