A Study of Targeted Agents for Patients With Recurrent or Persistent Endometrial Cancer

Официальное название

A Phase IB/II Multi-Cohort Study of Targeted Agents and/or Immunotherapy With Atezolizumab for Patients With Recurrent or Persistent Endometrial Cancer

Обзор

This is a Phase IB/II multi-cohort study designed to evaluate the efficacy and safety of targeted agents with or without cancer immune checkpoint therapy with atezolizumab in participant with recurrent and/or persistent endometrial cancer. The main protocol provides a platform for genomic screening with homogeneous basic eligibility criteria in order to direct study participants into biomarker-matched study cohorts consisting of testing targeted agents.

Подробное описание

This is a Phase IB/II multi-cohort study designed to evaluate the efficacy and safety of targeted agents with or without cancer immune checkpoint therapy with atezolizumab in participants with recurrent and/or persistent endometrial cancer.

This biomarker-driven study provides a platform whereby participants with persistent/recurrent endometrial cancer will be placed into study cohorts evaluating targeted agents selected on the basis of the tumor's specific genomic profile. Prospective participants with persistent and/or recurrent endometrial cancer will be prescreened within 60 days of treatment assignment to have a tumor tissue sample submitted for next-generation sequencing (NGS) using FoundationOne® companion diagnostic (CDx) testing prior to entering screening. If a participant has FoundationOne® CDx testing within five years of enrollment, the previous tumor tissue may be re-analyzed for use in the study. Non-FMI NGS testing may be submitted if approved.

Depending on the cohort assignment per the tumor's biomarker profile, participants will be assigned to the AFT-50A Protocol (atezolizumab+targeted agent) or the AFT-50B Protocol (non-atezolizumab targeted agents). The current study cohorts are as follows:

AFT-50A Cohorts

* Atezolizumab + Bevacizumab doublet - Closed to Accrual * Atezolizumab + Ipatasertib doublet - Closed to Accrual * Atezolizumab + Talazoparib doublet * Atezolizumab + Trastuzumab emtansine (TDM-1) doublet - Closed to Accrual * Atezolizumab + Tiragolumab doublet - Closed to Accrual

AFT-50B Cohorts

* Inavolisib + Letrozole doublet * Giredestrant + Abemaciclib doublet

It is anticipated that approximately 20 participants will be enrolled in each study cohort in AFT-50A and 24 participants in each study cohort in AFT-50B, unless otherwise specified for a given cohort due to statistical considerations. Each study cohort will open/close independently of other study cohorts. Once a study cohort reaches the prespecified number of participants, it will be closed to further enrollment, unless an expansion phase is planned.

The study is structured to allow for additional cohorts to be added as the study progresses. These additional study cohorts may be proposed by investigators, but requires approval by the Steering Committee in order to be added to the protocol.

Вмешательства

• Препарат Atezolizumab - 28 Day Cycle
  Atezolizumab will be given to participants intravenously at a dosage of 1680 mg on day 1 of each 28-day cycle.
• Препарат Bevacizumab
  Bevacizumab will be given to participants intravenously at a dosage of 10mg per participant kilogram every 2 weeks of the 28-day cycle.
• Препарат Ipatasertib
  Ipatasertib will be given as an orally at a dosage of 400 mg once daily for 21 days of each 28-day cycle.
• Препарат Talazoparib
  Talazoparib will be given in an orally at a dosage of 1 mg once daily for each day of the 28-day cycle.
• Препарат Trastuzumab emtansine
  Trastuzumab emtansine be given to participants intravenously at a dosage of 3.6 mg per participant kilogram, on day 1 of each 21-day cycle.
• Препарат Tiragolumab
  Tiragolumab will be given to participants intravenously at a dosage of 840 mg on day 1 of each 28-day cycle.
• Препарат Atezolizumab - 21 Day Cycle
  Atezolizumab will be given to participants intravenously at a dosage of 1200 mg on day 1 of each 21-day cycle.
• Препарат Inavolisib
  Inavolisib will be given in an orally at a dosage of 9 mg once daily for each day of the 28-day cycle.
• Препарат Letrozole
  Letrozole will be given orally at a dosage of 2.5 mg once daily for each day of the 28-day cycle.
• Препарат Giredestrant
  Giredestrant will be given orally at a dosage of 30 mg once daily for each day of the 28-day cycle.

Первичные конечные точки

• Investigator-assessed overall response rate (ORR) of each biomarker cohort [Срок оценки: 48 Months]
• The proportion of participants in each biomarker cohort who remain alive and progression-free for at least 6 months [Срок оценки: 6 Months]

Вторичные конечные точки (7)

• Relative proportion of participants in each biomarker cohort who remain progression-free for at least 6 months compared to that from historical control studies [Срок оценки: 6 Months per cohort]
• Investigator assessed disease-control rate of each biomarker cohort [Срок оценки: 48 Months]
• Duration of response for participants in each biomarker cohort who achieve a complete or partial response. [Срок оценки: 48 Months]
• Overall survival (OS) rates of participants in each biomarker cohort after 24 months [Срок оценки: 24 Months per cohort]
• Investigator assessed disease-control rate of each biomarker cohort [Срок оценки: 48 Months]
• Duration of response for participants in each biomarker cohort who achieve a confirmed response (complete or partial) [Срок оценки: 48 Months]
• Overall survival rates of participants in each biomarker cohort [Срок оценки: 24 Months]

Критерии участия

Критерии включения

• Recurrent or persistent endometrial carcinoma which has progressed or recurred after at least 1, but no more than 2, prior lines of therapy. Prior hormonal therapies (e.g., tamoxifen, aromatase inhibitors) will not count toward the prior regimen limit. Chemotherapy given in conjunction with radiotherapy as a radiosensitizer will be counted as a systemic therapeutic regimen.
• Measurable disease per RECIST 1.1
• Availability of a representative tumor specimen that is suitable for determination of biomarker status via central testing (F1CDx) OR If a patient has a prior F1CDx report from 1 September 2019 or later, those NGS results can be used to determine biomarker status as long as the tumor tissue used in the report was obtained within 5 years prior to prescreening and appropriate signed consent is obtained from the patient.
• Life expectancy > 12 weeks
• Recovery from effects of recent radiotherapy, surgery, or chemotherapy

Критерии исключения

• Endometrial tumors with the following histologies: squamous carcinomas, sarcomas
• Other invasive malignancies within the last 5 years, except for non-melanoma skin cancer with no evidence of disease within the past 5 years AND localized breast cancer with previous adjuvant chemotherapy treatment for breast cancer completed > 5 years ago
• Synchronous primary invasive ovarian or cervical cancer
• Have an active or history of autoimmune disease or immune deficiency
• Have a history of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis based on a screening chest computed tomography (CT) scan
• Active tuberculosis
• Severe infections within 4 weeks
• Have received therapeutic oral or IV antibiotic medication within 2 weeks, except prophylactic antibiotic medication
• Have significant cardiovascular disease
• Are administered treatment with a live attenuated vaccine within 4 weeks, or anticipation of need for such a vaccine during the course of the study
• Have prior allogeneic bone marrow transplantation or solid organ transplant
• History of treatment with systemic immunostimulatory agents (including but not limited to interferons, interleukin-2) within 4 weeks or 5 half-lives of the drug, whichever is longer, prior to initiation of study treatment
• History of treatment with systemic immunosuppressive medications within 2 weeks except acute, low-dose, systemic immunosuppressant medications, corticosteroids for chronic obstructive pulmonary disease and asthma, or mineralocorticoids and low-dose corticosteroids for participants with orthostatic hypotension or adrenocortical insufficiency
• Have a history or clinical evidence of any untreated CNS disease, seizures not controlled with standard medical therapy, or history of cerebrovascular accident (stroke), transient ischemic attack or subarachnoid hemorrhage within 6 months

AFT-50A Specific Exclusion Criteria:

● Prior treatment with T-cell costimulating or immune checkpoint blockade therapies including, but not limited to, CD137 agonists, anti-PD-1, anti-PD-L1, and anti-CTLA-4 therapeutic antibodies

Note: Additional study cohort specific inclusion and exclusion criteria may apply based on cohort assignment.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 21 центр

• City of Hope Comprehensive Cancer Center — Duarte
• UCSF Helen Diller Family Comprehensive Cancer Center — San Francisco
• Medstar Georgetown Cancer Institute — Washington D.C.
• Mount Sinai Comprehensive Cancer Center — Miami Beach
• University of Chicago — Chicago
• University of Kansas Cancer Center — Westwood
• Maine Medical Center — Scarborough
• Dana Farber Cancer Institute — Boston
• … и ещё 13 центров

Публикации

• Aghajanian C, Sill MW, Darcy KM, Greer B, McMeekin DS, Rose PG, Rotmensch J, Barnes MN, Hanjani P, Leslie KK. Phase II trial of bevacizumab in recurrent or persistent endometrial cancer: a Gynecologic Oncology Group study. J Clin Oncol. 2011 Jun 1;29(16):2259-65. doi: 10.1200/JCO.2010.32.6397. Epub 2011 May 2. PMID 21537039
• Le DT, Uram JN, Wang H, Bartlett BR, Kemberling H, Eyring AD, Skora AD, Luber BS, Azad NS, Laheru D, Biedrzycki B, Donehower RC, Zaheer A, Fisher GA, Crocenzi TS, Lee JJ, Duffy SM, Goldberg RM, de la Chapelle A, Koshiji M, Bhaijee F, Huebner T, Hruban RH, Wood LD, Cuka N, Pardoll DM, Papadopoulos N, Kinzler KW, Zhou S, Cornish TC, Taube JM, Anders RA, Eshleman JR, Vogelstein B, Diaz LA Jr. PD-1 Bl PMID 26028255
• Rous J, Rems J, Cermak Z. [Extraction of peripherally located bronchial foreign bodies using a x-ray picture amplifier with a television loop]. Cesk Otolaryngol. 1975 Dec;24(6):335-41. No abstract available. Czech. PMID 1204078
• Rosenberg JE, Hoffman-Censits J, Powles T, van der Heijden MS, Balar AV, Necchi A, Dawson N, O'Donnell PH, Balmanoukian A, Loriot Y, Srinivas S, Retz MM, Grivas P, Joseph RW, Galsky MD, Fleming MT, Petrylak DP, Perez-Gracia JL, Burris HA, Castellano D, Canil C, Bellmunt J, Bajorin D, Nickles D, Bourgon R, Frampton GM, Cui N, Mariathasan S, Abidoye O, Fine GD, Dreicer R. Atezolizumab in patients wi PMID 26952546
• Schwartz LH, Seymour L, Litiere S, Ford R, Gwyther S, Mandrekar S, Shankar L, Bogaerts J, Chen A, Dancey J, Hayes W, Hodi FS, Hoekstra OS, Huang EP, Lin N, Liu Y, Therasse P, Wolchok JD, de Vries E. RECIST 1.1 - Standardisation and disease-specific adaptations: Perspectives from the RECIST Working Group. Eur J Cancer. 2016 Jul;62:138-45. doi: 10.1016/j.ejca.2016.03.082. Epub 2016 May 26. PMID 27237360
• Rini BI, Powles T, Atkins MB, Escudier B, McDermott DF, Suarez C, Bracarda S, Stadler WM, Donskov F, Lee JL, Hawkins R, Ravaud A, Alekseev B, Staehler M, Uemura M, De Giorgi U, Mellado B, Porta C, Melichar B, Gurney H, Bedke J, Choueiri TK, Parnis F, Khaznadar T, Thobhani A, Li S, Piault-Louis E, Frantz G, Huseni M, Schiff C, Green MC, Motzer RJ; IMmotion151 Study Group. Atezolizumab plus bevacizu PMID 31079938
• Colle R, Cohen R, Cochereau D, Duval A, Lascols O, Lopez-Trabada D, Afchain P, Trouilloud I, Parc Y, Lefevre JH, Flejou JF, Svrcek M, Andre T. Immunotherapy and patients treated for cancer with microsatellite instability. Bull Cancer. 2017 Jan;104(1):42-51. doi: 10.1016/j.bulcan.2016.11.006. Epub 2016 Dec 13. PMID 27979364
• Westin SN, Sill MW, Coleman RL, Waggoner S, Moore KN, Mathews CA, Martin LP, Modesitt SC, Lee S, Ju Z, Mills GB, Schilder RJ, Fracasso PM, Birrer MJ, Aghajanian C. Safety lead-in of the MEK inhibitor trametinib in combination with GSK2141795, an AKT inhibitor, in patients with recurrent endometrial cancer: An NRG Oncology/GOG study. Gynecol Oncol. 2019 Dec;155(3):420-428. doi: 10.1016/j.ygyno.2019 PMID 31623857

Идентификаторы

NCT: NCT04486352 · AFT-50

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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