Pembrolizumab in Treating Patients With Rare Tumors That Cannot Be Removed by Surgery or Are Metastatic

NCT02721732 | Active Not Recruiting Phase 2 Results FDA Drug

• 2 other identifiers: 2015-0948NCI-2016-00545
• Study Type: interventional
• Target: 157
• Locations: 1 country
• Sites: 1

Brief Summary

This phase II trial studies how well pembrolizumab works in treating patients with rare tumors that cannot be removed by surgery or have spread to other parts of the body. Monoclonal antibodies, such as pembrolizumab, may block specific proteins found on white blood cells which may strengthen the immune system and control tumor growth.

Conditions

Carcinoma of Unknown Primary; Metastatic Adrenal Gland Pheochromocytoma; Metastatic Kidney Medullary Carcinoma; Metastatic Malignant Germ Cell Tumor; Metastatic Malignant Solid Neoplasm; Metastatic Paraganglioma; Metastatic Penile Carcinoma; Metastatic Skin Squamous Cell Carcinoma; Small Cell Carcinoma; Stage III Adrenal Cortex Carcinoma AJCC v7; Stage IV Adrenal Cortex Carcinoma AJCC v7; Stage IV Penile Cancer AJCC v7; Stage IV Renal Cell Cancer AJCC v7; Unresectable Adrenal Gland Pheochromocytoma; Unresectable Paraganglioma; Unresectable Solid Neoplasm; Vascular Neoplasm; Advanced Malignant Solid Neoplasm; Unresectable Skin Squamous Cell Carcinoma

Outcome Measures

Primary Outcomes (1)

• Non-progression Rate (NPR) at 27 Weeks by irRECIST

  Non-progression rate (NPR) at 27 weeks was defined as the percentage of efficacy evaluable patients who were alive and progression-free at 27 weeks as assessed by irRECIST Progression is defined using immune-related Response Evaluation Criteria in Solid Tumors (irRECIST), as an increase ≥ 20% (minimum 5 mm) in total measured tumor burden compared with nadir or progression of non-target lesions or new lesion

  At 27 weeks

Secondary Outcomes (8)

• Evaluation of Tumor Size (Objective Response by irRECIST) to PD-L1 Status (CPS ≥1)

  Baseline and every 9 weeks thereafter. After 6 months, every 12 weeks at the physician's discretion, if patient has had CR, PR, or SD > 27 weeks, an average of 4 years.

• Number of Patients Who Experienced Treatment-related Adverse Event (TRAE)

  First day of administration of study medication through 30 days following last dose, an average of 4 years.

• Objective Response Rate (ORR) Using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1

  Baseline and every 9 weeks thereafter. After 6 months, every 12 weeks at the physician's discretion, if patient has had CR, PR, or SD > 27 weeks, an average of 4 years.

• Clinical Benefit Rate (CBR) Using RECIST v1.1

  Baseline and every 9 weeks thereafter. After 6 months, every 12 weeks at the physician's discretion, if patient has had CR, PR, or SD > 27 weeks, an average of 4 years.

• Progression-free Survival (PFS) Using RECIST v1.1

  Baseline and every 9 weeks thereafter. After 6 months, every 12 weeks at the physician's discretion, if patient has had CR, PR, or SD > 27 weeks, an average of 4 years.

Study Arms (1)

Treatment (pembrolizumab)

EXPERIMENTAL

Patients receive pembrolizumab IV over 30 minutes on day 1. Treatment repeats every 21 days for up to 24 months in the absence of disease progression or toxicity. Patients with clinical response or disease stabilization may continue treatment for up to an additional 12 months.

Other: Laboratory Biomarker Analysis; Biological: Pembrolizumab; Other: Questionnaire Administration

Interventions

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (pembrolizumab)

Pembrolizumab BIOLOGICAL

Given IV

Also known as: Keytruda, Lambrolizumab, MK-3475, SCH 900475

Treatment (pembrolizumab)

Questionnaire Administration OTHER

Ancillary studies

Treatment (pembrolizumab)

Eligibility Criteria

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

You may qualify if:

• Be willing and able to provide written informed consent/assent for the trial
• Have measurable disease based on RECIST 1.1 or irRECIST; only cohort 9 and 10 can have evaluable disease (non-measurable lesions); tumor lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions; patients may have bone metastatic disease evaluable according to tumor evaluation criteria best suitable and accepted for the tumor type evaluated
• Have one of the following advanced (unresectable and/or metastatic) solid tumor indications that has progressed following standard therapies, where standard therapies are available:
• Squamous cell carcinoma of the skin
• Small cell malignancies of non-pulmonary origin
• Adrenocortical carcinoma
• Medullary renal cell carcinoma
• Carcinoma of unknown primary
• Penile carcinoma
• Vascular sarcoma
• Germ cell tumor
• Paraganglioma-pheochromocytoma
• Have failed prior treatment within 6 months of consent date
• Have biopsiable disease; subjects must have at least one lesion amenable to biopsy; tumor lesions used for biopsy should not be lesions used as target lesions; in cohort 9: paraganglioma-pheochromocytoma or cohort 10, where there is prominent bony disease, biopsies may not be possible due to the nature of the disease
• Be willing to provide archival tissue; if archival tissue is not available, or a newly obtained core or excisional biopsy of a tumor lesion will be obtained; newly-obtained is defined as a specimen obtained up to 6 weeks (42 days) prior to initiation of treatment on day 1; in cohort 9: paraganglioma-pheochromocytoma or cohort 10, where there is prominent bony disease, biopsies may not be possible due to the nature of the disease

You may not qualify if:

• Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment
• Has a known history of active TB (bacillus tuberculosis)
• Hypersensitivity to pembrolizumab or any of its excipients
• Has not recovered (i.e., =\< grade 1 or at baseline) from adverse events due to a previously administered agent; Note: subjects with =\< grade 2 neuropathy are an exception to this criterion and may qualify for the study; Note: if subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy
• Has a known additional malignancy that is progressing or requires active treatment; exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer, and diseases for which the treatment could reasonably include pembrolizumab and are not part of the excluded tumor type list or not eligible for the phase I trial
• Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis; subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment; this exception does not include carcinomatous meningitis which is excluded regardless of clinical stability
• Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs); replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment; immunosuppressive corticosteroid doses (\> 10 mg prednisone daily or equivalent) within 4 weeks prior to the first dose of pembrolizumab; Note: corticosteroids given within 24 hours of an imaging study for purposes of pre-medication in patients with hypersensitivity to radiologic contrast agents are allowed
• Has known history of, or any evidence of active, non-infectious pneumonitis
• Has an active infection requiring systemic therapy
• Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator
• Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial
• Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment
• Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent
• Has a known history of human immunodeficiency virus (HIV) (HIV 1/2 antibodies)
• Has known active hepatitis B (e.g., hepatitis B surface antigen \[HBsAg\] reactive) or hepatitis C (e.g., hepatitis C virus \[HCV\] ribonucleic acid \[RNA\] \[qualitative\] is detected)

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Publications (15)

• Chahla B, Stephen B, Song J, Balderrama-Brondani V, Yaylaci F, Campbell MT, Naing A, Habra MA. Phase 2 Study of Monotherapy with Pembrolizumab for Advanced Adrenocortical Carcinoma. J Immunother Precis Oncol. 2025 Oct 6;8(4):242-248. doi: 10.36401/JIPO-25-6. eCollection 2025 Nov.

  PMID: 41143139 DERIVED

• Nardo M, Braganca Xavier C, Stephen B, How JA, Moyers J, Subbiah V, Hong DS, Naing A. Pembrolizumab in Patients with Advanced Miscellaneous Rare Cancers: Results from a Phase 2 Basket Trial. J Immunother Precis Oncol. 2025 Apr 10;8(2):143-151. doi: 10.36401/JIPO-24-27. eCollection 2025 May.

  PMID: 40212844 DERIVED

• Nze C, Msaouel P, Derbala MH, Stephen B, Abonofal A, Meric-Bernstam F, Tannir NM, Naing A. A Phase II Clinical Trial of Pembrolizumab Efficacy and Safety in Advanced Renal Medullary Carcinoma. Cancers (Basel). 2023 Jul 27;15(15):3806. doi: 10.3390/cancers15153806.

  PMID: 37568622 DERIVED

• Mendoza TR, Hong DS, Peterson CB, Stephen B, Dumbrava E, Pant S, Tsimberidou AM, Yap TA, Sheshadri A, Altan M, George G, Castillo L, Rodriguez E, Gong J, Subbiah V, Janku F, Fu S, Piha-Paul SA, Ahnert JR, Karp DD, Cleeland C, Meric-Bernstam F, Naing A. Patient-reported symptom burden in patients with rare cancers receiving pembrolizumab in a phase II Clinical Trial. Sci Rep. 2022 Aug 23;12(1):14367. doi: 10.1038/s41598-022-16588-3.

  PMID: 35999229 DERIVED

• Raghav KP, Stephen B, Karp DD, Piha-Paul SA, Hong DS, Jain D, Chudy Onwugaje DO, Abonofal A, Willett AF, Overman M, Smaglo B, Huey RW, Meric-Bernstam F, Varadhachary GR, Naing A. Efficacy of pembrolizumab in patients with advanced cancer of unknown primary (CUP): a phase 2 non-randomized clinical trial. J Immunother Cancer. 2022 May;10(5):e004822. doi: 10.1136/jitc-2022-004822.

  PMID: 35618285 DERIVED

• Pant S, Moyers JT, Naing A. Letter to the editor from Pant et al. J Immunother Cancer. 2021 Nov;9(11):e003991. doi: 10.1136/jitc-2021-003991. No abstract available.

  PMID: 34725215 DERIVED

• Ferrarotto R, Sousa LG, Qing Y, Kaya D, Stephen B, Jain D, Bell D, Pant S, Tsimberidou AM, Janku F, Blumenschein G, Glisson BS, Ahnert JR, Piha-Paul SA, Lee JJ, Wong MK, Lu C, Meric-Bernstam F, Naing A. Pembrolizumab in Patients with Refractory Cutaneous Squamous Cell Carcinoma: A Phase II Trial. Adv Ther. 2021 Aug;38(8):4581-4591. doi: 10.1007/s12325-021-01807-6. Epub 2021 Jul 9.

  PMID: 34241781 DERIVED

• Hahn AW, Chahoud J, Campbell MT, Karp DD, Wang J, Stephen B, Tu SM, Pettaway CA, Naing A. Pembrolizumab for advanced penile cancer: a case series from a phase II basket trial. Invest New Drugs. 2021 Oct;39(5):1405-1410. doi: 10.1007/s10637-021-01100-x. Epub 2021 Mar 26.

  PMID: 33770291 DERIVED

• Tsimberidou AM, Vo HH, Subbiah V, Janku F, Piha-Paul S, Yilmaz B, Gong J, Naqvi MF, Tu SM, Campbell M, Meric-Bernstam F, Naing A. Pembrolizumab in Patients with Advanced Metastatic Germ Cell Tumors. Oncologist. 2021 Jul;26(7):558-e1098. doi: 10.1002/onco.13682. Epub 2021 Feb 12.

  PMID: 33491277 DERIVED

• Majd N, Waguespack SG, Janku F, Fu S, Penas-Prado M, Xu M, Alshawa A, Kamiya-Matsuoka C, Raza SM, McCutcheon IE, Naing A. Efficacy of pembrolizumab in patients with pituitary carcinoma: report of four cases from a phase II study. J Immunother Cancer. 2020 Dec;8(2):e001532. doi: 10.1136/jitc-2020-001532.

  PMID: 33427689 DERIVED

• How JA, Jazaeri A, Westin SN, Sood AK, Ramondetta LM, Xu M, Abonofal A, Karp DD, Subbiah V, Stephen B, Rodon JA, Yang F, Naing A. The clinical efficacy and safety of single-agent pembrolizumab in patients with recurrent granulosa cell tumors of the ovary: a case series from a phase II basket trial. Invest New Drugs. 2021 Jun;39(3):829-835. doi: 10.1007/s10637-020-01043-9. Epub 2021 Jan 7.

  PMID: 33415580 DERIVED

• Frumovitz M, Westin SN, Salvo G, Zarifa A, Xu M, Yap TA, Rodon AJ, Karp DD, Abonofal A, Jazaeri AA, Naing A. Phase II study of pembrolizumab efficacy and safety in women with recurrent small cell neuroendocrine carcinoma of the lower genital tract. Gynecol Oncol. 2020 Sep;158(3):570-575. doi: 10.1016/j.ygyno.2020.05.682. Epub 2020 Jun 11.

  PMID: 32534809 DERIVED

• Tapia C, Aung PP, Roy-Chowdhuri S, Xu M, Ouyang F, Alshawa A, Hajjar J, Singh G, Yang V, Castillo L, Le H, Murthy R, Stephen B, Hess KR, Wistuba I, Naing A. Decrease in tumor content assessed in biopsies is associated with improved treatment outcome response to pembrolizumab in patients with rare tumors. J Immunother Cancer. 2020 Apr;8(1):e000665. doi: 10.1136/jitc-2020-000665.

  PMID: 32303619 DERIVED

• 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 DERIVED

• 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 DERIVED

Related Links

• MD Anderson Cancer Center Website

MeSH Terms

Conditions

Neoplasms, Unknown Primary; Pheochromocytoma; Neoplasm Metastasis; Paraganglioma; Penile Neoplasms; Carcinoma, Small Cell; Adrenal Cortex Neoplasms; Carcinoma, Renal Cell; Vascular Neoplasms

Interventions

pembrolizumab

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Nerve Tissue; Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Penile Diseases; Male Urogenital Diseases; Carcinoma; Neoplasms, Glandular and Epithelial; Adrenal Gland Neoplasms; Endocrine Gland Neoplasms; Adrenal Cortex Diseases; Adrenal Gland Diseases; Endocrine System Diseases; Adenocarcinoma; Kidney Neoplasms; Urologic Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Kidney Diseases; Urologic Diseases; Soft Tissue Neoplasms; Vascular Diseases; Cardiovascular Diseases

Results Point of Contact

• Title: Dr. Aung Naing
• Organization: The University of Texas MD Anderson Cancer Center

anaing@mdanderson.org

(713) 563-3885

Study Officials

• Aung Naing

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 23, 2016
• First Posted: March 29, 2016
• Study Start: August 15, 2016
• Primary Completion (Estimated): December 31, 2028
• Study Completion (Estimated): December 31, 2028
• Last Updated: January 29, 2026
• Results First Posted: June 18, 2024

Record last verified: 2026-01

Locations

US (1)