A Phase Ib/II Study of AK112 in Combination With AK117 in Advanced Malignant Tumors

Akeso

Status and phase: Active, not recruiting; Phase 2; Phase 1

Conditions: Advanced Malignant Tumors

Treatments: Drug: AK112; Drug: Gemcitabine; Drug: 5-Fluorouracil; Drug: AK117; Drug: Carboplatin; Drug: Cisplatin

Study type: Interventional

Funder types: Industry

Identifiers

NCT05229497

AK117-201

Details and patient eligibility

About

Phase Ib/II open label, multicenter study to evaluate the efficacy and safety of AK112 (anti-PD-1 and VEGF bispecific antibody) combined with AK117#AntiCD47 Antibody# in advanced malignant tumors

Enrollment: 154 estimated patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. 18 to 75 years old.

2. Have a life expectancy of at least 3 months.

3. Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

4. Phase Ib: Histologically or cytologically confirmed selected advanced solid tumor.

5. Phase II: Subjects were patients with recurrent/metastatic HNSCC diagnosed histologically and/or cytologically that could not be completely resected surgically and could not be treated with radical simultaneous radiotherapy, or local and or neck recurrence after radical surgery that had progressed with radiotherapy or were unsuitable for radiotherapy.

   Cohort 1 and 2 :

   Recurrent or metastatic HNSCC (non-nasopharyngeal carcinoma) that has not received systemic antitumour therapy for previous recurrent or metastatic stage and has positive PD-L1 expression (CPS ≥ 1); for subjects who have received previous adjuvant/neoadjuvant chemotherapy for non-metastatic disease with curative intent or radical radiotherapy for locally advanced disease, if disease progression occurs after the end of the last chemotherapy session ≥ 6 months, are eligible to participate in this cohort.

   Cohort 3: Recurrent or metastatic HNSCC (non-nasopharyngeal carcinoma) that has not received systemic antitumour therapy for prior recurrent or metastatic stages; for subjects who have received prior adjuvant/neoadjuvant chemotherapy for non-metastatic disease with curative intent, or radical radiotherapy for locally advanced disease, are eligible to participate in this cohort if disease progression occurs ≥6 months after the end of the last chemotherapy treatment.

   Cohort 4: Recurrent or metastatic nasopharyngeal carcinoma that has not received systemic antitumour therapy for prior recurrent or metastatic stages; for subjects who have received prior adjuvant/neoadjuvant chemotherapy for non-metastatic disease with curative intent or radical radiotherapy for locally advanced disease, they are eligible for this cohort if disease progression occurs ≥ 6 months after the end of the last chemotherapy treatment. Note: Subjects with recurrent or residual primary foci after radiotherapy are excluded, and subjects with adenocarcinoma or sarcoma of the nasopharynx are excluded.

6. Have at least one measurable lesion based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 assessed by investigator.

7. Has adequate organ function.

Exclusion criteria

1. Undergone major surgery within 30 days prior to the first dose of study treatment.
2. Active central nervous system (CNS) metastases.
3. History of active autoimmune disease that has required systemic treatment in the past 2 years (i.e.,corticosteroids or immunosuppressive drugs).
4. Active Hepatitis B or Hepatitis C.
5. Received previous immunotherapy, including immune checkpoint inhibitors, immune checkpoint agonists, immune cell therapy and other treatments targeting the mechanism of tumor immunity.
6. History of severe bleeding tendency or coagulation disorder.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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154 participants in 7 patient groups

Phase Ib#Dosage regimen 1#

Experimental group

Description:

Subjects receive AK112 (20 mg/kg Q3W) + AK117 (30 mg/kg QW)

Treatment:

Drug: AK117

Drug: AK112

Phase Ib#Dosage regimen 2#

Experimental group

Description:

Subjects receive AK112 (20 mg/kg Q3W) + AK117 (45 mg/kg QW)

Treatment:

Drug: AK117

Drug: AK112

Phase II#Cohort 1#

Experimental group

Description:

Head and neck squamous cell carcinoma (HNSCC): AK112 (20 mg/kg Q3W)

Treatment:

Drug: AK112

Phase II#Cohort 2#

Experimental group

Description:

HNSCC: AK112 (20 mg/kg Q3W) + AK117 (recommended Phase 2 dose)

Treatment:

Drug: AK117

Drug: AK112

Phase II#Cohort 3#

Experimental group

Description:

HNSCC: AK112 (20 mg/kg Q3W) + AK117 (recommended Phase 2 dose)+Carboplatin/Cisplatin+5-fluorouracil

Treatment:

Drug: Cisplatin

Drug: Carboplatin

Drug: AK117

Drug: 5-Fluorouracil

Drug: AK112

Phase II#Cohort 4 regimen 1#

Experimental group

Description:

Nasopharyngeal Carcinoma: AK112 (10 mg/kg d1 Q3W) + AK117（recommended Phase 2 dose）+ Cisplatin (80 mg/m2 d1 Q3W)+Gemcitabine (1000 mg/m2 d1, d8 Q3W)

Treatment:

Drug: Cisplatin

Drug: AK117

Drug: Gemcitabine

Drug: AK112

Phase II#Cohort 4 regimen 2#

Experimental group

Description:

Nasopharyngeal Carcinoma: AK112 (10 mg/kg d1 Q3W) + Cisplatin (100 mg/m2 d1 Q3W)+Gemcitabine (1000 mg/m2 d1, d8 Q3W)

Treatment:

Drug: Cisplatin

Drug: Gemcitabine

Drug: AK112