Evidence map›Paper›PMID 38871975›Full record

ArticleNature medicine2024

Botensilimab plus balstilimab in relapsed/refractory microsatellite stable metastatic colorectal cancer: a phase 1 trial.

Andrea J Bullock, Benjamin L Schlechter, Marwan G Fakih, Apostolia M Tsimberidou, Joseph E Grossman, Michael S Gordon, Breelyn A Wilky, Agustin Pimentel, Daruka Mahadevan, Ani S Balmanoukian and 18 more

2 registry-linked trialsAbstract readClinical Trial, Phase I
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature medicine, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 93 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
93citing papers in PubMed, 2 pooled it
–field-weighted citation impact
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.

NCT03860272 phase1active not recruitingnot on this map

A Phase 1 Study of AGEN1181, an Fc-Engineered Anti-CTLA-4 Monoclonal Antibody as Monotherapy and in Combination With AGEN2034 (Balstilimab), an Anti-PD-1 Monoclonal Antibody, in Subjects With Advanced Cancer

TypeinterventionalSponsorAgenus Inc.Ran2019 to 2027Enrolled499ConditionsAdvanced Cancer, Angiosarcoma, Colorectal Cancer Without Liver Metastases, Endometrial CancerArmsBotensilimab, Balstilimab
NCT07550088 phase2recruitingnot on this mapstarted 2026, after this paper: background citation

A Single-Arm, Phase II Study Evaluating Combination Balstilimab Plus Botensilimab With AgenT-797 in Previously Treated Patients With pMMR Metastatic CRC With Liver Metastases

TypeinterventionalSponsorDarren Sigal, MDRan2026 to 2028Enrolled17ConditionsColorectal Cancer MetastaticArmsBalstilimab (BAL), Botensilimab (BOT), agenT-797
3 · Its place in the literature

Who cites it

93 citing papers in PubMed, 2 syntheses or guidelines pooled it.

  1. Pooled it
  2. Pooled it
  3. Trial
  4. Trial
  5. Trial
  6. Trial
  7. Trial
  8. Trial
  9. Trial
  10. Trial
  11. Trial
  12. Trial
  13. Trial
  14. Trial
  15. Trial
  16. Article
  17. Review
  18. Review
  19. Review
  20. Article

33 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

28 authors.

Andrea J Bullock *Beth Israel Deaconess Medical Center, Boston, MA, USA.ORCID http://orcid.org/0000-0001-7143-0225
Benjamin L Schlechter *Dana-Farber Cancer Institute, Boston, MA, USA.ORCID http://orcid.org/0000-0002-1529-3278
Marwan G Fakih *City of Hope Comprehensive Cancer Center, Duarte, CA, USA.ORCID http://orcid.org/0000-0002-6554-5488
Apostolia M Tsimberidou *The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Joseph E GrossmanAgenus, Inc., Lexington, MA, USA.ORCID http://orcid.org/0000-0002-2130-2783
Michael S GordonHonorHealth Research Institute, Scottsdale, AZ, USA.
Breelyn A WilkyUniversity of Colorado Cancer Center, Aurora, CO, USA.
Agustin PimentelSylvester Comprehensive Cancer Center, University of Miami, Miami, FL, USA.
Daruka MahadevanThe University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.
Ani S BalmanoukianThe Angeles Clinic and Research Institute, Los Angeles, CA, USA.
Rachel E SanbornEarle A. Chiles Research Institute, Providence Cancer Institute, Portland, OR, USA.ORCID http://orcid.org/0000-0003-0542-6054
Gary K SchwartzCase Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH, USA.
Ghassan K Abou-AlfaMemorial Sloan Kettering Cancer Center, New York, NY, USA.
Neil H SegalMemorial Sloan Kettering Cancer Center, New York, NY, USA.
Bruno BockornyBeth Israel Deaconess Medical Center, Boston, MA, USA.ORCID http://orcid.org/0000-0002-9162-1560
Justin C MoserHonorHealth Research Institute, Scottsdale, AZ, USA.
Sunil SharmaHonorHealth Research Institute, Scottsdale, AZ, USA.
Jaymin M PatelAgenus, Inc., Lexington, MA, USA.
Wei WuAgenus, Inc., Lexington, MA, USA.
Dhan ChandAgenus, Inc., Lexington, MA, USA.
Katherine RosenthalAgenus, Inc., Lexington, MA, USA.
Gabriel MednickAgenus, Inc., Lexington, MA, USA.
Chloe DelepineAgenus, Inc., Lexington, MA, USA.ORCID http://orcid.org/0000-0002-1856-9583
Tyler J CurielDartmouth Cancer Center, Lebanon, NH, USA.
Justin StebbingAnglia Ruskin University, Cambridge, UK. justin.stebbing@aru.ac.uk.ORCID http://orcid.org/0000-0002-1117-6947
Heinz-Josef LenzUniversity of Southern California Norris Comprehensive Cancer Center, Los Angeles, CA, USA.ORCID http://orcid.org/0000-0003-2178-9568
Steven J O'Day *Agenus, Inc., Lexington, MA, USA.
Anthony B El-Khoueiry *University of Southern California Norris Comprehensive Cancer Center, Los Angeles, CA, USA. elkhouei@med.usc.edu.

Funding

X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Hongbiao Carl Lekaye · 1985 to 2026
$347.4M
Translational Engineering in Cancer (TEC)P30CA023108 · NCI · DARTMOUTH COLLEGE · PI Fred W Kolling IV · 1985 to 2026
$91.3M
NCI NIH HHS P30 CA008748NCI NIH HHS P30 CA023108
6 · The paper itself

Abstract

Microsatellite stable metastatic colorectal cancer (MSS mCRC; mismatch repair proficient) has previously responded poorly to immune checkpoint blockade. Botensilimab (BOT) is an Fc-enhanced multifunctional anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) antibody designed to expand therapy to cold/poorly immunogenic solid tumors, such as MSS mCRC. BOT with or without balstilimab (BAL; anti-PD-1 antibody) is being evaluated in an ongoing expanded phase 1 study. The primary endpoint is safety and tolerability, which was evaluated separately in the dose-escalation portion of the study and in patients with MSS mCRC (using combined dose-escalation/dose-expansion data). Secondary endpoints include investigator-assessed RECIST version 1.1-confirmed objective response rate (ORR), disease control rate (DCR), duration of response (DOR) and progression-free survival (PFS). Here we present outcomes in 148 heavily pre-treated patients with MSS mCRC (six from the dose-escalation cohort; 142 from the dose-expansion cohort) treated with BOT and BAL, 101 of whom were considered response evaluable with at least 6 months of follow-up. Treatment-related adverse events (TRAEs) occurred in 89% of patients with MSS mCRC (131/148), most commonly fatigue (35%, 52/148), diarrhea (32%, 47/148) and pyrexia (24%, 36/148), with no grade 5 TRAEs reported and a 12% discontinuation rate due to a TRAE (18/148; data fully mature). In the response-evaluable population (n = 101), ORR was 17% (17/101; 95% confidence interval (CI), 10-26%), and DCR was 61% (62/101; 95% CI, 51-71%). Median DOR was not reached (NR; 95% CI, 5.7 months-NR), and median PFS was 3.5 months (95% CI, 2.7-4.1 months), at a median follow-up of 10.3 months (range, 0.5-42.6 months; data continuing to mature). The combination of BOT plus BAL demonstrated a manageable safety profile with no new immune-mediated safety signals and encouraging clinical activity with durable responses. ClinicalTrials.gov identifier: NCT03860272 .

Indexed as

Antibodies, Monoclonal, HumanizedColorectal NeoplasmsAdultAgedAged, 80 and overAntineoplastic Combined Chemotherapy ProtocolsFemaleHumansMaleMicrosatellite InstabilityMicrosatellite RepeatsMiddle AgedNeoplasm MetastasisNeoplasm Recurrence, LocalAntibodies, Monoclonal, Humanized

Identifiers

PMID38871975
PMCPMC11405281

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

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.