Symptoms and General Pathology

All Conditions

Neoplasms

Mouth and Tooth Diseases

Ear, Nose, and Throat Diseases

Rare Diseases

Recurrence

Nasopharyngeal Carcinoma

Disease Attributes

Antineoplastic Agents

All Drugs and Chemicals

Avelumab

Axitinib

Antineoplastic Agents, Immunological

Protein Kinase Inhibitors

Enzyme Inhibitors

Axitinib: 5 mg bd po Day 1 to Day 28

Avelumab: 10mg/kg Day 1 and Day 15 every 4 weeks

Avelumab: 10 mg/kg Day 1 to Day 15 every 4 weeks

Anthony Chan, MD

Nasopharyngeal cancer (NPC) is the most common head and neck cancer in South China and South East Asia. Worldwide, there are 80,000 incident cases and 50,000 deaths annually. In Hong Kong, NPC ranked as the tenth most common cancer in man. Up to 30% of NPC patients will develop recurrence or metastases after primary radiotherapy or chemoradiation. Platinum-based chemotherapy regimen has been the main stay of first line treatment for recurrent or metastatic NPC. However, the duration of response is short and currently there is no recommended standard second line chemotherapy. Axitinib is a highly potent and selective inhibitor of VEGF receptor. Selectively targeting a single growth factor receptor pathway provides the potential to rationally adjust dosages and combine drugs directed at specific parts of the pathway to minimize toxicity and achieve the optimum therapeutic benefit. In the phase 2 axitinib monotherapy in recurrent or metastatic NPC who failed at least one line of chemotherapy, the clinical benefit rate (CBR, complete response + partial response + stable disease) was 78.4% at 3 months but decreased to 43.2% at 6 months. However, the confirmed objective response rate (ORR) by RECIST was only 2.7% and unconfirmed ORR of 18.9%, with no complete response.Recently, the promising clinical activity of immune check point inhibitors has been demonstrated in NPC. The ORR was 25.9% (7 partial responses out of 27 patients) for single agent pembrolizumab, and 20.5% (including 1 complete response and 7 partial responses out of 44 patients) for single agent nivolumab,9 in recurrent or metastatic NPC who failed at least first line chemotherapy.

The combination of axitinib and avelumab has been studied in renal cell carcinoma (RCC). Based on the above promising and positive results in renal cell carcinoma (RCC) and head and neck squamous cell carcinomas (HNSCC), the investigators hypothesize that the combination of axitinib and avelumab in the second line setting of NPC will achieving a more complete, deep and durable response than either agent alone, without a significant increase in toxicity.

This is an open-label, single arm, phase 2 clinical trial evaluating the activity and safety of the combination of axitinib and avelumab in recurrent or metastatic NPC patients who failed at least one line of platinum-based chemotherapy.

NPC - AXEL Study : Axitinib-Avelumab

AXEL: Axitinib-Avelumab Combination in Recurrent or Metastatic Nasopharyngeal Cancer: a Multicenter Phase 2 Trial

Chinese University of Hong Kong

Director, CCTU, Department of Clinical Oncology, CUHK

Gemcitabine

Cisplatin

Gemcitabine 1000 mg/m² IV are given on Days 1 \& 8, and cisplatin 80 mg/m² IV are given on Day 1 of each cycle，placebo will be administered at the dose of 240 mg Q3W before that. Chemotherapy is given Q3W for up to 6 cycles and placebo for up to 2 years

Gemcitabine 1000 mg/m² IV are given on Days 1 \& 8, and cisplatin 80 mg/m² IV are given on Day 1 of each cycle，JS001 will be administered at the dose of 240 mg Q3W before that. Chemotherapy is given Q3W for up to 6 cycles and JS001 for up to2years

TORIPALIMAB INJECTION(JS001 ) combine with chemotherapy

Placebos

Ruihua Xu, Ph.D

This is a randomized, placebo-controlled, multi-center, double blinded, Phase III study to determine the efficacy and safety of TORIPALIMAB INJECTIO（JS001） in combination with gemcitabine/cisplatin compared with placebo in combination with gemcitabine/cisplatin as first-line treatment in patients with histological/cytological confirmation of recurrent or metastatic NPC. The primary endpoint is PFS in all patients. Approximately 280 patients who fulfill all of the inclusion criteria and none of the exclusion criteria will be randomized in a 1:1 ratio to one of the two treatment arms. patients will be randomly assigned to the combination of JS001 (Arm A) or placebo (Arm B) with gemcitabine and cisplatin given every 3 weeks (Q3W) in 3-week cycles.

Total 289 patients were enrolled and randomized in a 1:1 ratio to the group of JS001 (Arm A) with gemcitabine and cisplatin or placebo (Arm B) with gemcitabine and cisplatin every 3 weeks (Q3W) in the 'during chemotherapy' phase. During the 'post-chemotherapy' phase, patients randomized to Arm A or Arm B will continue treatment with JS001 or placebo as maintenance therapy Q3W until excessive toxicity or progressive disease, withdrawal of consent or Investigator's judgement or a maximum of 2 years. Tumor evaluation scans will be performed at screening (as baseline) then every 6weeks in the first 12 months then every 9 weeks thereafter until objective disease progression. The primary objective is to compare PFS as assessed by the IRC in ITT population (all randomized patients).

The Efficacy and Safety Study of TORIPALIMAB INJECTION Combined With Chemotherapy for Nasophapyngeal Cancer

A Phase III, Randomized, Placebo Controlled, Multicenter, Double-Blind Study Comparing Toripalimab Injection (JS001) Combined With Chemotherapy Versus Placebo Combined With Chemotherapy for Recurrent or Metastatic Nasopharyngeal Cancer

To evaluate the efficacy of JS001 plus chemotherapy compared with placebo plus chemotherapy，as measured by IRC-assessed progression free survival (PFS) according to RECIST v1.1 in all patients.

The definition of Progressive Disease: At least a 20% increasein the sum of diameters of target lesions, taking as reference the smallest sum on study (thisincludes the baseline sum if that is the smallest on study). In addition to the relative increase of20%, the sum must also demonstrate an absolute increase of at least 5 mm. or the appearance of one or more new lesions is also considered progression.

To evaluate the efficacy of TORIPALIMAB INJECTION(JS001 )plus chemotherapy compared with placebo plus chemotherapy, as measured by overall survival (OS).

an AnticipatedReporting Date of final OS in 2023.

To evaluate the efficacy of TORIPALIMAB INJECTION(JS001) plus chemotherapy compared with placebo plus chemotherapy, as measured by investigator-assessed overall response rate (ORR) according to RECIST v1.1.

To evaluate the efficacy of TORIPALIMAB INJECTION(JS001 )plus chemotherapy compared with placebo plus chemotherapy, as measured by investigator-assessed duration of response (DoR) according to RECIST v1.1.

To evaluate the efficacy of TORIPALIMAB INJECTION(JS001) plus chemotherapy compared with placebo plus chemotherapy, as measured by investigator-assessed disease control rate (DCR) according to RECIST v1.1.

To evaluate the efficacy of JS001 plus chemotherapy compared with placebo plus chemotherapy, as measured by Investigators-assessed PFS according to RECIST v1.1

To evaluate the PFS rate at 1 and 2 years in each treatment arm by investigator

To evaluate the OS rate at 1 and 2 years in each treatment arm

health related quality of life (HRQoL) in patients treated with JS001 plus chemotherapy compared with placebo plus chemotherapy using the EORTC QLQ-C30 \&EORTC QLQ-H\&N35ECOG

health related quality of life (HRQoL) in patients treated with JS001 plus chemotherapy compared with placebo plus chemotherapy using the EORTC QLQ-H\&N35

To evaluate the efficacy of JS001 plus chemotherapy compared with placebo plus chemotherapy, as measured by IRC-assessed duration of response (DoR) according to RECIST v1.1.

To evaluate the efficacy of JS001 plus chemotherapy compared with placebo plus chemotherapy, as measured by IRC-assessed disease control rate (DCR) according to RECIST v1.1.

Incidence of serious adverse events(SAE) as assessed by CTCAE version 5.0

To evaluate the incidence and titers of ADAs against JS001 and to explore the potential relationship of the immunogenicity response with pharmacodynamics, safety and efficacy.

To evaluate PFS of JS001 plus chemotherapy compared with placebo plus chemotherapy according to irRECIST.

To evaluate ORR of JS001 plus chemotherapy compared with placebo plus chemotherapy according to irRECIST.

To evaluate DoR of JS001 plus chemotherapy compared with placebo plus chemotherapy according to irRECIST.

To evaluate DCR of JS001 plus chemotherapy compared with placebo plus chemotherapy according to irRECIST.

Shanghai Junshi Bioscience Co., Ltd.

Safety data are based on the 30 May 2020 cut-off date

Placebos: placebo combine with chemotherapy

Placebo Combine With Chemotherapy

TORIPALIMAB INJECTION(JS001 ) combine with chemotherapy: TORIPALIMAB INJECTION(JS001 ) combine with chemotherapy

TORIPALIMAB INJECTION(JS001 )Combine With Chemotherapy

Total

Age, Categorical

Age, Continuous

Sex: Female, Male

Asian

Race/Ethnicity, Customized

Singapore

China

Taiwan

Region of Enrollment

Xiaojun Wang

IRC-assessed Progression-Free Survival (PFS) According to RECIST v1.1

Investigator-assessed ORR According to RECIST v1.1

Investigator-assessed DoR According to RECIST v1.1

Investigator-assessed DCR According to RECIST v1.1

Investigator-assessed PFS According to RECIST v1.1

Investigator-assessed PFS Rate at 1 and 2 Years

OS Rate at 1 and 2 Years

Patient-Reported Outcome (PRO) Using EORTC QLQ-C30, EORTC QLQ-H&N35 and ECOG Performance Status Assessments

IRC-assessed ORR According to RECIST v1.1

IRC-assessed DoR According to RECIST v1.1

IRC-assessed DCR According to RECIST v1.1

Safety Variables Will be Monitored and Reported:AE.SAE.Vital Signs,Physical Examinations,Laboratory Variable,ECG

ADAs

PFS Assessed Per irRECIST

ORR Assessed Per irRECIST

DoR Assessed Per irRECIST

DCR Assessed Per irRECIST

In the during-chemotherapy phase, placebo will be given before gemcitabine and cisplatin, placebo will be administered at the dose of 240 mg Q3W,gemcitabine 1000 mg/m² IV over 30 minutes are given on Days 1 \& 8, and cisplatin 80 mg/m² IV over 4 hours are given on Day 1 of each cycle. Chemotherapy is given Q3W for up to 6 cycles.During the post-chemotherapy phase, placebo and best supportive care (BSC) can be continued Q3W until excessive toxicity or progressive disease, withdrawal of consent, at the discretion of the Investigator or for a maximum of 2 years.

In the during-chemotherapy phase, JS001 will be given before gemcitabine and cisplatin, JS001 will be administered at the dose of 240 mg Q3W,gemcitabine 1000 mg/m² IV over 30 minutes are given on Days 1 \& 8, and cisplatin 80 mg/m² IV over 4 hours are given on Day 1 of each cycle. Chemotherapy is given Q3W for up to 6 cycles .

During the post-chemotherapy phase, JS001 and best supportive care (BSC) can be continued Q3W until excessive toxicity or progressive disease, withdrawal of consent, at the discretion of the Investigator or for a maximum of 2 years.

Overall Study

Carcinoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Nasopharyngeal Neoplasms

Pharyngeal Neoplasms

Otorhinolaryngologic Neoplasms

Head and Neck Neoplasms

Nasopharyngeal Diseases

Pharyngeal Diseases

Stomatognathic Diseases

Otorhinolaryngologic Diseases

starting dose of 5 mg twice daily for 4 consecutive weeks without interruption.

axitinib

Anthony TC Chan, MD, FRCP

This is an open-label, single arm, phase 2 clinical trial evaluating the activity and safety of single-agent axitinib in recurrent or metastatic NPC patients who failed at least one line of platinum based chemotherapy.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
NPC - AXEL Study : Axitinib-Avelumab	NCT04562441	Recurrent or Me...	Axitinib Avelumab	18 Years -	Chinese University of Hong Kong
The Efficacy and Safety Study of TORIPALIMAB INJECTION Combined With Chemotherapy for Nasophapyngeal Cancer	NCT03581786	Recurrent or Me...	TORIPALIMAB INJ... Placebos	18 Years - 75 Years	Shanghai Junshi Bioscience Co., Ltd.
The Efficacy and Safety Study of TORIPALIMAB INJECTION Combined With Chemotherapy for Nasophapyngeal Cancer	NCT03581786	Recurrent or Me...	TORIPALIMAB INJ... Placebos	18 Years - 75 Years	Shanghai Junshi Bioscience Co., Ltd.
Nasopharyngeal Carcinoma (NPC) Axitinib	NCT01249547	Recurrent or Me...	axitinib	18 Years -	Chinese University of Hong Kong

Spots Global Cancer Trial Database for recurrent or metastatic npc