GB1275 / Gossamer Bio - LARVOL DELTA

Context-dependent activation of STING-interferon signaling by CD11b agonists enhances anti-tumor immunity. (PubMed, Cancer Cell) - "Using tissues from phase I clinical studies, we demonstrate that GB1275 treatment activates STING and STAT1 signaling in TAMs in human tumors. These findings suggest potential mechanism-based therapeutic strategies for CD11b agonists and identify patient populations more likely to benefit."

Journal • Gastrointestinal Cancer • Hepatology • Metabolic Disorders • Oncology • Pancreatic Cancer • Solid Tumor • ITGAM • NF-κβ • STING

[VIRTUAL] Combining transcriptomic- and tissue-based immune biomarkers to evaluate GB1275, a CD11b modulator, as a single agent or with pembrolizumab in patients with advanced solid tumors (SITC 2020) - P1/2 | "Ethics Approval This ongoing study is being conducted in accordance with the the Declaration of Helsinki and Council for International Organizations of Medical Sciences (CIOMS) International Ethical Guidelines. The study was approved by the Ethics Boards of University of Colorado Hospital, Washington University School of Medicine - Siteman Cancer Center, Memorial Sloan Kettering Cancer Center, The Sarah Cannon Research Institute/Tennessee Oncology, South Texas Accelerated Research Therapeutics, and The Royal Marsden NHS Foundation Trust."

Biomarker • Clinical • Oncology • Solid Tumor • CD8 • ITGAM

[VIRTUAL] Preliminary results from KEYNOTE-A36, a study of GB1275, a first-in-class oral CD11b modulator, alone and with pembrolizumab or chemotherapy in specified advanced solid tumors (SITC 2020) - P1/2 | "In phase 1, cohorts of 3 to 6 patients with histologically confirmed, locally advanced/metastatic pancreatic, esophageal, gastric, MSS colorectal, metastatic castrate-resistant prostate cancer, or triple negative breast cancer are sequentially assigned to one of the ascending dose levels of GB1275 orally twice daily (BID) in 1 of 3 regimens: A (GB1275 monotherapy); B (GB1275 + pembrolizumab) commenced after completion of two cohorts of A; and C (GB1275 + nab-paclitaxel + gemcitabine) will be initiated after A. Patients in Regimens A and B had previously exhausted standard of care treatment options. Ethics Approval This ongoing study is being conducted in accordance with the Declaration of Helsinki and Council for International Organizations of Medical Sciences (CIOMS) International Ethical Guidelines. The study was approved by the Ethics Boards of the University of Colorado Hospital, Washington University School of Medicine - Siteman Cancer Center, Memorial Sloan..."

IO biomarker • Breast Cancer • Genito-urinary Cancer • Oncology • Pancreatic Cancer • Prostate Cancer • Solid Tumor • Triple Negative Breast Cancer • CD8 • ITGAM

EOSINOPHILIC PNEUMONIA SECONDARY TO IMMUNE CHECKPOINT INHIBITOR THERAPY WITH PEMBROLIZUMAB (CHEST 2022) - "Medications included pembrolizumab and study drug GB1275-1101, an investigative anti-CD11/CD18 therapy...Nivolumab monotherapy is the most frequent culprit, followed by pembrolizumab... Eosinophilic pneumonia is a rare complication of ICI therapy. We recommend monitoring AECs regularly in patients receiving ICIs and considering a diagnosis of eosinophilic pneumonia in those that develop pulmonary infiltrates."

Checkpoint inhibition • Cough • Eosinophilia • Esophageal Cancer • Fatigue • Gastric Adenocarcinoma • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • Human Immunodeficiency Virus • Immune Modulation • Infectious Disease • Inflammation • Oncology • Pneumonia • Respiratory Diseases • Solid Tumor • ITGB2

KEYNOTE-A36: GB1275 Monotherapy and in Combination With an Anti-PD1 Antibody in Patients With Specified Advanced Solid Tumors or in Combination With Standard of Care in Patients With Metastatic Pancreatic Adenocarcinoma (clinicaltrials.gov) - P1/2 | N=61 | Terminated | Sponsor: GB006, Inc., a wholly owned subsidiary of Gossamer Bio, Inc. | N=242 ➔ 61 | Trial completion date: Mar 2023 ➔ Apr 2022 | Active, not recruiting ➔ Terminated | Trial primary completion date: Mar 2023 ➔ Apr 2022; No clear benefit of GB1275 was observed either as monotherapy or in combination with pembrolizumab.

Enrollment change • Trial completion date • Trial primary completion date • Trial termination • Breast Cancer • Colorectal Adenocarcinoma • Colorectal Cancer • Esophageal Adenocarcinoma • Esophageal Cancer • Esophageal Squamous Cell Carcinoma • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • Genito-urinary Cancer • Head and Neck Cancer • Hepatocellular Cancer • Hepatology • Lung Cancer • Neuroendocrine Tumor • Non Small Cell Lung Cancer • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Prostate Cancer • Renal Cell Carcinoma • Small Cell Lung Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Triple Negative Breast Cancer • Urothelial Cancer • PD-L1

KEYNOTE-A36: GB1275 Monotherapy and in Combination With an Anti-PD1 Antibody in Patients With Specified Advanced Solid Tumors or in Combination With Standard of Care in Patients With Metastatic Pancreatic Adenocarcinoma (clinicaltrials.gov) - P1/2; N=242; Active, not recruiting; Sponsor: GB006, Inc., a wholly owned subsidiary of Gossamer Bio, Inc.; Recruiting ➔ Active, not recruiting

Clinical • Combination therapy • Enrollment closed • Monotherapy • Breast Cancer • Colorectal Adenocarcinoma • Colorectal Cancer • Esophageal Adenocarcinoma • Esophageal Cancer • Esophageal Squamous Cell Carcinoma • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • Genito-urinary Cancer • Head and Neck Cancer • Hepatocellular Cancer • Hepatology • Lung Cancer • Neuroendocrine Tumor • Non Small Cell Lung Cancer • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Prostate Cancer • Renal Cell Carcinoma • Small Cell Lung Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Triple Negative Breast Cancer • Urothelial Cancer • PD-L1

Correction: GB1275, a first-in-class CD11b modulator: rationale for immunotherapeutic combinations in solid tumors. (PubMed, J Immunother Cancer) - No abstract available

Journal • Oncology • Solid Tumor • ITGAM

[VIRTUAL] A phase I/II study of GB1275, a first-in-class oral CD11b modulator, alone, and combined with pembrolizumab in specified advanced solid tumors or with chemotherapy in metastatic pancreatic cancer (KEYNOTE-A36). (ASCO 2020) - P1/2 | "This ongoing first-in-human study consists of dose escalation of GB1275 monotherapy (Regimen A), GB1275 + pembrolizumab (Regimen B), and GB1275 + nab-paclitaxel + gemcitabine (Regimen C), followed by Phase 2 expansion in newly diagnosed metastatic pancreatic, MSS colorectal, and PD-L1-positive gastric/GEJ cancers... Preliminary data show minimal treatment-related toxicities with the studied regimens. PK data support BID dosing. Dose escalation is ongoing."

IO Biomarker • P1/2 data • Breast Cancer • Gastrointestinal Cancer • Immune Modulation • Inflammation • Oncology • Pancreatic Cancer • Solid Tumor • CD8 • ITGAM • PD-L1

[VIRTUAL] Preliminary results from KEYNOTE-A36, a study of GB1275, a first-in-class oral CD11b modulator, alone and with pembrolizumab or chemotherapy in specified advanced solid tumors (SITC 2020) - P1/2 | "In phase 1, cohorts of 3 to 6 patients with histologically confirmed, locally advanced/metastatic pancreatic, esophageal, gastric, MSS colorectal, metastatic castrate-resistant prostate cancer, or triple negative breast cancer are sequentially assigned to one of the ascending dose levels of GB1275 orally twice daily (BID) in 1 of 3 regimens: A (GB1275 monotherapy); B (GB1275 + pembrolizumab) commenced after completion of two cohorts of A; and C (GB1275 + nab-paclitaxel + gemcitabine) will be initiated after A. Patients in Regimens A and B had previously exhausted standard of care treatment options. Ethics Approval This ongoing study is being conducted in accordance with the Declaration of Helsinki and Council for International Organizations of Medical Sciences (CIOMS) International Ethical Guidelines. The study was approved by the Ethics Boards of the University of Colorado Hospital, Washington University School of Medicine - Siteman Cancer Center, Memorial Sloan..."

IO biomarker • Breast Cancer • Genito-urinary Cancer • Oncology • Pancreatic Cancer • Prostate Cancer • Solid Tumor • Triple Negative Breast Cancer • CD8 • ITGAM

A phase 1/2 study of GB1275, a novel CD11b modulator, as monotherapy and with an anti-PD-1 antibody in specified advanced solid tumors or with chemotherapy in metastatic pancreatic cancer (mPDAC) (SITC 2019) - " This is an open-label, first-in-human study consisting of a Phase 1 Dose Escalation phase with Regimen A using GB1275 monotherapy and Regimen B using GB1275 with an anti-PD-1 antibody in pts with pancreatic, esophageal, gastric/GEJ, triple negative breast, castration resistant prostate, or Microsatellite Stable Colorectal Cancer (MSS CRC) and Regimen C (GB1275 with Nab-paclitaxel + Gemcitabine (Nab-P+Gem)) in mPDAC, followed by a Phase 2 Expansion phase with three cohorts planned: newly diagnosed stage IV mPDAC, MSS CRC and PD-L1+ gastric/GEJ cancer. N/A"

Monotherapy • P1/2 data

[VIRTUAL] Combining transcriptomic- and tissue-based immune biomarkers to evaluate GB1275, a CD11b modulator, as a single agent or with pembrolizumab in patients with advanced solid tumors (SITC 2020) - P1/2 | "Ethics Approval This ongoing study is being conducted in accordance with the the Declaration of Helsinki and Council for International Organizations of Medical Sciences (CIOMS) International Ethical Guidelines. The study was approved by the Ethics Boards of University of Colorado Hospital, Washington University School of Medicine - Siteman Cancer Center, Memorial Sloan Kettering Cancer Center, The Sarah Cannon Research Institute/Tennessee Oncology, South Texas Accelerated Research Therapeutics, and The Royal Marsden NHS Foundation Trust."

Biomarker • Clinical • Oncology • Solid Tumor • CD8 • ITGAM

[VIRTUAL] A phase 1/2 study of GB1275, a first-in-class CD11b modulator, as monotherapy and with an anti-PD-1 antibody in specified advanced solid tumors or with chemotherapy in metastatic pancreatic cancer (KEYNOTE-A36) (AACR-I 2020) - P1/2 | " This is an open-label, first-in-human study comprising phase 1 dose escalation of GB1275 monotherapy (Regimen A) and GB1275 plus pembrolizumab (Regimen B) in patients with previously treated, locally advanced or metastatic PDA, esophageal, gastric/GEJ, triple negative breast, castration-resistant prostate, or microsatellite-stable colorectal cancer (MSS CRC), and GB1275 plus nab-paclitaxel and gemcitabine (Nab-P+Gem) (Regimen C) in mPDAC. Adverse events are graded per CTCAE v5.0, responses per RECIST v1.1. This study is open for recruitment (NCT04060342)."

Monotherapy • P1/2 data • ITGAM • PD-L1

[VIRTUAL] Preliminary clinical and biologic results of GB1275, a first-in-class oral CD11b modulator, alone and with pembrolizumab, in advanced solid tumors (KEYNOTE A36). (ASCO 2021) - P1/2 | "In Regimen B (800 mg), one partial response was reported in a subject with MSS-CRC treated for 263 days, and one prolonged stable disease (227 days) was reported in a gastric cancer (GC) subject previously treated with pembrolizumab plus bavituximab for less than 3 months due to progression; both subjects are continuing study treatment . Dose escalation of GB1275, up to 1200 mg in Regimens A and B, demonstrated tolerability as monotherapy and combined with pembrolizumab in subjects with advanced cancers . Encouraging antitumor activity in Regimen B (800 mg) was observed in subjects with MSS-CRC and GC . Biological activity reflected by MDSC modulations in blood and TIL Increases in tumor biopsies with GB1275 alone and with pembrolizumab supports the mechanism of GB1275 ."

Clinical • Dermatology • Gastric Cancer • Gastrointestinal Cancer • Oncology • Pruritus • Solid Tumor • CD8 • ITGAM

GB1275, a first-in-class CD11b modulator: rationale for immunotherapeutic combinations in solid tumors. (PubMed, J Immunother Cancer) - P1/2 | "Based on the promising results from preclinical studies, a phase 1/2 clinical study (NCT04060342) of GB1275 in patients with advanced solid tumor types known to be resistant or less likely responsive to immuno-oncology therapies, including pancreatic, breast, prostate, and microsatellite-stable colorectal cancer, is ongoing. In this review, we examine targeting MDSCs as a therapeutic approach in cancer therapy, with a special focus on GB1275 preclinical studies laying the rationale for the phase 1/2 clinical study."

Journal • Breast Cancer • Colorectal Cancer • Gastrointestinal Cancer • Immune Modulation • Inflammation • Lung Cancer • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Solid Tumor • ITGAM

Gossamer Bio Announces Second Quarter 2021 Financial Results and Provides Corporate Update (Businesswire) - "Gossamer will discontinue clinical development of its immuno-oncology product candidate, GB1275, which is currently in a Phase 1/2 clinical trial in solid tumor indications as a monotherapy and in combination with either pembrolizumab or chemotherapy."

Discontinued • Oncology • Solid Tumor

Gossamer Bio Announces First Quarter 2021 Financial Results and Provides Corporate Update (Businesswire) - "Additional clinical data from the ongoing GB1275 Phase 1/2 will be presented at the American Society of Clinical Oncology (ASCO) 2021 Annual Meeting being held virtually from June 4 – 8, 2021."

P1/2 data • Gastric Cancer • Gastrointestinal Cancer • Oncology • Pancreatic Cancer • Solid Tumor

KEYNOTE-A36: GB1275 Monotherapy and in Combination With an Anti-PD1 Antibody in Patients With Specified Advanced Solid Tumors or in Combination With Standard of Care in Patients With Metastatic Pancreatic Adenocarcinoma (clinicaltrials.gov) - P1/2; N=202; Recruiting; Sponsor: GB006, Inc., a wholly owned subsidiary of Gossamer Bio, Inc.

Clinical • Combination therapy • Monotherapy • New P1/2 trial • Breast Cancer • Colorectal Adenocarcinoma • Colorectal Cancer • Esophageal Adenocarcinoma • Esophageal Cancer • Esophageal Squamous Cell Carcinoma • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • Genito-urinary Cancer • Head and Neck Cancer • Hepatocellular Cancer • Hepatology • Lung Cancer • Neuroendocrine Tumor • Non Small Cell Lung Cancer • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Prostate Cancer • Renal Cell Carcinoma • Small Cell Lung Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Thoracic Cancer • Triple Negative Breast Cancer • PD-L1

Gossamer Bio Announces GB1275 Data Presentations at 2020 Society for Immunotherapy of Cancer Annual Meeting (Businesswire) - “Gossamer Bio, Inc…announced that it will present data relevant to GB1275 at the 35th Annual Meeting of the Society for Immunotherapy of Cancer (SITC), to be held virtually from November 9-14, 2020. This includes clinical and biomarker data from the ongoing GB1275 Phase 1/2 clinical trial, KEYNOTE-A36, in advanced solid tumors and corresponding presentations from Johanna Bendell, M.D. and Wells Messersmith, M.D.”

P1/2 data • Oncology • Solid Tumor

Gossamer Bio Announces Third Quarter 2020 Financial Results and Provides Corporate Update (GlobeNewswire) - "Gossamer Bio, Inc…announced its financial results for the third quarter of 2020 and provided a corporate update….Two GB1275 posters are being presented at the 35th Annual Meeting of the Society for Immunotherapy of Cancer (SITC 2020), being held virtually from November 9 - 14. This includes clinical and biomarker data from the ongoing GB1275 Phase 1/2 clinical trial, KEYNOTE-A36, in advanced solid tumors and corresponding presentations from Johanna Bendell, M.D. and Wells Messersmith, M.D."

P1/2 data • Oncology • Solid Tumor

Gossamer Bio Announces Fourth Quarter and Full-Year 2020 Financial Results and Provides Business Update (Businesswire) - "GB1275: Oral CD11b Modulator for Oncology Indications....Enrollment ongoing in a Phase 1 expansion cohort studying the recommended Phase 2 dose in KEYNOTE-A36, a Phase 1/2 clinical trial, including patients with gastric or esophageal cancer who have progressed after initial response to anti-PD-1 therapy and patients with advanced MSS colorectal cancer. Further Phase 1 data expected from this study in 2021."

Enrollment status • P1 data • Colorectal Cancer • Gastrointestinal Cancer • Oncology

Gossamer Bio Announces Second Quarter 2020 Financial Results and Provides Corporate Update (Businesswire) - "Further Phase 1 data from KEYNOTE-A36, a Phase 1/2 study to evaluate GB1275 as a monotherapy and in combination with either KEYTRUDA® (pembrolizumab) or chemotherapy in patients with selected solid tumors, are expected to be announced in the fourth quarter of 2020."

P1/2 data • Oncology • Solid Tumor

Gossamer Bio announces early encouraging safety and biomarker data from phase 1/2 Study of GB1275 at American Society of Clinical Oncology 2020 Virtual Scientific Program (Businesswire) - P1/2, N=202; KEYNOTE-A36 (NCT04060342); Sponsor: GB006, Inc; "The KEYNOTE-A36 Phase 1/2 study is currently undergoing dose escalation of GB1275 as a monotherapy and in combination with KEYTRUDA® (pembrolizumab). As of the March 27, 2020 data cutoff, 22 patients had been enrolled in the study. GB1275 has been well tolerated to date, both as monotherapy and in combination with KEYTRUDA. No dose-limiting toxicities have been reported, and dose escalation in both arms continues....Gossamer expects to present additional data from the KEYNOTE-A36 study in the second half of 2020."

P1/2 data • Trial status • Oncology • Pancreatic Cancer

Positive Allosteric Modulation of CD11b as a Novel Therapeutic Strategy Against Lung Cancer. (PubMed, Front Oncol) - "GB1275 is a novel small molecule modulator of CD11b that is currently in Phase 1/2 clinical development...The profiling also showed a significant decrease in CCL2 levels and a concomitant reduction in Ly6C monocytes in circulation in both groups. These findings suggest that positive allosteric modulation of CD11b reduces TAM density and reprograms them to enhance the adaptive immune response and is a novel therapeutic strategy against lung cancer."

Journal • Lung Cancer • Oncology • Solid Tumor • Thoracic Cancer • CCL2 • CD8 • ITGAM

Gossamer Bio announces fourth quarter and full-year 2019 financial results and provides business update (Businesswire) - “GB1275: Oral CD11b Modulator for Oncology Indications: Enrollment for the KEYNOTE-A36 Phase 1/2 study to evaluate GB1275 as a monotherapy and in combination with either KEYTRUDA® (pembrolizumab) or chemotherapy in patients with selected advanced solid tumors is underway, and we expect to report initial Phase 1 data in the second half of this year.”

Enrollment status • P1 data

GB1275 + Keytruda: Data from P1 portion of P1/2 trial (NCT04060342) for metastatic pancreatic adenocarcinoma in H2 2020 (Gossamer Bio) - Guggenheim Healthcare Talks Neuro/Immunology Day Conference: Data from P2 portion of P1/2 trial for metastatic solid tumors in H2 2021

P1 data • P2 data