Evidence map›Paper›PMID 36738333›Full record

ArticleCancer chemotherapy and pharmacology2023

A phase I, first-in-human study of TAK-164, an antibody-drug conjugate, in patients with advanced gastrointestinal cancers expressing guanylyl cyclase C.

Richard Kim, Alexis D Leal, Aparna Parikh, David P Ryan, Shining Wang, Brittany Bahamon, Neeraj Gupta, Aaron Moss, Joanna Pye, Harry Miao and 2 more

Erratum issued Registry-linked trialOpen access · hybridAbstract readClinical Trial, Phase I
PubMed Full text at PMC Publisher
In one paragraph

Article in Cancer chemotherapy and pharmacology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. It is linked to trial NCT03449030 (An Open-Label, Dose Escalation, Phase 1, First-in-Human Study of TAK-164, an Antibody-Drug Conjugate, in Patients With Advanced Gastrointestinal Cancers Expressing Guanylyl Cyclase C), which is not on this map. Cited by 16 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed, 2 pooled it
4.0field-weighted citation impact, top 6% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT03449030 phase1terminatednot on this map

An Open-Label, Dose Escalation, Phase 1, First-in-Human Study of TAK-164, an Antibody-Drug Conjugate, in Patients With Advanced Gastrointestinal Cancers Expressing Guanylyl Cyclase C

TypeinterventionalSponsorMillennium Pharmaceuticals, Inc.Ran2018 to 2020Enrolled31ConditionsGastrointestinal Neoplasms, Esophageal, Stomach, Pancreas, Colon Neoplasms, Malignant Tumors of Digestive Organ, Advanced Gastrointestinal MalignanciesArmsTAK-164, 89Zr-TAK-164
3 · Its place in the literature

Who cites it

16 citing papers in PubMed, 2 syntheses or guidelines pooled it, 14 citations in OpenAlex.

  1. Prevalence of antibody drug conjugated-induced nausea and vomiting (ADCINV) in patients with cancer.Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer · 2026
    Pooled it
  2. Pooled it
  3. Article
  4. Article
  5. Antibody-drug conjugates in gastric cancer: clinical advances and resistance mechanisms.Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association · 2026
    Review
  6. Review
  7. Review
  8. Review
  9. Review
  10. Review
  11. Review
  12. Immunotherapy for precision medicine in colorectal cancer.Expert review of precision medicine and drug development · 2025
    Article
  13. Review
  14. Antibody-drug conjugates in gastric cancer: from molecular landscape to clinical strategies.Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association · 2024
    Review
  15. Antibody drug conjugates: hitting the mark in pancreatic cancer?Journal of experimental & clinical cancer research : CR · 2023
    Review
  16. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

12 authors at 4 institutions in 1 country.

Richard KimDepartment of Gastroenterology Oncology, Moffitt Cancer Center, Vincent A. Stabile Research Building, 12902 USF Magnolia Drive, Tampa, FL, 33612, USA. richard.kim@moffitt.org.ORCID http://orcid.org/0000-0002-8448-844X
Alexis D LealDivision of Medical Oncology, University of Colorado School of Medicine, Aurora, CO, USA.
Aparna ParikhDivision of Hematology and Oncology, Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA, USA.
David P RyanDivision of Hematology and Oncology, Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA, USA.
Shining WangOncology Clinical Science, Takeda Development Center Americas, Inc. (TDCA), Lexington, MA, USA.
Brittany BahamonTranslational Medicine, Takeda Development Center Americas, Inc. (TDCA), Lexington, MA, USA.
Neeraj GuptaQuantitative Clinical Pharmacology, Takeda Development Center Americas, Inc. (TDCA), Lexington, MA, USA.
Aaron MossPharmacology/Toxicology, Audentes Therapeutics, Inc., San Francisco, CA, USA.
Joanna PyeOncology Statistics, Takeda Development Center Americas, Inc. (TDCA), Lexington, MA, USA.
Harry MiaoClinical Development, Takeda Development Center Americas, Inc. (TDCA), Lexington, MA, USA.
Haig InguilizianGlobal Patient Safety and Evaluation, Takeda Development Center Americas, Inc. (TDCA), Lexington, MA, USA.
James M ClearyDepartment of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
Takeda (United States) · USHarvard University · USMoffitt Cancer Center · USUniversity of Colorado Denver · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

purposeGuanylyl cyclase C (GCC) is highly expressed in several gastrointestinal malignancies and preclinical studies suggest that it is a promising target for antibody-based therapeutics. This phase I trial assessed the safety and tolerability of TAK-164, an investigational, anti-GCC antibody-drug conjugate (NCT03449030).

methodsThirty-one patients with GCC-positive, advanced gastrointestinal cancers received intravenous TAK-164 on day 1 of 21-day cycles. Dose escalation proceeded based on cycle 1 safety data via a Bayesian model.

resultsMedian age was 58 years (range 32-72), 25 patients (80.6%) had colorectal carcinoma, and median number of prior therapies was four. No dose-limiting toxicities (DLTs) were reported during cycle 1 DLT evaluation period. After cycle 2 dosing, 3 patients reported dose-limiting treatment-emergent adverse events (TEAEs): grade 3 pyrexia and grade 5 hepatic failure (0.19 mg/kg), grade 4 hepatic failure and platelet count decreased (0.25 mg/kg), grade 3 nausea, grade 4 platelet and neutrophil count decreased (0.25 mg/kg). The recommended phase II dose (RP2D) was 0.064 mg/kg. Common TAK-164-related TEAEs included platelet count decreased (58.1%), fatigue (38.7%), and anemia (32.3%). There was a dose-dependent increase in TAK-164 exposure over the range, 0.032-0.25 mg/kg. TAK-164 half-life ranged from 63.5 to 159 h. One patient (0.008 mg/kg) with high baseline GCC expression had an unconfirmed partial response.

conclusionsTAK-164 appeared to have a manageable safety profile at 0.064 mg/kg. Hepatic toxicity was identified as a potential risk. The RP2D of 0.064 mg/kg was considered insufficient to derive clinical benefit; there are no plans for further clinical development. CLINICAL

trial registrationNCT03449030.

Indexed as

Antineoplastic AgentsGastrointestinal NeoplasmsImmunoconjugatesAdultAgedAntibodiesBayes TheoremDose-Response Relationship, DrugHumansMaximum Tolerated DoseMiddle AgedReceptors, EnterotoxinAntibodiesAntineoplastic AgentsImmunoconjugatesReceptors, EnterotoxinBiological agents and therapiesClinical-stage researchClinical trial resultsDrug targetsGastrointestinal cancers

Identifiers

PMID36738333
PMCPMC10068631
OpenAlexW4319163937

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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.