RaPiDS- A Phase 2 Study of Anti-PD-1 Independently or in Combination With Anti-CTLA-4 in Second-Line Cervical Cancer

NCT03894215 | Terminated Phase 2 FDA Drug

• 1 other identifier: C-750-01/GOG-3028
• Study Type: interventional
• Target: 211
• Locations: 7 countries
• Sites: 68

Brief Summary

This is a randomized, blinded, non-comparative, two-arm Phase 2 clinical trial to assess the efficacy and safety of AGEN2034 administered with placebo (Treatment Arm 1 - monotherapy) or with AGEN1884 (Treatment Arm 2- combination therapy) for treatment of patients with advanced cervical cancer who relapsed or progressed after receiving first-line platinum-based chemotherapy. The study is not intended to compare the efficacy of the 2 experimental arms. Rather, the efficacy of each arm will be evaluated against its relevant historical controls as appropriate.

Conditions

Cervical Cancer

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate

  To assess the Objective Response Rate (ORR) to the treatment of AGEN2034 (anti-PD-1) administered with placebo (Treatment Arm 1 - monotherapy), or with AGEN1884 (anti-CTLA4) (Treatment Arm 2 - combination therapy), defined as the binomial proportion of intent to treat (ITT) patients with best overall response (BOR) of complete response (CR) or partial response (PR), in women with recurrent/persistent/metastatic cervical cancer who have progressed following first-line therapy. BOR will be determined by the Independent Radiology Review Committee (IRRC), according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1).

  48 months

Secondary Outcomes (16)

• Frequency, severity and duration of treatment-emergent AEs

  48 months

• DOR per RECIST 1.1

  48 months

• Time to Confirmed Progression

  48 months

• Immunogenicity of AGEN2034

  48 months

• Maximum observed drug concentration at steady state (Cmax-ss)

  48 months

Study Arms (2)

AGEN2034 + Placebo

EXPERIMENTAL

AGEN2034 administered with placebo monotherapy: approximately 100 patients.

Drug: AGEN2034

AGEN2034 + AGEN1884

EXPERIMENTAL

AGEN2034 administered in combination with AGEN1884 (combination therapy): approximately 100 patients.

Drug: AGEN2034; Drug: AGEN1884

Interventions

AGEN2034 DRUG

PD-1 antibody

AGEN2034 + AGEN1884; AGEN2034 + Placebo

AGEN1884 DRUG

CTLA-4 antibody

AGEN2034 + AGEN1884

Eligibility Criteria

• Age: 18 Years+
• Gender Eligibility Details: Only female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Voluntarily agree to participate by giving written informed consent. (Participation in pharmacogenomics testing is optional).
• Be ≥18 years of age.
• Diagnosis:
• Have (1) a histologically or cytologically confirmed diagnosis of squamous-cell carcinoma, adenosquamous carcinoma, or adenocarcinoma of the cervix, and (2) metastatic, locally advanced, and/or unresectable disease at the time of enrollment. Histologic confirmation of the original primary tumor is required via pathology report.
• Note: The following cervical tumors are not eligible: minimal deviation/adenoma malignum, gastric type adenocarcinoma, clear cell carcinoma, and mesonephric carcinoma.
• Has cervical cancer and has relapsed after a platinum- based treatment (first line) regimen for advanced (recurrent, unresectable, or metastatic) disease.
• Measurable Disease:
• a. Have measurable disease on imaging based on RECIST version 1.1 by Investigator assessments and independent central radiologic review.
• Note: Patients without centrally confirmed measurable disease at baseline will not be eligible for this trial.
• Note: Patients must have at least 1 "target lesion" to be used to assess response, as defined by RECIST version 1.1. Tumors within a previously irradiated field will be designated as "non-target" lesions unless progression is documented, or a biopsy is obtained to confirm persistence at least 90 days following completion of radiation therapy.
• Have a life expectancy of at least 3 months and an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Have adequate organ function as indicated by the following laboratory values:
• Adequate hematological function defined by absolute neutrophil count (ANC) \> 1.5 x 10\^9/L, platelet count \> 100 x 10\^9/L, and hemoglobin \>8 g/dL (without transfusions within 1 week of first dose).
• Adequate hepatic function based by a total bilirubin level ≤ 1.5 the institutional upper limit of normal (IULN), aspartate aminotransferase (AST) level ≤ 2.5 x IULN, alanine aminotransferase (ALT) level ≤ 2.5 x IULN, and alkaline phosphatase ≤ 2.5 IULN and albumin ≥3.0 mg/dL.
• Adequate renal function defined as creatinine ≤ 1.5 × upper limit of normal (ULN) OR measured or calculated creatinine clearance ≥ 40 mL/minute per Institutional standard. Assessment methods should be recorded.

You may not qualify if:

• The patient must be excluded from participating in the trial if the patient:
• Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigation device within 4 weeks of the first dose of treatment.
• Has an inadequate washout period prior to first dose of study drug defined as:
• Received systemic cytotoxic chemotherapy or biological therapy within 3 weeks before first dose,
• Received radiation therapy within 3 weeks before first dose, or
• Had major surgery within 4 weeks before first dose.
• Has received prior therapy with:
• Any antibody/drug targeting T-cell co-regulatory proteins (immune checkpoints) such as anti-PD-1, anti-PD-L1, or anti- cytotoxic T-lymphocyte antigen 4 (CTLA-4) antibodies
• More than 1 systemic treatment regimen for the advanced (recurrent, unresectable, or metastatic) cervical cancer for which the patient is considered for the study.
• Has persisting toxicity related to prior therapy of National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 (NCI-CTCAE) Grade \>1 severity.
• Note: Sensory neuropathy or alopecia of Grade ≤2 is acceptable.
• Is expected to require any other form of systemic or localized antineoplastic therapy while on trial (including maintenance therapy with another agent, radiation therapy, and/or surgical resection).
• Has known severe hypersensitivity reactions to fully human monoclonal antibodies (NCI-CTCAE Grade ≥3), any history of anaphylaxis, or uncontrolled asthma.
• Has received systemic corticosteroid therapy ≤ 7 days prior to the first dose of trial treatment or receiving any other form of systemic immunosuppressive medication (corticosteroid use on study for management of immune-related adverse events (AE), and/or a premedication for IV contrast allergies/reactions is allowed). Patients who are receiving daily corticosteroid replacement therapy are an exception to this rule. Daily prednisone at doses of up to 5 mg or equivalent hydrocortisone dose are examples of permitted replacement therapy.
• Has a central nervous system (CNS) tumor, metastasis(es), and/or carcinomatous meningitis identified either on the baseline brain imaging obtained during the screening period OR identified prior to consent.

Sponsors & Collaborators

• Agenus Inc.: lead
• GOG Foundation: collaborator

Study Sites (68)

University of Alabama at Birmingham School of Medicine

Birmingham, Alabama, 35233-1802, United States

Location

University of South Alabama Mitchell Cancer Institute

Mobile, Alabama, 36604, United States

Location

Arizona Oncology - Biltmore Cancer Center

Phoenix, Arizona, 85016, United States

Location

Arizona Oncology - Tucson - Wilmot Road Location

Tucson, Arizona, 85711, United States

Location

University of California, San Diego (UCSD) - Moores Cancer Center

La Jolla, California, 92093, United States

Location

UCLA- Women's Health Clinical Research Unit (WHCRU)

Los Angeles, California, 90095, United States

Location

Gynecologic Oncology Associates

Newport, California, 92663, United States

Location

California Pacific Medical Center

San Francisco, California, 94115-1821, United States

Location

University of California, San Francisco Medical Center

San Francisco, California, 94158, United States

Location

Baptist MD Anderson Cancer Center

Jacksonville, Florida, 32207, United States

Location

Moffitt Cancer Center

Tampa, Florida, 33612, United States

Location

Northside Hospital

Atlanta, Georgia, 30342, United States

Location

St Joseph's Hospital

Savannah, Georgia, 31405-6015, United States

Location

Community Health Network - North Cancer Center

Indianapolis, Indiana, 46250, United States

Location

University of Kentucky Albert B. Chandler Hospital

Lexington, Kentucky, 40536, United States

Location

Ochsner Clinic Foundation

New Orleans, Louisiana, 70121, United States

Location

MD Anderson Cancer Center at Cooper

Camden, New Jersey, 08103, United States

Location

University of New Mexico Cancer Center

Albuquerque, New Mexico, 87102, United States

Location

Northwell Health Monter Cancer Center

Lake Success, New York, 11042, United States

Location

Laura and Isaac Perlmutter Cancer Center at NYU Langone

New York, New York, 10016, United States

Location

SUNY Upstate Medical University

Syracuse, New York, 13210, United States

Location

Albert Einstein College of Medicine

The Bronx, New York, 10461, United States

Location

Levine Cancer Institute

Charlotte, North Carolina, 28204, United States

Location

FirstHealth Outpatient Cancer Center

Pinehurst, North Carolina, 28374, United States

Location

MetroHealth Medical Center

Cleveland, Ohio, 44109, United States

Location

The Ohio State University Wexner Medical Center

Columbus, Ohio, 43210, United States

Location

Columbus NCORP

Columbus, Ohio, 43215, United States

Location

Stephenson Cancer Center

Oklahoma City, Oklahoma, 73104-5418, United States

Location

Oklahoma Cancer Specialists and Research Institute, LLC

Tulsa, Oklahoma, 74146, United States

Location

Willamette Valley Cancer Institute

Eugene, Oregon, 97401, United States

Location

Northwest Cancer Specialists, P.C.

Portland, Oregon, 97227, United States

Location

Penn Medicine - Jordan Center for Gynecologic Cancer

Philadelphia, Pennsylvania, 19104-5127, United States

Location

WellSpan Gynecologic Oncology

York, Pennsylvania, 17403, United States

Location

Women & Infants Hospital of Rhode Island

Providence, Rhode Island, 02905, United States

Location

Texas Oncology Surgical Specialists - Austin Central

Austin, Texas, 78745, United States

Location

Texas Oncology - Bedford

Bedford, Texas, 76022, United States

Location

Texas Oncology - Dallas - Presbyterian Cancer Center

Dallas, Texas, 75231, United States

Location

The University of Texas Southwestern Medical Center

Dallas, Texas, 75390, United States

Location

Texas Oncology - Fort Worth Cancer Center

Fort Worth, Texas, 76104, United States

Location

Texas Oncology - San Antonio Medical Center

San Antonio, Texas, 78240, United States

Location

Texas Oncology - The Woodlands

The Woodlands, Texas, 77380, United States

Location

Texas Oncology

Tyler, Texas, 75702, United States

Location

CRIO - Centro Regional Integrado de Oncologia

Fortaleza, Ceará, 60336-045, Brazil

Location

Hospital Santa Rita

Vitória, Espírito Santo, 29043-260, Brazil

Location

IMIP - Instituto de Medicina Integral Prof. Fernando Figueira

Recife, Pernambuco, 50070-902, Brazil

Location

ONCOSITE/Hospital de Caridade de Ijuí

Ijuí, Rio Grande do Sul, 98700-000, Brazil

Location

Hospital Mãe de Deus

Porto Alegre, Rio Grande do Sul, 90110-270, Brazil

Location

CECOR - Centro Oncológico de Roraima

Boa Vista, Roraima, 69304-015, Brazil

Location

Hospital de Câncer de Barretos

Barretos, São Paulo, 14784-400, Brazil

Location

INCA - Instituto Nacional de Câncer

Rio de Janeiro, 20231-050, Brazil

Location

Instituto do Câncer do Estado de São Paulo

São Paulo, 01246-000, Brazil

Location

Perola Centro de Pesquisa em Oncologia

São Paulo, 01317-001, Brazil

Location

Hospital Amaral Carvalho

São Paulo, 17210-120, Brazil

Location

Fundação Antonio Prudente/AC Camargo Cancer Center

São Paulo, 9015-010, Brazil

Location

COI Centro Oncológico Internacional S.A.P.I. de C.V.

Mexico City, Mexico City, 04700, Mexico

Location

Christus Muguerza Hospital Vidriera

Monterrey, Nuevo León, 64570, Mexico

Location

Oaxaca Site Management Organization (OSMO)

Oaxaca City, 68000, Mexico

Location

Cancerologia De Queretaro

Querétaro, 76090, Mexico

Location

Clinica MonteSur, Centro de Investigación Clínica Montesur RCI -259

Lima Lima, 15023, Peru

Location

Seoul National University

Seoul, 03080, South Korea

Location

Gangnam Severence Hospital

Seoul, 06273, South Korea

Location

Samsung Medical Center

Seoul, South Korea

Location

Taichung Veterans General Hospital

Taichung, 40705, Taiwan

Location

Mackay Memorial Hospital Taipei Branch

Taipei, 10449, Taiwan

Location

Taipei Veterans General Hospital

Taipei, 11217, Taiwan

Location

Koo Foundation Sun Yat-Sen Cancer Center

Taipei, 11259, Taiwan

Location

King Chulalongkorn Memorial Hospital, Chulalongkorn University

Bangkok, 10330, Thailand

Location

Ramathibodi Hospital, Mahidol University

Bangkok, 10400, Thailand

Location

Related Publications (46)

• Allie SR, Zhang W, Fuse S, Usherwood EJ. Programmed death 1 regulates development of central memory CD8 T cells after acute viral infection. J Immunol. 2011 Jun 1;186(11):6280-6. doi: 10.4049/jimmunol.1003870. Epub 2011 Apr 27.

  PMID: 21525385 RESULT

• Antonia S, Goldberg SB, Balmanoukian A, Chaft JE, Sanborn RE, Gupta A, Narwal R, Steele K, Gu Y, Karakunnel JJ, Rizvi NA. Safety and antitumour activity of durvalumab plus tremelimumab in non-small cell lung cancer: a multicentre, phase 1b study. Lancet Oncol. 2016 Mar;17(3):299-308. doi: 10.1016/S1470-2045(15)00544-6. Epub 2016 Feb 6.

  PMID: 26858122 RESULT

• Antonia SJ, Lopez-Martin JA, Bendell J, Ott PA, Taylor M, Eder JP, Jager D, Pietanza MC, Le DT, de Braud F, Morse MA, Ascierto PA, Horn L, Amin A, Pillai RN, Evans J, Chau I, Bono P, Atmaca A, Sharma P, Harbison CT, Lin CS, Christensen O, Calvo E. Nivolumab alone and nivolumab plus ipilimumab in recurrent small-cell lung cancer (CheckMate 032): a multicentre, open-label, phase 1/2 trial. Lancet Oncol. 2016 Jul;17(7):883-895. doi: 10.1016/S1470-2045(16)30098-5. Epub 2016 Jun 4.

  PMID: 27269741 RESULT

• Barber DL, Wherry EJ, Masopust D, Zhu B, Allison JP, Sharpe AH, Freeman GJ, Ahmed R. Restoring function in exhausted CD8 T cells during chronic viral infection. Nature. 2006 Feb 9;439(7077):682-7. doi: 10.1038/nature04444. Epub 2005 Dec 28.

  PMID: 16382236 RESULT

• Borcoman E, Le Tourneau C. Pembrolizumab in cervical cancer: latest evidence and clinical usefulness. Ther Adv Med Oncol. 2017 Jun;9(6):431-439. doi: 10.1177/1758834017708742. Epub 2017 May 8.

  PMID: 28607581 RESULT

• Boutros C, Tarhini A, Routier E, Lambotte O, Ladurie FL, Carbonnel F, Izzeddine H, Marabelle A, Champiat S, Berdelou A, Lanoy E, Texier M, Libenciuc C, Eggermont AM, Soria JC, Mateus C, Robert C. Safety profiles of anti-CTLA-4 and anti-PD-1 antibodies alone and in combination. Nat Rev Clin Oncol. 2016 Aug;13(8):473-86. doi: 10.1038/nrclinonc.2016.58. Epub 2016 May 4.

  PMID: 27141885 RESULT

• Bristol-Myers Squibb USA, 2017a. Opdivo® (nivolumab) package insert,

  RESULT

• Bristol-Myers Squibb USA, 2017b. Yervoy® (ipilimumab) package insert,

  RESULT

• Buchbinder EI, Desai A. CTLA-4 and PD-1 Pathways: Similarities, Differences, and Implications of Their Inhibition. Am J Clin Oncol. 2016 Feb;39(1):98-106. doi: 10.1097/COC.0000000000000239.

  PMID: 26558876 RESULT

• Bulliard Y, Jolicoeur R, Windman M, Rue SM, Ettenberg S, Knee DA, Wilson NS, Dranoff G, Brogdon JL. Activating Fc gamma receptors contribute to the antitumor activities of immunoregulatory receptor-targeting antibodies. J Exp Med. 2013 Aug 26;210(9):1685-93. doi: 10.1084/jem.20130573. Epub 2013 Jul 29.

  PMID: 23897982 RESULT

• Callahan MK, Wolchok JD, Allison JP. Anti-CTLA-4 antibody therapy: immune monitoring during clinical development of a novel immunotherapy. Semin Oncol. 2010 Oct;37(5):473-84. doi: 10.1053/j.seminoncol.2010.09.001.

  PMID: 21074063 RESULT

• Camacho LH. CTLA-4 blockade with ipilimumab: biology, safety, efficacy, and future considerations. Cancer Med. 2015 May;4(5):661-72. doi: 10.1002/cam4.371. Epub 2015 Jan 25.

  PMID: 25619164 RESULT

• Carbone DP, Reck M, Paz-Ares L, Creelan B, Horn L, Steins M, Felip E, van den Heuvel MM, Ciuleanu TE, Badin F, Ready N, Hiltermann TJN, Nair S, Juergens R, Peters S, Minenza E, Wrangle JM, Rodriguez-Abreu D, Borghaei H, Blumenschein GR Jr, Villaruz LC, Havel L, Krejci J, Corral Jaime J, Chang H, Geese WJ, Bhagavatheeswaran P, Chen AC, Socinski MA; CheckMate 026 Investigators. First-Line Nivolumab in Stage IV or Recurrent Non-Small-Cell Lung Cancer. N Engl J Med. 2017 Jun 22;376(25):2415-2426. doi: 10.1056/NEJMoa1613493.

  PMID: 28636851 RESULT

• Carlino, M.S. et al., 2017. KEYNOTE-029: Efficacy and safety of pembrolizumab (pembro) plus ipilimumab (ipi) for advanced melanoma. In ASCO Annual Meeting. Chicago.

  RESULT

• Chand D, Savistky D, Gonzalez A,, et al. [Abstract]. J Immunother Cancer. 2017;5(Suppl2):P312.

  RESULT

• Chemnitz JM, Parry RV, Nichols KE, June CH, Riley JL. SHP-1 and SHP-2 associate with immunoreceptor tyrosine-based switch motif of programmed death 1 upon primary human T cell stimulation, but only receptor ligation prevents T cell activation. J Immunol. 2004 Jul 15;173(2):945-54. doi: 10.4049/jimmunol.173.2.945.

  PMID: 15240681 RESULT

• Chung CH. Managing premedications and the risk for reactions to infusional monoclonal antibody therapy. Oncologist. 2008 Jun;13(6):725-32. doi: 10.1634/theoncologist.2008-0012.

  PMID: 18586928 RESULT

• Chung HC, Schellens JHM, Delord JP, et al. 2018. Pembrolizumab treatment of advanced cervical cancer: Updated results from the phase 2 KEYNOTE-158 study. [ASCO abstract 5522]. J Clin Oncol. 36(15 suppl):5522.

  RESULT

• Das R, Verma R, Sznol M, Boddupalli CS, Gettinger SN, Kluger H, Callahan M, Wolchok JD, Halaban R, Dhodapkar MV, Dhodapkar KM. Combination therapy with anti-CTLA-4 and anti-PD-1 leads to distinct immunologic changes in vivo. J Immunol. 2015 Feb 1;194(3):950-9. doi: 10.4049/jimmunol.1401686. Epub 2014 Dec 24.

  PMID: 25539810 RESULT

• Disis ML. Immune regulation of cancer. J Clin Oncol. 2010 Oct 10;28(29):4531-8. doi: 10.1200/JCO.2009.27.2146. Epub 2010 Jun 1.

  PMID: 20516428 RESULT

• Drescher, C., Moore, M.N., Liu, J., O'Malley, D.M., Wang, E.W., Wang, J.S-Z., Subbish, V., et al. Phase 1/2, Open-Label, Multiple Ascending Dose Trial of AGEN2034, an Anti-PD-1 Monoclonal Antibody, in Advanced Solid Malignancies: Results of Dose Escalation in Advanced Cancer and Expansion Cohorts in Subjects With Relapsed/Refractory Cervical Cancer. Poster presented at European Society for Medical Oncology. Poster presented at ESMO 2018 Congress; 19 - 23 Oct 2018; Munich, Germany; Poster 1158P. Ann Oncol 2018 Oct; 29(Suppl 8).

  RESULT

• Eggermont AM, Chiarion-Sileni V, Grob JJ, Dummer R, Wolchok JD, Schmidt H, Hamid O, Robert C, Ascierto PA, Richards JM, Lebbe C, Ferraresi V, Smylie M, Weber JS, Maio M, Bastholt L, Mortier L, Thomas L, Tahir S, Hauschild A, Hassel JC, Hodi FS, Taitt C, de Pril V, de Schaetzen G, Suciu S, Testori A. Prolonged Survival in Stage III Melanoma with Ipilimumab Adjuvant Therapy. N Engl J Med. 2016 Nov 10;375(19):1845-1855. doi: 10.1056/NEJMoa1611299. Epub 2016 Oct 7.

  PMID: 27717298 RESULT

• Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, Dancey J, Arbuck S, Gwyther S, Mooney M, Rubinstein L, Shankar L, Dodd L, Kaplan R, Lacombe D, Verweij J. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009 Jan;45(2):228-47. doi: 10.1016/j.ejca.2008.10.026.

  PMID: 19097774 RESULT

• Food and Drug Administration. 2018. FDA approves pembrolizumab for advanced cervical cancer with disease progression during or after chemotherapy. https://www.fda.gov/drugs/informationondrugs/approveddrugs/ucm610572.htm. Accessed 14 January 2019.

  RESULT

• Frenel, J.-S. et al., 2017. Pembrolizumab in patients with advanced cervical squamous cell cancer: Preliminary results from the phase Ib KEYNOTE-028 study. Journal of Clinical Oncology, 34(suppl; abstr 5515).

  RESULT

• Goldman, J.W. et al., 2017. Nivolumab (N) plus ipilimumab (I) as first-line (1L) treatment for advanced (adv) NSCLC: 2-yr OS and long-term outcomes from CheckMate 012. In ASCO Annual Meeting. Chicago.

  RESULT

• Gombos RB, Gonzalez A, Manrique M, Chand D, Savitsky D, Morin B, Breous-Nystrom E, Dupont C, Ward RA, Mundt C, Duckless B, Tang H, Findeis MA, Schuster A, Waight JD, Underwood D, Clarke C, Ritter G, Merghoub T, Schaer D, Wolchok JD, van Dijk M, Buell JS, Cuillerot JM, Stein R, Drouin EE, Wilson NS. Toxicological and pharmacological assessment of AGEN1884, a novel human IgG1 anti-CTLA-4 antibody. PLoS One. 2018 Apr 4;13(4):e0191926. doi: 10.1371/journal.pone.0191926. eCollection 2018.

  PMID: 29617360 RESULT

• Goodman AM, Kato S, Bazhenova L, Patel SP, Frampton GM, Miller V, Stephens PJ, Daniels GA, Kurzrock R. Tumor Mutational Burden as an Independent Predictor of Response to Immunotherapy in Diverse Cancers. Mol Cancer Ther. 2017 Nov;16(11):2598-2608. doi: 10.1158/1535-7163.MCT-17-0386. Epub 2017 Aug 23.

  PMID: 28835386 RESULT

• Hammers HJ, Plimack ER, Infante JR, Rini BI, McDermott DF, Lewis LD, Voss MH, Sharma P, Pal SK, Razak ARA, Kollmannsberger C, Heng DYC, Spratlin J, McHenry MB, Amin A. Safety and Efficacy of Nivolumab in Combination With Ipilimumab in Metastatic Renal Cell Carcinoma: The CheckMate 016 Study. J Clin Oncol. 2017 Dec 1;35(34):3851-3858. doi: 10.1200/JCO.2016.72.1985. Epub 2017 Jul 5.

  PMID: 28678668 RESULT

• Hellmann, M.D. et al., 2016. CheckMate 012: safety and efficacy of first-line nivolumab and ipilimumab in advanced NSCLC. In ASCO Annual Meeting. Chicago: Proc Am Soc Clin Oncol.

  RESULT

• Hellmann MD, Rizvi NA, Goldman JW, Gettinger SN, Borghaei H, Brahmer JR, Ready NE, Gerber DE, Chow LQ, Juergens RA, Shepherd FA, Laurie SA, Geese WJ, Agrawal S, Young TC, Li X, Antonia SJ. Nivolumab plus ipilimumab as first-line treatment for advanced non-small-cell lung cancer (CheckMate 012): results of an open-label, phase 1, multicohort study. Lancet Oncol. 2017 Jan;18(1):31-41. doi: 10.1016/S1470-2045(16)30624-6. Epub 2016 Dec 5.

  PMID: 27932067 RESULT

• Hellmann MD, Callahan MK, Awad MM, Calvo E, Ascierto PA, Atmaca A, Rizvi NA, Hirsch FR, Selvaggi G, Szustakowski JD, Sasson A, Golhar R, Vitazka P, Chang H, Geese WJ, Antonia SJ. Tumor Mutational Burden and Efficacy of Nivolumab Monotherapy and in Combination with Ipilimumab in Small-Cell Lung Cancer. Cancer Cell. 2018 May 14;33(5):853-861.e4. doi: 10.1016/j.ccell.2018.04.001. Epub 2018 May 3.

  PMID: 29731394 RESULT

• Hellmann MD, Nathanson T, Rizvi H, Creelan BC, Sanchez-Vega F, Ahuja A, Ni A, Novik JB, Mangarin LMB, Abu-Akeel M, Liu C, Sauter JL, Rekhtman N, Chang E, Callahan MK, Chaft JE, Voss MH, Tenet M, Li XM, Covello K, Renninger A, Vitazka P, Geese WJ, Borghaei H, Rudin CM, Antonia SJ, Swanton C, Hammerbacher J, Merghoub T, McGranahan N, Snyder A, Wolchok JD. Genomic Features of Response to Combination Immunotherapy in Patients with Advanced Non-Small-Cell Lung Cancer. Cancer Cell. 2018 May 14;33(5):843-852.e4. doi: 10.1016/j.ccell.2018.03.018. Epub 2018 Apr 12.

  PMID: 29657128 RESULT

• Hollebecque, A. et al., 2017. An open-label, multicohort, phase I/II study of nivolumab in patients with virus-associated tumors (CheckMate 358): Efficacy and safety in recurrent or metastatic (R/M) cervical, vaginal, and vulvar cancers. Journal of Clinical Oncology, 35(suppl;abstr 5504).

  RESULT

• Huang G, Sun X, Liu D, Zhang Y, Zhang B, Xiao G, Li X, Gao X, Hu C, Wang M, Ren H, Qin S. The efficacy and safety of anti-PD-1/PD-L1 antibody therapy versus docetaxel for pretreated advanced NSCLC: a meta-analysis. Oncotarget. 2017 Dec 15;9(3):4239-4248. doi: 10.18632/oncotarget.23279. eCollection 2018 Jan 9.

  PMID: 29423118 RESULT

• Jia M, Feng W, Kang S, Zhang Y, Shen J, He J, Jiang L, Wang W, Guo Z, Peng G, Chen G, He J, Liang W. Evaluation of the efficacy and safety of anti-PD-1 and anti-PD-L1 antibody in the treatment of non-small cell lung cancer (NSCLC): a meta-analysis. J Thorac Dis. 2015 Mar;7(3):455-61. doi: 10.3978/j.issn.2072-1439.2015.02.06.

  PMID: 25922725 RESULT

• Keytruda [package insert]. Whitehouse Station, NJ; Merck and Co, Inc; 2018.

  RESULT

• Kumar V, Chaudhary N, Garg M, Floudas CS, Soni P, Chandra AB. Current Diagnosis and Management of Immune Related Adverse Events (irAEs) Induced by Immune Checkpoint Inhibitor Therapy. Front Pharmacol. 2017 Feb 8;8:49. doi: 10.3389/fphar.2017.00049. eCollection 2017.

  PMID: 28228726 RESULT

• Larkin J, Hodi FS, Wolchok JD. Combined Nivolumab and Ipilimumab or Monotherapy in Untreated Melanoma. N Engl J Med. 2015 Sep 24;373(13):1270-1. doi: 10.1056/NEJMc1509660. No abstract available.

  PMID: 26398076 RESULT

• Latchman Y, Wood CR, Chernova T, Chaudhary D, Borde M, Chernova I, Iwai Y, Long AJ, Brown JA, Nunes R, Greenfield EA, Bourque K, Boussiotis VA, Carter LL, Carreno BM, Malenkovich N, Nishimura H, Okazaki T, Honjo T, Sharpe AH, Freeman GJ. PD-L2 is a second ligand for PD-1 and inhibits T cell activation. Nat Immunol. 2001 Mar;2(3):261-8. doi: 10.1038/85330.

  PMID: 11224527 RESULT

• Long, G.V. et al., 2016. Pembrolizumab (pembro) plus ipilimumab (ipi) for advanced melanoma: Results of the KEYNOTE-029 expansion cohort. Journal of Clinical Oncology, 34(15_suppl), pp.9506-9506.

  RESULT

• Marabelle A, Kohrt H, Sagiv-Barfi I, Ajami B, Axtell RC, Zhou G, Rajapaksa R, Green MR, Torchia J, Brody J, Luong R, Rosenblum MD, Steinman L, Levitsky HI, Tse V, Levy R. Depleting tumor-specific Tregs at a single site eradicates disseminated tumors. J Clin Invest. 2013 Jun;123(6):2447-63. doi: 10.1172/JCI64859.

  PMID: 23728179 RESULT

• Mezache L, Paniccia B, Nyinawabera A, Nuovo GJ. Enhanced expression of PD L1 in cervical intraepithelial neoplasia and cervical cancers. Mod Pathol. 2015 Dec;28(12):1594-602. doi: 10.1038/modpathol.2015.108. Epub 2015 Sep 25.

  PMID: 26403783 RESULT

• Koh WJ, Greer BE, Abu-Rustum NR, Campos SM, Cho KR, Chon HS, Chu C, Cohn D, Crispens MA, Dizon DS, Dorigo O, Eifel PJ, Fisher CM, Frederick P, Gaffney DK, Han E, Higgins S, Huh WK, Lurain JR 3rd, Mariani A, Mutch D, Nagel C, Nekhlyudov L, Fader AN, Remmenga SW, Reynolds RK, Tillmanns T, Ueda S, Valea FA, Wyse E, Yashar CM, McMillian N, Scavone J. Vulvar Cancer, Version 1.2017, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw. 2017 Jan;15(1):92-120. doi: 10.6004/jnccn.2017.0008.

  PMID: 28040721 RESULT

• Oken MM, Creech RH, Tormey DC, Horton J, Davis TE, McFadden ET, Carbone PP. Toxicity and response criteria of the Eastern Cooperative Oncology Group. Am J Clin Oncol. 1982 Dec;5(6):649-55. No abstract available.

  PMID: 7165009 RESULT

• O'Malley DM, Randall LM, Jackson CG, Coleman RL, Hays JL, Moore KN, Naumann RW, Rocconi RP, Slomovitz BM, Tewari KS, Ancukiewicz M, Feliu WO, Monk BJ. RaPiDS (GOG-3028): randomized Phase II study of balstilimab alone or in combination with zalifrelimab in cervical cancer. Future Oncol. 2021 Sep;17(26):3433-3443. doi: 10.2217/fon-2021-0529. Epub 2021 Aug 19.

  PMID: 34409858 DERIVED

MeSH Terms

Conditions

Uterine Cervical Neoplasms

Interventions

balstilimab

Condition Hierarchy (Ancestors)

Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Uterine Cervical Diseases; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases

Study Officials

• Medical Director

  Agenus Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR
• Expanded Access: Yes

Study Record Dates

• First Submitted: March 19, 2019
• First Posted: March 28, 2019
• Study Start: June 1, 2019
• Primary Completion: March 26, 2025
• Study Completion: March 26, 2025
• Last Updated: March 27, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

PE (1); ME (4); BR (12); KR (3); TH (2); US (42); TW (4)