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

Akeso

Status and phase: Enrolling; Phase 2

Conditions: Metastatic Colorectal Cancer

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

Study type: Interventional

Funder types: Industry

Identifiers

NCT05382442

AK112-206

Details and patient eligibility

About

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.

Enrollment: 254 estimated patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• 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

Exclusion criteria

• 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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254 participants in 11 patient groups

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

Experimental group

Description:

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.

Treatment:

Drug: Capecitabine

Drug: AK112

Drug: AK117

Drug: Oxaliplatin

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

Experimental group

Description:

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.

Treatment:

Drug: AK112

Drug: AK117

Drug: Irinotecan

Drug: Oxaliplatin

Drug: 5-fluorouracil

Drug: Leucovorin

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

Experimental group

Description:

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)

Treatment:

Drug: Capecitabine

Drug: AK112

Drug: Irinotecan

Drug: Oxaliplatin

Drug: 5-fluorouracil

Drug: Leucovorin

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

Experimental group

Description:

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)

Treatment:

Drug: Capecitabine

Drug: AK112

Drug: AK117

Drug: Irinotecan

Drug: Oxaliplatin

Drug: 5-fluorouracil

Drug: Leucovorin

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

Experimental group

Description:

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).

Treatment:

Drug: Capecitabine

Drug: AK112

Drug: Irinotecan

Drug: Oxaliplatin

Drug: 5-fluorouracil

Drug: Leucovorin

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

Experimental group

Description:

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)

Treatment:

Drug: Capecitabine

Drug: AK112

Drug: AK117

Drug: Irinotecan

Drug: Oxaliplatin

Drug: 5-fluorouracil

Drug: Leucovorin

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

Experimental group

Description:

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)

Treatment:

Drug: Capecitabine

Drug: AK112

Drug: AK117

Drug: Irinotecan

Drug: Oxaliplatin

Drug: 5-fluorouracil

Drug: Leucovorin

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

Experimental group

Description:

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.

Treatment:

Drug: AK112

Drug: Oxaliplatin

Drug: 5-fluorouracil

Drug: Leucovorin

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

Experimental group

Description:

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.

Treatment:

Drug: AK112

Drug: Oxaliplatin

Drug: 5-fluorouracil

Drug: Leucovorin

Part 2 cohort 1(AK112)

Experimental group

Description:

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

Treatment:

Drug: AK112

Part 2 cohort 2(AK112+AK117)

Experimental group

Description:

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

Treatment:

Drug: AK112

Drug: AK117