Reference Detail

Contact

Missing content? – Request curation!

Request curation for specific Genes, variants, or PubMed publications.

Have questions, comments or suggestions? - Let us know!

Email us at : ckbsupport@jax.org

Ref Type
PMID
Authors Laura Quan Man Chow, Justin F. Gainor, Nehal J. Lakhani, Hyun Cheol Chung, Keun-Wook Lee, Jeeyun Lee, Patricia LoRusso, Yung-Jue Bang, F. Stephen Hodi, Philip Fanning, Yonggang Zhao, Feng Jin, Hong Wan, Jaume Pons, Sophia Randolph, Wells A. Messersmith
Title A phase I study of ALX148, a CD47 blocker, in combination with established anticancer antibodies in patients with advanced malignancy.
Journal Journal of Clinical Oncology
Vol 37
Issue 15_suppl
Date
URL https://ascopubs.org/doi/abs/10.1200/JCO.2019.37.15_suppl.2514
Abstract Text Background: CD47 is a myeloid checkpoint upregulated by tumor cells to evade the host’s immune response. ALX148 (A) is a fusion protein comprised of a high affinity CD47 blocker linked to an inactive human immunoglobulin Fc region. ALX148 is well tolerated in combination with pembrolizumab (P) or trastuzumab (T) with no maximum tolerated dose (MTD) identified (ASCO 2018 #3068, SITC 2018 #P335). Safety and antitumor activity of ALX148 (10 mg/kg QW) in combination with T or P are reported in patients (pts) including those with anti-HER2 or checkpoint inhibitor (CPI) relapsed/refractory diseases. Methods: Patients with malignancy including non-small cell lung cancer (NSCLC: CPI resistant/refractory or PD-L1 tumor proportion score <50%) and head and neck squamous cell carcinoma (HNSCC: progressed on platinum therapy) received A+P. Patients with HER2 malignancy including gastric/gastroesophageal junction (GEJ) cancer (progressed on T + fluoropyrimidine-based therapy) received A+T. Safety, response, pharmacokinetic (PK), and pharmacodynamic (PD) markers were assessed. Preliminary data from fully enrolled cohorts are reported as of 20 Jan 2019 (safety)/28 Jan 2019 (efficacy). Results: Seventy-nine pts received A+P (All, n=50; NSCLC, n=23; HNSCC, n=20) or A+T (All, n=29; Gastric/GEJ, n=23) as of data cutoff. Forty-seven pts reported mostly low grade treatment related adverse events. The most common were fatigue (11%), AST increase (9%), ALT increase (8%), anemia (8%), and platelets decreased (6%). In select tumor histologies, anticancer activity was observed in initial response-evaluable pts [NSCLC (n=23) 1PR, 8SD; HNSCC (n=17) 3PR, 4SD; and Gastric/GEJ (n=21) 4PR, 6SD]. Preliminary results indicate favorable ALX148 PK and CD47 target occupancy profiles, and positive effects on tumor infiltrating immune cells. Results will be updated at presentation. Conclusions: ALX148 demonstrates excellent tolerability with favorable PK/PD characteristics to date. Objective responses were observed in patients with late line NSCLC, HNSCC, and Gastric/GEJ, including disease relapsed/refractory to prior CPI and HER2-targeted therapies. Clinical trial information: NCT03013218.

Filtering

  • Case insensitive filtering will display rows where any text in any cell matches the filter term
  • Simple literal full or partial string matches
  • Separate multiple filter terms with a spaces, order doesn't matter (a b c and c b a are equivalent )
  • Filtering will only apply to rows that are already loaded on the page, filtering has no impact on query parameters
  • Use quotes to match a longer phrase which contains spaces "mtor c1483f"

Sorting

  • Generally, the default sort order for tables is set to be first column ascending, however, specific tables may set a different default sort order.
  • Click on any column header arrows to sort by that column
  • Hold down the Shift key and click multiple columns to sort by more than one column, be sure to set ascending or descending order for a given column, before moving on to the next column.

Molecular Profile Treatment Approach
Gene Name Source Synonyms Protein Domains Gene Description Gene Role
Therapy Name Drugs Efficacy Evidence Clinical Trials
Drug Name Trade Name Synonyms Drug Classes Drug Description
Gene Variant Impact Protein Effect Variant Description Associated with drug Resistance
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
Unknown unknown stomach cancer not applicable ALX148 + Trastuzumab Phase I Actionable In a Phase I trial, ALX148 and Herceptin (trastuzumab) combination treatment resulted in a partial response in 19% (4/21) and stable disease in 29% (6/21) of patients with gastric or gastroesophageal junction cancer that progressed on chemotherapy (J Clin Oncol 37, no. 15_suppl (May 20, 2019) 2514-2514; NCT03013218). detail...
Unknown unknown gastroesophageal junction adenocarcinoma not applicable ALX148 + Trastuzumab Phase I Actionable In a Phase I trial, ALX148 and Herceptin (trastuzumab) combination treatment resulted in a partial response in 19% (4/21) and stable disease in 29% (6/21) of patients with gastric or gastroesophageal junction cancer that progressed on chemotherapy (J Clin Oncol 37, no. 15_suppl (May 20, 2019) 2514-2514; NCT03013218). detail...
Unknown unknown lung non-small cell carcinoma not applicable ALX148 + Pembrolizumab Phase I Actionable In a Phase I trial, ALX148 and Keytruda (pembrolizumab) combination treatment resulted in a partial response in 4% (1/23) and stable disease in 35% (8/23) of patients with non-small cell lung cancer resistant or refractory to immune checkpoint inhibitors (J Clin Oncol 37, no. 15_suppl (May 20, 2019) 2514-2514; NCT03013218). detail...
Unknown unknown head and neck squamous cell carcinoma not applicable ALX148 + Pembrolizumab Phase I Actionable In a Phase I trial, ALX148 and Keytruda (pembrolizumab) combination treatment resulted in a partial response in 18% (3/17) and stable disease in 24% (4/17) of patients with head and neck squamous cell carcinoma that progressed on platinum therapy (J Clin Oncol 37, no. 15_suppl (May 20, 2019) 2514-2514; NCT03013218). detail...