Neoplasms

Symptoms and General Pathology

All Conditions

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Rare Diseases

Neoplasm Metastasis

Carcinoma

Recurrence

Carcinoma, Renal Cell

Kidney Neoplasms

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Adenocarcinoma

Urologic Neoplasms

Urogenital Neoplasms

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Kidney Diseases

Urologic Diseases

Male Urogenital Diseases

Renal Cell Carcinoma

Clear Cell Renal Cell Carcinoma

All Drugs and Chemicals

Antineoplastic Agents

Immunomodulating Agents

Nivolumab

Ipilimumab

Relatlimab

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Neoadjuvant 2 cycles of nivolumab 360mg every 3 weeks

Neoadjuvant 2 cycles of nivolumab 3 mg/kg + ipilimumab 1 mg/kg every 3 weeks

Neoadjuvant 2 cycles of nivolumab 360mg + relatlimab 360mg every 3 weeks

Patients will receive 2 cycles of nivolumab 360mg (arm A and C) or 3mg/kg (arm B) every 3 weeks followed by a nephrectomy.

Neoadjuvant nivolumab

Patients will receive 2 cycles of ipilimumab 1mg/kg every 3 weeks followed by a nephrectomy.

Neoadjuvant ipilimumab

Patients will receive 2 cycles of relatlimab 360mg every 3 weeks followed by a nephrectomy.

Neoadjuvant relatlimab

John Haanen, Prof

Femke Burgers, MD

Axel Bex, Prof

The NESCIO-trial is a multicenter, randomized, open-label, three-arm phase II trial investigating different combinations of neoadjuvant immunotherapy in patients with primary, resectable, intermediate to high-risk, clear-cell renal cell carcinoma. In this trial patients will be randomized 1:1:1 to receive either 2 cycles of nivolumab 360mg every 3 weeks (arm A), 2 cycles of ipilimumab 1 mg/kg + nivolumab 3 mg/kg every 3 weeks (arm B) or 2 cycles of relatlimab 360mg + nivolumab 360mg every 3 weeks (arm C), prior to surgery at week 7.

After 42 patients (14 per arm) have been recruited, an interim analysis will be performed to evaluate the observed efficacy and toxicity within each arm and either allow for early discontinuation of the treatment or continuing recruitment for the second stage. As the primary endpoint, the pathological response (decrease in tumor) will be evaluated. If at most one pathologic response in the primary tumor is observed, the treatment arm will be closed for insufficient activity on the primary tumor. If at least 2 pathologic responses are observed, 9 additional patients will be included to a total of 23 patients per cohort. A maximum of 69 patients will be recruited for this study.

Follow up will start at week 12 with a CT-scan according to the national/center's standard. Patients will be evaluated every 3 months by physical examination and lab testing for up to two years, thereafter according to institutional guidelines up to 5 years following surgery.

Open-label three-arm randomized phase II trial

Neoadjuvant Study With Combination Immuno-oncology for Primary Clear Cell Renal Cell Cancer

Prospective, Randomized, Neoadjuvant Phase II Study With Combination Immuno-oncology in Primary Clear Cell Renal Cancer at Risk for Recurrence or Distant Metastases (NESCIO-trial)

Pathologic response rate is defined as the proportion of patients demonstrating a complete pathologic or partial pathologic response, according to central revision (pathology of NKI)

ORR is defined as the proportion of patients demonstrating a complete or partial response according to RECIST 1.1

RFS is defined as the time from randomization to recurrence or death from any cause, whichever occurs first. Subjects last known to be alive, who have not experience recurrence, will be censored.

EFS is defined as the time from randomization to recurrence, distant metastasis, or death from any cause, whichever occurs first. Subjects who are event-free at the end of follow-up will be censored.

The proportion of patients starting treatment who experience distant metastases during follow-up.

The proportion of patients starting treatment who experience a local recurrence during follow-up.

Surgical complication rates according to Clavien-Dindo classification

Bristol-Myers Squibb

The Netherlands Cancer Institute

Head and Neck Neoplasms

Cisplatin

* Neoadjuvant dose with Nivolumab 3mg/kg after randomization within 2 weeks before surgery
* Surgical resection of primary tumor including neck dissection according to standard of care
* 6-7 weeks risk-adapted adjuvant radio(-chemo)therapy 56-66 Gy (chemotherapy Cisplatin 100 mg/m2 on days 1, 22, 43, or Cisplatin once weekly (40mg/m2) for high risk patients only), start within 6 weeks post-surgery

Arm Ia:

• Adjuvant administration of Nivolumab 3mg/kg i.v. d1 every 2 weeks within 6 weeks after end of radiotherapy until progression or up to 6 months

Arm Ib:

• Adjuvant administration of Nivolumab 3mg/kg i.v. d1 every 2 weeks and Ipilimumab 1mg/kg i.v. d1 every 6 weeks within 6 weeks after end of radiotherapy until progression or up to 6 months

* Surgical resection of primary tumor including neck dissection according to standard of care
* 6-7 weeks risk-adapted adjuvant radio(-chemo)therapy 56-66 Gy (chemotherapy Cisplatin 100 mg/m2 on days 1, 22, 43 or Cisplatin once weekly (40mg/m2) in high risk patients), start within 6 weeks post-surgery
* Standard follow-up

Surgical resection of primary tumor including neck dissection according to standard of care

Surgical resection of primary tumor

Risk-adapted adjuvant radio(-chemo)therapy 56-66 Gy (chemotherapy Cisplatin 100 mg/m2 on days 1, 22, 43, or Cisplatin once weekly (40mg/m2) for high risk patients only)

Adjuvant radio(-chemo)therapy

Neoadjuvant dose with Nivolumab 3mg/kg after randomization within 2 weeks before surgery

Neoadjuvant Nivolumab

Administration of Nivolumab 3mg/kg i.v. d1 every 2 weeks within 6 weeks after end of radiotherapy until progression or up to 6 months

Adjuvant Nivolumab

Administration of Nivolumab 3mg/kg i.v. d1 every 2 weeks and Ipilimumab 1mg/kg i.v. d1 every 6 weeks within 6 weeks after end of radiotherapy until progression or up to 6 months

Adjuvant Nivolumab and Ipilimumab

PD Dr. med. Chia-Jung Busch

Multicenter randomized controlled phase III study of nivolumab alone or in combination with ipilimumab as immunotherapy vs standard follow-up in surgical resectable HNSCC after adjuvant therapy

Surgically treated locally advanced head and neck squamous cell carcinoma often requires postoperative chemoradiation with high risk of acute and late toxicity. DFS after 2 years is approximately 70%. Combining anti-PD-1 and anti-CTLA4 as a maintenance therapy may improve DFS due to anti-tumor effects of immunotherapy by enhancing cross-presentation of tumor antigens.

Arm Ia and Arm Ib are summarized in one Arm, due to central ethics committee, as they both include neoadjuvant and adjuvant treatment compared to Arm II

Study of Nivolumab Alone or in Combination With Ipilimumab as Immunotherapy vs Standard Follow-up in Surgical Resectable HNSCC After Adjuvant Therapy

Multicenter Randomized Controlled Phase III Study of Nivolumab Alone or in Combination With Ipilimumab as Immunotherapy vs Standard Follow-up in Surgical Resectable HNSCC After Adjuvant Therapy

disease free survival (DFS) at 3 years of nivolumab alone or in combination with ipilimumab as adjuvant immunotherapy after adjuvant radio(chemo)therapy in locally advanced resected HNSCC

Disease assessment (CT/ MRI) and Panendoscopy and FFPE in case of suspicion or recurrence

Follow Up- Visits after end of treatment every 3 months until month 36 after randomization, afterwards every 6 months

We compare disease free survival, defined as time from randomization to date of first observed either histologically proven recurrence (local, locoregional or distant), or death from any cause whatever occurs first, of arm Ia to arm II and of arm Ib to arm II

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Neoadjuvant Study With Combination Immuno-oncology for Primary Clear Cell Renal Cell Cancer	NCT05148546	Renal Cell Carc...	Neoadjuvant niv... Neoadjuvant ipi... Neoadjuvant rel...	18 Years -	The Netherlands Cancer Institute
Study of Nivolumab Alone or in Combination With Ipilimumab as Immunotherapy vs Standard Follow-up in Surgical Resectable HNSCC After Adjuvant Therapy	NCT03700905	Head and Neck C...	Surgical resect... Adjuvant radio(... Neoadjuvant Niv... Adjuvant Nivolu... Adjuvant Nivolu...	18 Years -	Universitätsklinikum Hamburg-Eppendorf
Neoadjuvant Study With Combination Immuno-oncology for Primary Clear Cell Renal Cell Cancer	NCT05148546	Renal Cell Carc...	Neoadjuvant niv... Neoadjuvant ipi... Neoadjuvant rel...	18 Years -	The Netherlands Cancer Institute

Spots Global Cancer Trial Database for neoadjuvant nivolumab