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

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

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

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

Personalized Peptide Vaccine in Treating Patients With Advanced Pancreatic Cancer or Colorectal Cancer (clinicaltrials.gov) - P1 | N=150 | Enrolling by invitation | Sponsor: M.D. Anderson Cancer Center | Recruiting ➔ Enrolling by invitation | Trial completion date: May 2025 ➔ May 2027 | Trial primary completion date: May 2025 ➔ May 2027

Enrollment status • Trial completion date • Trial primary completion date • Colorectal Adenocarcinoma • Colorectal Cancer • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • CA 19-9 • CEACAM5

APX005M and Doxorubicin in Advanced Sarcoma (clinicaltrials.gov) - P2 | N=27 | Active, not recruiting | Sponsor: Alexander Z. Wei, MD | Trial completion date: Dec 2025 ➔ Dec 2026 | Trial primary completion date: Dec 2024 ➔ Dec 2026

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

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: Sep 2024 ➔ Jun 2025

IO biomarker • Trial completion date • Tumor mutational burden • Astrocytoma • Brain Cancer • CNS Tumor • Diffuse Intrinsic Pontine Glioma • Ependymoma • Germ Cell Tumors • Glioblastoma • Glioma • Medulloblastoma • Oncology • Pediatrics • Solid Tumor • CD4 • CXCL8 • TMB • TNFA

Clinical outcomes of immunotherapy in metastatic pancreatic carcinoma: A systematic review and meta-analysis. (ASCO-GI 2025) - "Immunotherapies included were GVAX, tremelimumab, Mesothelin-specific Chimeric Antigen Receptor T cells, durvalumab, pembrolizumab, canerpaturev, Sotigalimab, nivolumab, CO-1.01, allogeneic natural killer cell immunotherapy, Anti-EGFR chimeric antigen receptor-modified T cells, bispecific antibody armed T cells, and clivatuzumab tetraxetan... This meta-analysis demonstrates that novel immunotherapies have promising results on metastatic pancreatic cancer. Future new clinical trials with a follow-up on current early-phase results are needed."

Clinical data • Metastases • Retrospective data • Review • Gastrointestinal Cancer • Oncology • Pancreatic Cancer • Solid Tumor • MSLN

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 2025 ➔ Feb 2026 | Trial primary completion date: Aug 2024 ➔ Aug 2025

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

A Phase 2 Study of Sotigalimab, a CD40 Agonist Antibody, Plus Concurrent Chemoradiation as Neoadjuvant Therapy for Esophageal and Gastroesophageal Junction Cancers (Cancer Res Commun) - P2 | N=34 | NCT03165994 | Sponsor: Apexigen America, Inc. | "33 patients were enrolled (AC 76%, SCC 24%; clinical stage III 67%). Ninety percent of patients received all planned doses of sotigalimab. The most common adverse events attributed to sotigalimab were nausea, fever/chills, fatigue, and cytokine release syndrome (CRS); most of these were Grade 1-2. Grade >3 CRS was observed in 3 pts (9%). Twenty-five of the 29 efficacy-evaluable patients underwent an R0 resection (87.9%), with an overall path CR rate of 37.9% (11/29)."

P2 data • Esophageal Cancer • Gastroesophageal Junction Adenocarcinoma

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

Design of a humanized CD40 agonist antibody with specific properties using AlphaFold2 and development of an anti-PD-L1/CD40 bispecific antibody for cancer immunotherapy. (PubMed, Transl Oncol) - "Due to the unique epitope, it demonstrates superior activation compared to APX005M (S267E)...Furthermore, in humanized transgenic mice challenged with huPD-L1-expressing tumor cells, BA4415 induced superior anti-tumor activity. This novel anti-PD-L1/CD40 bispecific antibody holds potential for strong anti-tumor therapeutic efficacy by selectively restricting CD40 stimulation in tumors."

Journal • Oncology • CD40

Sotigalimab May Be a Safe and Feasible Addition to the Rectal Cancer Chemoradiotherapy Paradigm (OncLive) - P2 | N=58 | INNATE (NCT04130854) | "In the sotigalimab arm, 22.2% of patients had a pathological complete response (pCR) or resection vs 14.3% in the control arm, and 36.8% had a major response vs 60%, respectively...Regarding safety, grade 3/4 adverse events (AEs) occurred in 26% of patients on the sotigalimab arm vs 45% in the control arm; 1 toxicity-related reaction was related or possibly related to sotigalimab vs 2 that were related to radiation therapy."

P2 data • Oncology • Rectal Cancer

Clinical and biomarker analyses of intratumoral CD40 agonist sotigalimab in combination with pembrolizumab in metastatic melanoma: A phase I/II trial (ESMO 2024) - P1/2 | "This combination therapy is well tolerated, has a notable clinical response, and generated robust innate and adaptive immunologic response that extended beyond the injected tumors."

Biomarker • Clinical • Combination therapy • IO biomarker • Metastases • P1/2 data • Melanoma • Oncology • Solid Tumor • 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

APX005M With Nivolumab and Cabiralizumab in Advanced Melanoma, Non-small Cell Lung Cancer or Renal Cell Carcinoma (clinicaltrials.gov) - P1 | N=42 | Completed | Sponsor: Yale University | Active, not recruiting ➔ Completed | Trial completion date: Oct 2027 ➔ May 2024

Combination therapy • IO biomarker • Metastases • Trial completion • Trial completion date • Genito-urinary Cancer • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • BRAF • CD163 • CD40LG • CD8 • IFNG • IL10 • PD-L1

Phase 1 study of the CD40 agonistic monoclonal antibody APX005M (sotigalimab) in pediatric, adolescent, and young adult patients with recurrent or progressive CNS tumors and newly diagnosed brain stem glioma: a Pediatric Brain Tumor Consortium study (PBTC-051; NCT03389802) (ISPNO 2024) - P1 | "APX005M was well-tolerated in pediatric patients with both recurrent/refractory/progressive CNS tumors and post-radiation pre-progression DIPG. A RP2D was established for both populations. Future studies of this agent in pediatric neuro-oncology patients should prioritize combination therapy."

Clinical • P1 data • Biliary Tract Cancer • Brain Cancer • CNS Tumor • Diffuse Intrinsic Pontine Glioma • Ependymoma • Glioma • Hematological Disorders • Leukopenia • Neutropenia • Oncology • Pediatrics • Solid Tumor • CD40

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 | Recruiting ➔ Active, not recruiting

Combination therapy • Enrollment closed • Metastases • Genito-urinary Cancer • Melanoma • Oncology • Renal Cell Carcinoma • Solid Tumor

Phase I Study of APX005M in Pediatric CNS Tumors (clinicaltrials.gov) - P1 | N=32 | Active, not recruiting | Sponsor: Pediatric Brain Tumor Consortium | Trial completion date: Mar 2024 ➔ Sep 2024

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

Tissue assessment of therapeutic responses to neoadjuvant short course radiotherapy with and without anti-CD40 immunotherapy sotigalimab (sotiga) in rectal cancer. (ASCO-GI 2023) - P2 | "On treatment biopsies during neoadjuvant therapy for rectal cancer enables deep assessment of therapeutic response, provides insight into action of investigational agents, and may identify therapy specific predictive biomarkers. Our data shows that SCRT can induce immune responses and adaptive immune responses can be further induced by sotiga."

Clinical • IO biomarker • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Rectal Cancer • Solid Tumor

APX005M in Combination With Systemic Pembrolizumab in Patients With Metastatic Melanoma (clinicaltrials.gov) - P1/2 | N=32 | Active, not recruiting | Sponsor: M.D. Anderson Cancer Center | Trial completion date: Apr 2024 ➔ Apr 2025 | Trial primary completion date: Apr 2024 ➔ Apr 2025

Combination therapy • Metastases • Trial completion date • Trial primary completion date • Melanoma • Mucosal Melanoma • Oncology • Solid Tumor

APX005M and Doxorubicin in Advanced Sarcoma (clinicaltrials.gov) - P2 | N=27 | Active, not recruiting | Sponsor: Alexander Z. Wei, MD | Recruiting ➔ Active, not recruiting

Enrollment closed • Oncology • Sarcoma • Soft Tissue Sarcoma • Solid Tumor • CD40

Neoadjuvant CD40 agonism remodels the tumor immune microenvironment in locally advanced esophageal/gastroesophageal junction cancer. (PubMed, Cancer Res Commun) - "These findings indicate that a single dose of sotigalimab leads to enhanced antigen presentation that can activate T cells and induce new T cell clones. This restructuring of the TME provides elements which are critical to the development of effective antitumor immune responses and improved clinical outcomes."

IO biomarker • Journal • Metastases • Esophageal Cancer • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • Oncology • Solid Tumor • CD40