A Study of AK112 With or Without AK117 in Metastatic Colorectal Cancer

NCT05382442 | Active Not Recruiting Phase 2 FDA Drug

• 1 other identifier: AK112-206
• Study Type: interventional
• Target: 254
• Locations: 2 countries
• Sites: 4

Brief Summary

This trial is a Phase II study. The purpose of this study is to evaluate the efficacy, safety, and pharmacokinetics of AK112 with or without AK117 in participants with metastatic colorectal cancer who are not suitable for surgery.

Conditions

Metastatic Colorectal Cancer

Outcome Measures

Primary Outcomes (2)

• Objective response rates (ORR)

  ORR is the proportion of subjects with complete response(CR) or partial response(PR) , based on RECIST v1.1

  Up to approximately 2 years

• Number of participants with adverse events (AEs)

  An AE is any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment.

  Up to approximately 2 years

Secondary Outcomes (6)

• Disease control rate (DCR)

  Up to approximately 2 years

• Duration of response (DOR)

  Up to approximately 2 years

• Time to response (TTR)

  Up to approximately 2 years

• Progression-free survival (PFS)

  Up to approximately 2 years

• Progression-free survival 2 (PFS2)

  Up to approximately 2 years

Study Arms (11)

Part 1_Chemotherapy Regimen Selection Stage Group A(AK112+AK117+XELOX)

EXPERIMENTAL

AK112+AK117+XELOX AK112 and AK117 and XELOX(Oxaliplatin 130 mg/sqm iv day 1, Capecitabine via oral, the total daily dose was 2000mg/sqm, day1-14) If no progression occurs during AK112 plus AK117 plus XELOX, patients will receive maintenance capecitabine plus AK112 plus AK117 at the same dose used at the last cycle of the induction treatment. Capecitabine plus AK112 plus AK117 will be repeated every 3 weeks until disease progression, unacceptable toxicity or patient's refusal.

Drug: AK112; Drug: AK117; Drug: Oxaliplatin; Drug: Capecitabine

Part 1_Chemotherapy Regimen Selection Stage Group B(AK112+AK117+FOLFOXIRI)

EXPERIMENTAL

AK112+AK117+FOLFOXIRI AK112 and AK117 and FOLFOXIRI(Irinotecan 150-165 mg/sqm iv day 1, Oxaliplatin 85 mg/sqm iv day 1, Leucovorin(LV) 400 mg/sqm iv day 1, 5-fluorouracil(5-FU) 2400-2800 mg/sqm 46-48 hours continuous infusion, starting on day 1) If no progression occurs during AK112 plus AK117 plus FOLFOXIRI, patients will receive maintenance 5-FU/LV plus AK112 plus AK117 at the same dose used at the last cycle of the induction treatment. 5-FU/LV plus AK112 plus AK117 will be repeated biweekly until disease progression, unacceptable toxicity or patient's refusal.

Drug: AK112; Drug: AK117; Drug: Oxaliplatin; Drug: Irinotecan; Drug: Leucovorin; Drug: 5-fluorouracil

Part 1_Expansion Stage Group A(AK112 DS1+Chemotherapy)

EXPERIMENTAL

AK112 (Dose1) +Chemotherapy(Decided by Chemotherapy Regimen Selection Stage) AK112 and XELOX or FOLFOXIRI(the same dosage, frequency and duration with Chemotherapy Regimen Selection Stage)

Drug: AK112; Drug: Oxaliplatin; Drug: Capecitabine; Drug: Irinotecan; Drug: Leucovorin; Drug: 5-fluorouracil

Part 1_Expansion Stage Group B(AK112 DS1+AK117 DS1+Chemotherapy)

EXPERIMENTAL

AK112 (Dose1) +AK117 (Dose1) +Chemotherapy(Decided by Chemotherapy Regimen Selection Stage) AK112 and AK117 and XELOX or FOLFOXIRI(the same dosage, frequency and duration with Chemotherapy Regimen Selection Stage)

Drug: AK112; Drug: AK117; Drug: Oxaliplatin; Drug: Capecitabine; Drug: Irinotecan; Drug: Leucovorin; Drug: 5-fluorouracil

Part 1_Expansion Stage Group C (AK112 DS2+Chemotherapy)

EXPERIMENTAL

AK112 (Dose2)+Chemotherapy(Decided by Chemotherapy Regimen Selection Stage). AK112 and XELOX or FOLFOXIRI(the same dosage, frequency and duration with Chemotherapy Regimen Selection Stage).

Drug: AK112; Drug: Oxaliplatin; Drug: Capecitabine; Drug: Irinotecan; Drug: Leucovorin; Drug: 5-fluorouracil

Part 1_Expansion Stage Group D (AK112 DS2 +AK117 DS2 +Chemotherapy)

EXPERIMENTAL

AK112(Dose2) + AK117(Dose2)+Chemotherapy(Decided by Chemotherapy Regimen Selection Stage) AK112 and AK117 and XELOX or FOLFOXIRI(the same dosage, frequency and duration with Chemotherapy Regimen Selection Stage)

Drug: AK112; Drug: AK117; Drug: Oxaliplatin; Drug: Capecitabine; Drug: Irinotecan; Drug: Leucovorin; Drug: 5-fluorouracil

Part 1_Expansion Stage Group E (AK112 DS2+AK117 DS1+Chemotherapy)

EXPERIMENTAL

AK112(Dose2)+AK117(Dose1)+Chemotherapy(Decided by Chemotherapy Regimen Selection Stage) AK112 and AK117 and XELOX or FOLFOXIRI(the same dosage, frequency and duration with Chemotherapy Regimen Selection Stage)

Drug: AK112; Drug: AK117; Drug: Oxaliplatin; Drug: Capecitabine; Drug: Irinotecan; Drug: Leucovorin; Drug: 5-fluorouracil

Part 1_Extension Stage Group F (AK112 DS1 + mFOLFOX6)

EXPERIMENTAL

AK112 (Dose1) +mFOLFOX6 ( Oxaliplatin 85 mg/sqm IV day 1, Leucovorin 400 mg/sqm IV day 1, 5-fluorouracil(5-FU) 2400 mg/sqm 46-48 hours continuous infusion, starting on day 1). If no progression occurs during AK112 plus mFOLFOX6, patients will receive maintenance 5- FU/LV plus AK112 at the same dose used at the last cycle of the induction treatment. 5-FU/LV plus AK112 will be repeated biweekly until disease progression, unacceptable toxicity or patient's refusal.

Drug: AK112; Drug: Oxaliplatin; Drug: Leucovorin; Drug: 5-fluorouracil

Part 1_Extension Stage Group G (AK112 DS2+mFOLFOX6)

EXPERIMENTAL

AK112 (Dose2) +mFOLFOX6 ( Oxaliplatin 85 mg/sqm IV day 1, Leucovorin 400 mg/sqm IV day 1, 5-fluorouracil(5-FU) 2400 mg/sqm 46-48 hours continuous infusion, starting on day 1) If no progression occurs during AK112 plus mFOLFOX6, patients will receive maintenance 5- FU/LV plus AK112 at the same dose used at the last cycle of the induction treatment. 5-FU/LV plus AK112 will be repeated biweekly until disease progression, unacceptable toxicity or patient's refusal.

Drug: AK112; Drug: Oxaliplatin; Drug: Leucovorin; Drug: 5-fluorouracil

Part 2 cohort 1(AK112)

EXPERIMENTAL

Subjects receive AK112 until disease progression or unacceptable toxicity AK112 (until disease progression, unacceptable toxicity or patient's refusal)

Drug: AK112

Part 2 cohort 2(AK112+AK117)

EXPERIMENTAL

Subjects receive AK117 and AK112 until disease progression or unacceptable toxicity AK112 and AK117 ( until disease progression, unacceptable toxicity or patient's refusal)

Drug: AK112; Drug: AK117

Interventions

AK112 DRUG

AK112 via intravenous (IV) infusion until disease progression or unacceptable toxicity

Part 1_Chemotherapy Regimen Selection Stage Group A(AK112+AK117+XELOX); Part 1_Chemotherapy Regimen Selection Stage Group B(AK112+AK117+FOLFOXIRI); Part 1_Expansion Stage Group A(AK112 DS1+Chemotherapy); Part 1_Expansion Stage Group B(AK112 DS1+AK117 DS1+Chemotherapy); Part 1_Expansion Stage Group C (AK112 DS2+Chemotherapy); Part 1_Expansion Stage Group D (AK112 DS2 +AK117 DS2 +Chemotherapy); Part 1_Expansion Stage Group E (AK112 DS2+AK117 DS1+Chemotherapy); Part 1_Extension Stage Group F (AK112 DS1 + mFOLFOX6); Part 1_Extension Stage Group G (AK112 DS2+mFOLFOX6); Part 2 cohort 1(AK112); Part 2 cohort 2(AK112+AK117)

AK117 DRUG

AK117 via intravenous (IV) infusion until disease progression or unacceptable toxicity

Part 1_Chemotherapy Regimen Selection Stage Group A(AK112+AK117+XELOX); Part 1_Chemotherapy Regimen Selection Stage Group B(AK112+AK117+FOLFOXIRI); Part 1_Expansion Stage Group B(AK112 DS1+AK117 DS1+Chemotherapy); Part 1_Expansion Stage Group D (AK112 DS2 +AK117 DS2 +Chemotherapy); Part 1_Expansion Stage Group E (AK112 DS2+AK117 DS1+Chemotherapy); Part 2 cohort 2(AK112+AK117)

Oxaliplatin DRUG

Oxaliplatin via IV infusion

Part 1_Chemotherapy Regimen Selection Stage Group A(AK112+AK117+XELOX); Part 1_Chemotherapy Regimen Selection Stage Group B(AK112+AK117+FOLFOXIRI); Part 1_Expansion Stage Group A(AK112 DS1+Chemotherapy); Part 1_Expansion Stage Group B(AK112 DS1+AK117 DS1+Chemotherapy); Part 1_Expansion Stage Group C (AK112 DS2+Chemotherapy); Part 1_Expansion Stage Group D (AK112 DS2 +AK117 DS2 +Chemotherapy); Part 1_Expansion Stage Group E (AK112 DS2+AK117 DS1+Chemotherapy); Part 1_Extension Stage Group F (AK112 DS1 + mFOLFOX6); Part 1_Extension Stage Group G (AK112 DS2+mFOLFOX6)

Capecitabine DRUG

Capecitabine via oral,The total daily dose was 2000mg/sqm, Each cycle was administered for 2 consecutive weeks, followed by a week of rest, with a treatment cycle every 21 days

Part 1_Chemotherapy Regimen Selection Stage Group A(AK112+AK117+XELOX); Part 1_Expansion Stage Group A(AK112 DS1+Chemotherapy); Part 1_Expansion Stage Group B(AK112 DS1+AK117 DS1+Chemotherapy); Part 1_Expansion Stage Group C (AK112 DS2+Chemotherapy); Part 1_Expansion Stage Group D (AK112 DS2 +AK117 DS2 +Chemotherapy); Part 1_Expansion Stage Group E (AK112 DS2+AK117 DS1+Chemotherapy)

Irinotecan DRUG

Irinotecan via IV infusion

Part 1_Chemotherapy Regimen Selection Stage Group B(AK112+AK117+FOLFOXIRI); Part 1_Expansion Stage Group A(AK112 DS1+Chemotherapy); Part 1_Expansion Stage Group B(AK112 DS1+AK117 DS1+Chemotherapy); Part 1_Expansion Stage Group C (AK112 DS2+Chemotherapy); Part 1_Expansion Stage Group D (AK112 DS2 +AK117 DS2 +Chemotherapy); Part 1_Expansion Stage Group E (AK112 DS2+AK117 DS1+Chemotherapy)

Leucovorin DRUG

Leucovorin via IV infusion

Part 1_Chemotherapy Regimen Selection Stage Group B(AK112+AK117+FOLFOXIRI); Part 1_Expansion Stage Group A(AK112 DS1+Chemotherapy); Part 1_Expansion Stage Group B(AK112 DS1+AK117 DS1+Chemotherapy); Part 1_Expansion Stage Group C (AK112 DS2+Chemotherapy); Part 1_Expansion Stage Group D (AK112 DS2 +AK117 DS2 +Chemotherapy); Part 1_Expansion Stage Group E (AK112 DS2+AK117 DS1+Chemotherapy); Part 1_Extension Stage Group F (AK112 DS1 + mFOLFOX6); Part 1_Extension Stage Group G (AK112 DS2+mFOLFOX6)

5-fluorouracil DRUG

5-fluorouracil via IV infusion

Part 1_Chemotherapy Regimen Selection Stage Group B(AK112+AK117+FOLFOXIRI); Part 1_Expansion Stage Group A(AK112 DS1+Chemotherapy); Part 1_Expansion Stage Group B(AK112 DS1+AK117 DS1+Chemotherapy); Part 1_Expansion Stage Group C (AK112 DS2+Chemotherapy); Part 1_Expansion Stage Group D (AK112 DS2 +AK117 DS2 +Chemotherapy); Part 1_Expansion Stage Group E (AK112 DS2+AK117 DS1+Chemotherapy); Part 1_Extension Stage Group F (AK112 DS1 + mFOLFOX6); Part 1_Extension Stage Group G (AK112 DS2+mFOLFOX6)

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically proven diagnosis of colorectal adenocarcinoma
• Part1: Subjects who have not previously received any systemic antitumor therapy and who have previously received neoadjuvant or adjuvant therapy, the first detection of recurrence or metastasis should be ≥12 months after the last administration of neoadjuvant or adjuvant therapy
• Part2: Subjects who have previously received systemic therapy including fluorouracil, oxaliplatin, irinotecan, bevacizumab or anti-EGFR antibodies or could not tolerate or have contraindications to standard treatment
• Eastern Cooperative Oncology Group performance status of 0 or 1
• Measurable disease as defined by RECIST v1.1
• Adequate hematologic and organ function

You may not qualify if:

• Known MSI-H(Microsatellite-Instability-High) or dMMR(Mismatch Repair-Deficient)
• Prior treatment with immunotherapy, including immune checkpoint inhibitors , immune checkpoint agonists, immune cell therapy and any treatment targeting tumor immune pathway
• History of autoimmune disease
• Prior allogeneic stem cell or solid organ transplantation
• Positive test for human immunodeficiency virus,Active hepatitis B or hepatitis C
• Receipt of a live, attenuated vaccine within 30 days prior to randomization, during treatment
• Pregnancy or lactation
• Dysphagia

Sponsors & Collaborators

• Akeso: lead
• Summit Therapeutics: collaborator

Study Sites (4)

Summit Therapeutics Research Site

Los Angeles, California, 90067, United States

Location

Summit Therapeutics Research Site

Murrieta, California, 92562, United States

Location

Summit Therapeutics Research Site

Fairfax, Virginia, 22031, United States

Location

The Sixth Hospital,Sun Yat-sen University

Guanzhou, Guangdong, 510000, China

Location

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

Oxaliplatin; Capecitabine; 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; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Camptothecin; Alkaloids; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes; Enzymes and Coenzymes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 16, 2022
• First Posted: May 19, 2022
• Study Start: June 27, 2022
• Primary Completion (Estimated): May 15, 2026
• Study Completion (Estimated): August 12, 2028
• Last Updated: October 14, 2025

Record last verified: 2025-10

Locations

US (3); CN (1)