A Phase III Study to Evaluate the Efficacy and Safety of Penpulimab in the Relapsed and Refractory Classical Hodgkin's Lymphoma

NCT05244642 | Recruiting Phase 3

• 1 other identifier: AK105-303
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 6

Brief Summary

This is an open-label, multicenter, randomized, phase 3 trial to evaluate the efficacy of Penpulimab vs. standard chemotherapy selected by investigator in patients with relapsed or refractory classic Hodgkin's lymphoma.

Conditions

Hodgkin Disease Lymphoma

Outcome Measures

Primary Outcomes (1)

• Progression Free Survival (PFS) assessed by Independent Radiologic Review Committee (IRRC) per Lugano Classification 2014

  Time from the date of randomization to the date of progressive disease (PD) or death, whichever occurs first.

  Up to 2 years

Secondary Outcomes (7)

• Overall Survival (OS)

  Up to end of study

• Objective Response Rate (ORR)

  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

Study Arms (2)

Group A (Penpulimab)

EXPERIMENTAL

Participants receive Penpulimab 200mg intravenously (IV) on Day 1, Q2W for 24 months.

Drug: Penpulimab

Group B (Chemotherapy)

ACTIVE COMPARATOR

Participants receive investigator's choice of chemotherapy Q2W or Q3W for up to 4 or 6 cycles.

Drug: Investigator's choice of Chemotherapy

Interventions

Penpulimab DRUG

A humanized monoclonal immunoglobulin.

Also known as: AK105

Group A (Penpulimab)

Investigator's choice of Chemotherapy DRUG

Participants will receive one of the following chemotherapies, including but not limited to DHAP (cisplatin 100mg/m2 D1, high dose cytarabine 2 mg/m2 q12h D2, dexamethasone 40mg D1-4, Q3W); ESHAP (etoposide 40 mg/m2 D1-4, cisplatin 25 mg/m2 D1-4, high dose cytarabine 2 mg/m2 D5, methylprednisolone 500mg D1-4, Q3W); DICE (dexamethasone 10mg/m2 D1-4, ifosfamide 1.0g/m2 D1-4, cisplatin 25mg/m2 D1-4, etoposide 60 mg/m2 D1-4, Q3W); ICE (ifosfamide 5 mg/m2 D2, carboplatin AUC 5 D2, etoposide 100 mg/m2 D1-3, Q3W); IGEV (ifosfamide 2 mg/m2 D1-4, gemcitabine 800 mg/m2 D1, D4, vinorelbine 20mg/m2 D1, prednisone 100 mg D1-4, Q3W); GVD (gemcitabine 1g/m2 D1, D8, vinorelbine 20 mg/m2 D1, D8, liposome doxorubicin 15 mg/m2 D1, D8, Q3W); MINE (etoposide 65mg/m2 D1-3, ifosfamide 1.33g/m2 D1-3, mitoxantrone 8mg/m2 d1, Q3W); GemOx (gemcitabine 800mg/m2 D1, D8, oxaliplatin 85mg/m2 D1, Q3W); GemOx (gemcitabine 1000mg/m2 D1, oxaliplatin 100mg/m2d1, Q2W).

Group B (Chemotherapy)

Eligibility Criteria

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

You may qualify if:

• Signed written informed consent form (ICF).
• Age of ≥ 18 years at the time of enrollment, male or female.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Life expectancy of ≥ 3 months.
• Histologically confirmed classic Hodgkin's lymphoma (cHL).
• Relapsed (disease progression during or after most recent therapy) or refractory (failure to achieve CR or PR after most recent therapy) cHL and meet any of the following criterions:
• Subjects who have received autologous hematopoietic stem cell transplantation (ASCT) after salvage chemotherapy, followed by relapse or progression.
• For subjects who have not received ASCT, it is required at least 2 lines of prior systemic chemotherapy. Refractory subjects are defined as failure to achieve PR after at least 2 cycles of chemotherapy, or failure to achieve CR after at least 4 cycles of chemotherapy. If the best response to treatment is PD or the reason for ending the treatment is PD, the subject is considered as refractory without requirement on the number of cycles of treatment received.
• Have at least one measurable lesion according to Lugano classification 2014.
• Have adequate hematologic and organ function as defined below:
• Hematology (supportive treatment with ang blood components or cell growth factors is not allowed within 7 days prior to enrollment laboratory test): Absolute neutrophil count (ANC) ≥ 1.0x109/L, platelet count ≥ 75 x109/L, hemoglobin ≥ 80g/L.
• Kidney: Serum creatinine ≤ 1.5 X ULN and estimated GFR (by Cockroft-Gault equation) ≥ 50ml/min.
• Liver: Total bilirubin ≤ 1.5 X ULN, AST/ALT ≤ 2.5 X ULN.
• Coagulation: International normalized ratio (INR) and activated partial thromboplastin time (APTT) ≤ 1.5 × ULN.
• Women of childbearing potential (WOCBP) must be tested for serum or urine pregnancy negative within 3 days prior to the first dose of study treatment. WOCBP will be instructed to adhere to contraception while on treatment and for at least 150 days after the last dose of study treatment. Male subjects who are sexually active with WOCBP will be instructed to adhere to contraception while on treatment and for at least 150 days after receiving the last dose of study treatment.

You may not qualify if:

• Nodular lymphocytes are non-Hodgkin's lymphoma or gray area lymphoma.
• Central nervous system lymphoma invasion.
• Have received any investigational treatment or investigational device within 4 weeks prior to the first dose of study treatment.
• Enrolled in another clinical study at the same time, unless it is an observational (non-interventional) clinical study or in follow-up period for interventional studies.
• The last radiotherapy or last anti-tumor therapy (chemotherapy, tumor embolization, etc.) has been given within 4 weeks prior to the first dose of study treatment.
• Prior exposure to any anti-PD-1, anti-PD-L1, anti-CTLA-4 antibody, or any other antibody or drug target for T cell co-stimulatory or checkpoint pathways, such as ICOS or agonists (e.g., CD40, CD137, GITR and OX40, etc.).
• Subjects with other malignancy within 5 years prior to the first dose of study treatment, except for locally curable cancers that have been apparently cured, such as basal or skin squamous cell carcinoma, superficial bladder cancer, cervix or breast carcinoma in situ.
• Active, known or suspected autoimmune disease, or medical history of autoimmune disease in the past 2 years, with the exceptions of vitiligo, alopecia, graves' disease, psoriasis or eczema not requiring systemic treatment within the last 2 years, asymptomatic but only steady doses of hormone replacement therapy are required for hypothyroidism (caused by autoimmune thyroiditis) or type I diabetes requiring only a steady dose of insulin replacement therapy, or that the primary disease does not relapse without external triggering factors
• Systemic glucocorticoids or other immunosuppressive drugs used within 7 days prior to the first dose of study treatment. It is allowed to use nasal spray, inhaled, or other topical application of glucocorticoids, and a physiological dose of systemic glucocorticoids does not exceed 10 mg/ day or the equivalent. Glucocorticoids are also allowed to temporary use for the treatment of dyspnea symptoms of chronic obstructive pulmonary disease (COPD), or as a prophylactic agent for hypersensitivity reactions.
• Known active human immunodeficiency virus (HIV) positive.
• Known history of primary immunodeficiency.
• Known active tuberculosis.
• Prior solid organ transplantation, allogeneic hematopoietic stem cell transplantation (HSCT).
• ASCT within 90 days prior to the first dose of study treatment.
• History of gastrointestinal perforation and/ or fistula (patients can be enrolled if the gastrointestinal perforation or fistula has been surgically removed), ileus (including incomplete ileus requiring parenteral nutrition), extensive bowel resection (partial colectomy or extensive small bowel resection with chronic diarrhea), Crohn's disease, ulcerative colitis or chronic diarrhea within 6 months prior to the first dose of study treatment.

Sponsors & Collaborators

• Akeso: lead
• Peking University Cancer Hospital & Institute: collaborator

Study Sites (6)

Affiliated Cancer Hospital and Institute of Guangzhou Medical University

Guangzhou, Guangdong, 510095, China

NOT YET RECRUITING

Henan Cancer Hospital

Zhengzhou, Henan, 450003, China

NOT YET RECRUITING

Xiangya Hospital Central South University

Changsha, Hunan, 410008, China

NOT YET RECRUITING

Qilu Hospital of Shandong University

Jinan, Shandong, 250012, China

NOT YET RECRUITING

Tianjin Medical University Cancer Institute and Hospital

Tianjin, Tianjin Municipality, 300060, China

NOT YET RECRUITING

Beijing Cancer Hospital

Beijing, 100142, China

RECRUITING

MeSH Terms

Interventions

penpulimab

Study Officials

• Yuqin Song, MD

  Peking University Cancer Hospital & Institute

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Zhifang Yao, MD

CONTACT

86-0760-89873999; clinicaltrials@akesobio.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 25, 2022
• First Posted: February 17, 2022
• Study Start: February 15, 2022
• Primary Completion: December 30, 2025
• Study Completion: March 30, 2026
• Last Updated: February 17, 2022

Record last verified: 2022-02

Data Sharing

• IPD Sharing: Will not share

Locations

CN (6)