A Phase Ib/II Clinical Study on AK112 Combined or Not Combined With AK119 in pMMR/MSS Colorectal Cancer

NCT05846867 | Active Not Recruiting Phase 1

• 1 other identifier: AK119-202
• Study Type: interventional
• Target: 170
• Locations: 1 country
• Sites: 1

Brief Summary

This is an open label, multicenter Phase Ib/II clinical study on the efficacy and safety of AK119 and AK112 in combination with or without chemotherapy, and AK112 monotherapy in pMMR/MSS CRC

Conditions

Colorectal Cancer

Outcome Measures

Primary Outcomes (3)

• Objective response rate (ORR)

  ORR is defined as the proportion of subjects with confirmed CR or confirmed PR

  Up to 2 years

• Number of subjects with adverse events (AEs)

  AE refers to any untoward medical occurrence or deterioration of existing medical event after the subject signed the ICF, whether or not considered related to the study treatment.

  From the time of informed consent signed through 90 days after the last dose of study drug

• recommended phaseII dose

  Phase II clinical study recommended dose (RP2D) of AK119 and AK112 combined with or without chemotherapy

  1 year

Secondary Outcomes (8)

• Progression-free survival (PFS)

  Up to 2 years

• Disease control rate (DCR)

  Up to 2 years

• Duration of response (DoR)

  Up to 2 years

• Time to response (TTR)

  Up to 2 years

• Total survival time (OS) and 12-month OS rate

  Up to 2 years

Study Arms (5)

AK119 20mg/kg+ AK112 20mg/kg

EXPERIMENTAL

Subjects will receive AK119 plus AK112 via intravenously (IV) Q2W, up to 2 years

Drug: AK119; Drug: AK112

AK119 40mg/kg+ AK112 20mg/kg

EXPERIMENTAL

Subjects will receive AK119 plus AK112 via intravenously (IV) Q2W, up to 2 years

Drug: AK119; Drug: AK112

AK119 + AK112 20mg/kg +mFOLFOX6

EXPERIMENTAL

Subjects will receive AK119 and AK112 plus mFOLFOX6 via intravenously (IV)Q2W, up to 12 cycles. Afterward, AK119 and AK112 will continue to be treated up to 2 years.

Drug: AK119; Drug: AK112; Drug: Oxaliplatin; Drug: Calcium folinate; Drug: Fluorouracil

AK119 + AK112 20mg/kg +FOLFIRI

EXPERIMENTAL

Subjects will receive AK119 and AK112 plus FOLFIRI via intravenously (IV)Q2W, up to 12 cycles. Afterward, AK119 and AK112 will continue to be treated up to 2 years.

Drug: AK119; Drug: AK112; Drug: Irinotecan; Drug: Calcium folinate; Drug: Fluorouracil

AK112 20mg/kg

EXPERIMENTAL

Subjects will receive AK112 via intravenously (IV) Q2W, up to 2 years

Drug: AK112

Interventions

AK119 DRUG

AK119 IV every 2 weeks.intravenous infusion

AK119 + AK112 20mg/kg +FOLFIRI; AK119 + AK112 20mg/kg +mFOLFOX6; AK119 20mg/kg+ AK112 20mg/kg; AK119 40mg/kg+ AK112 20mg/kg

AK112 DRUG

AK112 IV every 2 weeks.intravenous infusion

AK112 20mg/kg; AK119 + AK112 20mg/kg +FOLFIRI; AK119 + AK112 20mg/kg +mFOLFOX6; AK119 20mg/kg+ AK112 20mg/kg; AK119 40mg/kg+ AK112 20mg/kg

Irinotecan DRUG

Irinotecan 180mg/m2, intravenous infusion

AK119 + AK112 20mg/kg +FOLFIRI

Calcium folinate DRUG

Calcium folinate: 400mg/m2, intravenous infusion

AK119 + AK112 20mg/kg +FOLFIRI; AK119 + AK112 20mg/kg +mFOLFOX6

Fluorouracil DRUG

Fluorouracil 400mg/m2, intravenous injection

AK119 + AK112 20mg/kg +FOLFIRI; AK119 + AK112 20mg/kg +mFOLFOX6

Oxaliplatin DRUG

Oxaliplatin: 85mg/m2, intravenous infusion

AK119 + AK112 20mg/kg +mFOLFOX6

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Be able to understand and voluntarily sign the written informed consent, which must be signed before the specified research procedure required by the research is implemented.
• Age ≥ 18 when signing the informed consent form (ICF), both male and female。
• Microsatellite stable colorectal cancer confirmed by histopathology; Microsatellite stability was defined as the expression of four common MMR proteins (MLH1, MSH2, MSH6 and PMS2) detected by immunohistochemistry, and all four proteins were positive for pMMR. Or PCR method was used to detect sites (BAT25, BAT26, D5S346, D2S123 and D17S250), and the detection results showed that the stability was microsatellite stability or microsatellite low degree instability.
• The first and second cohorts: recurrent or metastatic colorectal cancer that has failed to undergo at least the second-line standard treatment in the past; The chemotherapy of at least one of the treatment lines is the combination chemotherapy of at least two cytotoxic drugs based on platinum or irinotecan; Definition of treatment failure: disease progression occurs during or after treatment. All patients who change the treatment plan due to drug intolerance are not considered as treatment failure; For subjects who have received induction chemotherapy, concurrent radiotherapy and chemotherapy or adjuvant chemotherapy in the past, if relapse/metastasis occurs within 6 months after the last treatment, the original treatment plan is defined as the first-line treatment plan for the subject.
• The third and fourth cohorts: for patients with advanced colorectal cancer who have not undergone systematic treatment, the recurrence time should be at least 6 months from the end of the last treatment for those who have previously received induction chemotherapy, concurrent radiotherapy and chemotherapy or adjuvant/neoadjuvant chemotherapy.
• Agree to provide archived or freshly obtained tumor tissue samples within 2 years before the first administration (preferably newly obtained tumor tissue samples) About 20 unstained FFPE pathological sections (if the sample size is not enough, only 10 unstained FFPE pathological sections can be provided with the approval of medical inspectors FFPE pathological section).
• According to RECIST v1.1 standard, subjects have at least one measurable target lesion; The focus that has received radiotherapy is not selected as the target lesion, unless the radiotherapy focus is the only measurable focus and the progress is determined according to the imaging, it can be considered as the target lesion.
• The Eastern Cancer Cooperation Organization (ECOG) physical state score is 0 or 1.
• The expected survival period is ≥ 3 months.

You may not qualify if:

• Pathological examination confirmed other pathological types, such as squamous cell carcinoma, sarcoma or undifferentiated carcinoma, gastrointestinal stromal tumor, etc.
• Palliative local treatment for non-target lesions within 2 weeks before the first administration; Have received systemic non-specific immunomodulation therapy (such as interleukin, interferon, thymosin, etc.) within 2 weeks before the first administration; Received Chinese herbal medicine or traditional Chinese patent medicines and simple preparations with anti-tumor indications within 2 weeks before the first administration。
• Had been treated with anti-CD73 inhibitors, immune checkpoint inhibitors (such as anti-PD-1 antibody, anti-PD-L1 antibody, anti-CTLA-4 antibody, etc.), immune checkpoint agonists (such as antibodies against ICOS, CD40, CD137, GITR, OX40 targets, etc.), immune cell therapy (such as CAR-T) and other therapies aimed at tumor immune mechanism.
• There is a history of gastrointestinal perforation and fistula within 6 months before the first administration. If the perforation or fistula has been removed or repaired, and the researcher judges that the disease has recovered or alleviated, it can be admitted into the group.
• Active or inactive Inflammatory bowel disease (such as Crohn's disease or ulcerative colitis) previously recorded. Inability to swallow, malabsorption syndrome, or uncontrollable nausea, vomiting, diarrhea or other gastrointestinal diseases that seriously affect the use and absorption of drugs.
• Except for the tumor that the subject had at the time of enrollment, there was active malignant tumor in the previous five years. However, the tumors participating in the study and cured local tumors are excluded, such as skin basal cell carcinoma, skin squamous cell carcinoma, superficial bladder cancer, cervical carcinoma in situ, breast carcinoma in situ, localized prostate cancer, etc.
• At the same time, another interventional clinical study was enrolled.
• Receive the last systemic anti-tumor treatment within 3 weeks before the first administration; Received small molecular TKI treatment within 2 weeks before the first administration

Sponsors & Collaborators

• Akeso: lead

Study Sites (1)

Cancer Hospital Affiliated to Harbin Medical University

Harbin, China

Location

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

Oxaliplatin; Irinotecan; Leucovorin; Fluorouracil

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Camptothecin; Alkaloids; Heterocyclic Compounds; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes; Enzymes and Coenzymes; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring

Study Officials

• Yanqiao Zhang, PhD

  Cancer Hospital Affiliated to Harbin Medical University

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 26, 2023
• First Posted: May 6, 2023
• Study Start: May 8, 2023
• Primary Completion (Estimated): May 8, 2026
• Study Completion (Estimated): August 11, 2026
• Last Updated: March 4, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)