KN046 Plus Regorafenib or Apatinib in MSI-H Digestive System Cancers Resistant to PD-1/PD-L1 Blockade

Program Status

Recruiting

Phase

Phase 2

Prior Immunotherapy Allowed

Yes

CRC-directed Trial

Yes

Drugs

apatinib, KN046, Regorafenib

Tags

MSI-H/ MMRd

Comments

Trial only in China, that admits only patients with MSI-H/MMRd cancer (not MSS) that has been resistant to  PD-1/PD-L1 blockade. Then, prior anti PD-1 therapy is required.

Preliminary results for other cancers (non-small cell lung cancer, pancreatic) resistant to PD-1/L1 inhibitor.
Patients receive the combination of 3 agents:

KN046: a PD-L1/CTLA-4 bispecific antibody (blocks both PD-L1 interaction with PD-1 and CTLA-4 interaction with CD80/CD86). Experimental.

Regorafenib: multi-target tyrosine kinase inhibitor, standard third-line therapy in mCRC (Stivarga)

Apatinib: small molecule, selective vascular endothelial growth factor receptor-2 (VEGFR-2) tyrosine kinase inhibitor (TKI).

Location Location Status
China
Peking University Cancer Hospital
Beijing
Recruiting

Contacts

Zhenghang Wang
Contact
01088196561 zhenghang_wang@bjmu.edu.cn
Ting Xu
Contact
18201137836 xtlmhxt@163.com

Inclusion Criteria

Inclusion Criteria:

Subjects are able to comprehend the informed consent form, voluntarily participate, and sign the informed consent form.
Subjects are ≥18 years old on the day of signing the informed consent form, with no gender restrictions.
Histologically confirmed digestive system cancers.
According to RECIST 1.1 criteria, there should be at least one measurable or evaluable lesion at baseline. If the subject has only one measurable or evaluable lesion at baseline, the lesion must not have been exposed to radiotherapy previously, or there must be evidence of significant progression after radiotherapy treatment completion.
ECOG performance status of 0 or 1.
Expected survival ≥3 months.
Archived tumor tissue samples or freshly obtained tumor tissue samples are available.
Female subjects of childbearing potential or male subjects with partners of childbearing potential agree to use highly effective contraception from 7 days before the first dose until 120 days after the last dose. Female subjects of childbearing potential must have a negative serum pregnancy test within 7 days before the first dose.
Subjects have the ability and willingness to comply with the study protocol's visits, treatment plan, laboratory tests, and other study-related procedures.
Within the first 7 days of initial dosing, subjects should have good organ function:
HGB ≥ 80g/L, NEU ≥ 1.0*10^9/L, PLT ≥ 75*10^9/L, Cr≤1.5×ULN or CrCl≥50mL/min(Cockcroft-Gault method), TBiL ≤ 1.5×ULN, ALT and AST ≤3 ×ULN; for patients with liver metastasis ALT and AST ≤5 ×ULN, urine protein <2+;,if urine protein ≥ 2+, 24 hour urinary protein quantity 470 msec , difficult-to-correct hypokalemia, long QT syndrome, atrial fibrillation with resting heart rate >100 bpm, or severe valvular heart disease); g) active bleeding that cannot be controlled after medical treatment.
Toxicity from previous antitumor treatments has not recovered to Grade ≤2 (NCI-CTCAE v5.0) or baseline, except for alopecia, skin pigmentation (allowed at any level), and immune-related adverse reactions requiring physiological replacement (e.g., hypothyroidism, hypopituitarism, type 1 diabetes).
History of allogeneic bone marrow or organ transplantation.
Previous history of allergic reactions, hypersensitivity reactions, or intolerance to antibody drugs (e.g., severe allergic reactions, immune-mediated hepatotoxicity, immune-mediated thrombocytopenia, or anemia).
Pregnant and/or lactating females.
Other conditions that, in the investigator's opinion, may affect the safety or compliance of the study drug treatment, including but not limited to moderate to large pleural/ascites/pericardial effusion, uncorrectable pleural/ascites/pericardial effusion, intestinal obstruction or subacute intestinal obstruction, psychiatric disorders, etc.
Previous treatment with any immune checkpoint inhibitors in combination with anti-VEGF tyrosine kinase inhibitor, including but not limited to Regorafenib, Apatinib, Sulfatinib and Anlctinib.

NCT ID

NCT06099821

Date Trial Added

2023-10-25

Updated Date

2023-10-26