Cemiplimab as Maintenance Treatment for Advanced Adrenocortical Cancer

NCT07085572 | Recruiting Phase 2 DMC

• 2 other identifiers: NP 65022024-520449-21-00
• Study Type: interventional
• Target: 31
• Locations: 1 country
• Sites: 1

Brief Summary

This clinical trial is a single-arm, non-randomized, prospective phase II study. The study aims to evaluate if the maintenance immunotherapy with cemiplimab in patients with AdrenoCortical Carcinoma (ACC), who obtained disease response or stabilization after first-line chemotherapy, may delay/prevent disease progression. The study will be conducted at ASST Spedali Civili Hospital, Brescia - Italy.

Conditions

Adrenal Cortical Carcinoma

Outcome Measures

Primary Outcomes (1)

• Evaluation of efficacy of cemiplimab as a maintenance immunotherapy on PFS in patients with advanced ACC with no disease progression after 4-6 EDP-M cycles

  Proportion of patients free from progression at 6 months after the end of first-line chemotherapy

  36 months

Secondary Outcomes (3)

• Evaluation of the effect of cemiplimab as a maintenance therapy on Overall Survival (OS)

  36 months

• Evaluation of the effect of cemiplimab on patients' Quality of Life (QoL)

  36 months

• Evaluation of the safety profile of maintenance cemiplimab therapy

  36 months

Other Outcomes (1)

• Evaluation the safety of adding cemiplimab to standard mitotane therapy (Safety run-in phase)

  At the end of Cycle 1 (each cycle is 21 days) for the first six patients enrolled.

Study Arms (1)

Cemiplimab added to the standard maintenance therapy with mitotane

EXPERIMENTAL

Drug: Cemiplimab

Interventions

Cemiplimab DRUG

350 mg IV Q3W

Cemiplimab added to the standard maintenance therapy with mitotane

Eligibility Criteria

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

You may qualify if:

• Male and females \>18 years of age;
• Patients with histologically confirmed ACC;
• Previous induction therapy with EDP-M followed by cytoreductive surgery if indicated;
• No disease progression after first line 4-6 EDP-M cycles;
• An ECOG PS of 0, 1;
• Adequate organ and bone marrow function documented by:
• Hemoglobin \>9.0 g/dL
• ANC \>1.5 x 109/L
• Platelet count \>75 x 109/L
• Serum creatinine \<1.5 ULN or estimated CrCl \>30 mL/min
• Adequate hepatic function:
• Total bilirubin \<1.5 x ULN;
• AST and ALT both \<3 x ULN;
• ALP \<2.5 x ULN; Note: For patients with Gilbert's syndrome, total bilirubin ≤3x ULN. Gilbert's syndrome must be documented appropriately as past medical history.
• Women of child-bearing potential (physiologically capable of becoming pregnant) that must agree to follow instructions for methods of contraception (including at least one highly effective contraception method, see study protocol) for the duration of treatment with study drug, and after discontinuation of treatment as long as mitotane plasma levels are detectable and, in any case, at least for 6 months post treatment completion; must have a negative serum or urine pregnancy test within 24 hours prior to the start of study drug;

You may not qualify if:

• History of recent or active prior malignancy, except for cured non-melanoma skin cancer, cured in situ cervical carcinoma, breast ductal carcinoma in situ, or other treated malignancies where there has been no evidence of disease for at least 5 years;
• Prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another co-inhibitory T-cell receptor;
• Administration of a live vaccine within 30 days of the first dose of study treatment;
• Active autoimmune disease that has required systemic treatment in past 2 years (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs);
• Diagnosis of immunodeficiency or systemic steroid therapy (i.e., dosing exceeding 10 mg of prednisone or equivalent). In case of mitotane treatment, a maximum steroid supplementation of 75 mg of cortone acetate (or equivalent hydrocortisone dose) will be accepted;
• Uncontrolled HIV, Hepatitis B or Hepatitis C (see protocol for details);
• History of (non-infectious) pneumonitis that required steroids or current pneumonitis;
• Active infection requiring systemic therapy;
• Significant cardiovascular disease, such as: history of myocardial infarction, acute coronary syndrome or coronary angioplasty / stenting / bypass grafting within the last 6 months OR CHF NYHA Class II-IV or history of CHF NYHA Class III or IV;
• Pregnancy or breastfeeding;
• Continued sexual activity in women of childbearing potential (physiologically capable of becoming pregnant) or sexually active men who are unwilling to practice highly effective contraception (including at least one highly effective contraception method, see study protocol) prior to the initial dose/start of the first treatment, during the study, and for at least 6 months after the last dose;
• History of active tuberculosis (TB, Bacillus Tuberculosis);
• Untreated brain metastasis that may be considered active.
• Known hypersensitivity or allergy to any of the excipients in the cemiplimab drug product.
• Patients with a history of solid organ transplant (exception: corneal transplant)

Sponsors & Collaborators

• Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia: lead

Study Sites (1)

S.C. Oncologia - ASST Spedali Civili di Brescia

Brescia, Brescia, 25123, Italy

RECRUITING

Related Publications (15)

• Powles T, Park SH, Caserta C, Valderrama BP, Gurney H, Ullen A, Loriot Y, Sridhar SS, Sternberg CN, Bellmunt J, Aragon-Ching JB, Wang J, Huang B, Laliberte RJ, di Pietro A, Grivas P. Avelumab First-Line Maintenance for Advanced Urothelial Carcinoma: Results From the JAVELIN Bladder 100 Trial After >/=2 Years of Follow-Up. J Clin Oncol. 2023 Jul 1;41(19):3486-3492. doi: 10.1200/JCO.22.01792. Epub 2023 Apr 18.

  PMID: 37071838 BACKGROUND

• Powles T, Park SH, Voog E, Caserta C, Valderrama BP, Gurney H, Kalofonos H, Radulovic S, Demey W, Ullen A, Loriot Y, Sridhar SS, Tsuchiya N, Kopyltsov E, Sternberg CN, Bellmunt J, Aragon-Ching JB, Petrylak DP, Laliberte R, Wang J, Huang B, Davis C, Fowst C, Costa N, Blake-Haskins JA, di Pietro A, Grivas P. Avelumab Maintenance Therapy for Advanced or Metastatic Urothelial Carcinoma. N Engl J Med. 2020 Sep 24;383(13):1218-1230. doi: 10.1056/NEJMoa2002788. Epub 2020 Sep 18.

  PMID: 32945632 BACKGROUND

• Cosentini D, Grisanti S, Dalla Volta A, Lagana M, Fiorentini C, Perotti P, Sigala S, Berruti A. Immunotherapy failure in adrenocortical cancer: where next? Endocr Connect. 2018 Dec;7(12):E5-E8. doi: 10.1530/EC-18-0398.

  PMID: 30400026 BACKGROUND

• Le Tourneau C, Hoimes C, Zarwan C, Wong DJ, Bauer S, Claus R, Wermke M, Hariharan S, von Heydebreck A, Kasturi V, Chand V, Gulley JL. Avelumab in patients with previously treated metastatic adrenocortical carcinoma: phase 1b results from the JAVELIN solid tumor trial. J Immunother Cancer. 2018 Oct 22;6(1):111. doi: 10.1186/s40425-018-0424-9.

  PMID: 30348224 BACKGROUND

• Klein O, Senko C, Carlino MS, Markman B, Jackett L, Gao B, Lum C, Kee D, Behren A, Palmer J, Cebon J. Combination immunotherapy with ipilimumab and nivolumab in patients with advanced adrenocortical carcinoma: a subgroup analysis of CA209-538. Oncoimmunology. 2021 Apr 12;10(1):1908771. doi: 10.1080/2162402X.2021.1908771.

  PMID: 33889439 BACKGROUND

• McGregor BA, Campbell MT, Xie W, Farah S, Bilen MA, Schmidt AL, Sonpavde GP, Kilbridge KL, Choudhury AD, Mortazavi A, Shah AY, Venkatesan AM, Bubley GJ, Siefker-Radtke AO, McKay RR, Choueiri TK. Results of a multicenter, phase 2 study of nivolumab and ipilimumab for patients with advanced rare genitourinary malignancies. Cancer. 2021 Mar 15;127(6):840-849. doi: 10.1002/cncr.33328. Epub 2020 Nov 20.

  PMID: 33216356 BACKGROUND

• Carneiro BA, Konda B, Costa RB, Costa RLB, Sagar V, Gursel DB, Kirschner LS, Chae YK, Abdulkadir SA, Rademaker A, Mahalingam D, Shah MH, Giles FJ. Nivolumab in Metastatic Adrenocortical Carcinoma: Results of a Phase 2 Trial. J Clin Endocrinol Metab. 2019 Dec 1;104(12):6193-6200. doi: 10.1210/jc.2019-00600.

  PMID: 31276163 BACKGROUND

• Bedrose S, Miller KC, Altameemi L, Ali MS, Nassar S, Garg N, Daher M, Eaton KD, Yorio JT, Daniel DB, Campbell M, Bible KC, Ryder M, Chintakuntlawar AV, Habra MA. Combined lenvatinib and pembrolizumab as salvage therapy in advanced adrenal cortical carcinoma. J Immunother Cancer. 2020 Jul;8(2):e001009. doi: 10.1136/jitc-2020-001009.

  PMID: 32737143 BACKGROUND

• Habra MA, Stephen B, Campbell M, Hess K, Tapia C, Xu M, Rodon Ahnert J, Jimenez C, Lee JE, Perrier ND, Boraddus RR, Pant S, Subbiah V, Hong DS, Zarifa A, Fu S, Karp DD, Meric-Bernstam F, Naing A. Phase II clinical trial of pembrolizumab efficacy and safety in advanced adrenocortical carcinoma. J Immunother Cancer. 2019 Sep 18;7(1):253. doi: 10.1186/s40425-019-0722-x.

  PMID: 31533818 BACKGROUND

• Naing A, Meric-Bernstam F, Stephen B, Karp DD, Hajjar J, Rodon Ahnert J, Piha-Paul SA, Colen RR, Jimenez C, Raghav KP, Ferrarotto R, Tu SM, Campbell M, Wang L, Sabir SH, Tapia C, Bernatchez C, Frumovitz M, Tannir N, Ravi V, Khan S, Painter JM, Abonofal A, Gong J, Alshawa A, McQuinn LM, Xu M, Ahmed S, Subbiah V, Hong DS, Pant S, Yap TA, Tsimberidou AM, Dumbrava EEI, Janku F, Fu S, Simon RM, Hess KR, Varadhachary GR, Habra MA. Phase 2 study of pembrolizumab in patients with advanced rare cancers. J Immunother Cancer. 2020 Mar;8(1):e000347. doi: 10.1136/jitc-2019-000347.

  PMID: 32188704 BACKGROUND

• Grisanti S, Cosentini D, Lagana M, Volta AD, Palumbo C, Massimo Tiberio GA, Sigala S, Berruti A. The long and winding road to effective immunotherapy in patients with adrenocortical carcinoma. Future Oncol. 2020 Dec;16(36):3017-3020. doi: 10.2217/fon-2020-0686. Epub 2020 Aug 28. No abstract available.

  PMID: 32857613 BACKGROUND

• Raj N, Zheng Y, Kelly V, Katz SS, Chou J, Do RKG, Capanu M, Zamarin D, Saltz LB, Ariyan CE, Untch BR, O'Reilly EM, Gopalan A, Berger MF, Olino K, Segal NH, Reidy-Lagunes DL. PD-1 Blockade in Advanced Adrenocortical Carcinoma. J Clin Oncol. 2020 Jan 1;38(1):71-80. doi: 10.1200/JCO.19.01586. Epub 2019 Oct 23.

  PMID: 31644329 BACKGROUND

• Cremaschi V, Abate A, Cosentini D, Grisanti S, Rossini E, Lagana M, Tamburello M, Turla A, Sigala S, Berruti A. Advances in adrenocortical carcinoma pharmacotherapy: what is the current state of the art? Expert Opin Pharmacother. 2022 Aug;23(12):1413-1424. doi: 10.1080/14656566.2022.2106128. Epub 2022 Aug 3.

  PMID: 35876101 BACKGROUND

• Fassnacht M, Assie G, Baudin E, Eisenhofer G, de la Fouchardiere C, Haak HR, de Krijger R, Porpiglia F, Terzolo M, Berruti A; ESMO Guidelines Committee. Electronic address: clinicalguidelines@esmo.org. Adrenocortical carcinomas and malignant phaeochromocytomas: ESMO-EURACAN Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2020 Nov;31(11):1476-1490. doi: 10.1016/j.annonc.2020.08.2099. Epub 2020 Aug 27. No abstract available.

  PMID: 32861807 BACKGROUND

• Berruti A, Baudin E, Gelderblom H, Haak HR, Porpiglia F, Fassnacht M, Pentheroudakis G; ESMO Guidelines Working Group. Adrenal cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2012 Oct;23 Suppl 7:vii131-8. doi: 10.1093/annonc/mds231. No abstract available.

  PMID: 22997446 BACKGROUND

MeSH Terms

Conditions

Adrenocortical Carcinoma

Interventions

cemiplimab

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Adrenal Cortex Neoplasms; Adrenal Gland Neoplasms; Endocrine Gland Neoplasms; Neoplasms by Site; Adrenal Cortex Diseases; Adrenal Gland Diseases; Endocrine System Diseases

Study Officials

• Alfredo Berruti, Prof, MD

  ASST Spedali Civili di Brescia and University of Brescia

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Aldo Roccaro, MD, PhD

CONTACT

00390303996851; clinicaltrialcenter@asst-spedalicivili.it

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof.

Study Record Dates

• First Submitted: July 16, 2025
• First Posted: July 25, 2025
• Study Start: September 18, 2025
• Primary Completion (Estimated): July 1, 2028
• Study Completion (Estimated): July 1, 2028
• Last Updated: October 6, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)