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

Endometrial Cancer Clinical Trial

— EndoMAP  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04486352
• Other study ID #: AFT-50
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: October 20, 2021
• Est. completion date: October 2026

Study information

• Verified date: December 2023
• Source: Alliance Foundation Trials, LLC.
• Contact: Quality Management and Compliance
• Phone: 617-732-8727
• Email: ClinicalTrials.Queries[@]alliancefoundationtrials.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

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

• Atezolizumab + Ipatasertib doublet

• Atezolizumab + Talazoparib doublet

• Atezolizumab + Trastuzumab emtansine (TDM-1) doublet

• Atezolizumab + Tiragolumab doublet

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 148
• Est. completion date: October 2026
• Est. primary completion date: October 1, 2025
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

Key Inclusion Criteria:

• 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

Key Exclusion Criteria:

• 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

• 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

• 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

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

Related Conditions & MeSH terms

• Endometrial Cancer
• Endometrial Neoplasms

Intervention

Drug:
• 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.
• Bevacizumab
Bevacizumab will be given to participants intravenously at a dosage of 10mg per participant kilogram every 2 weeks of the 28-day cycle.
• Ipatasertib
Ipatasertib will be given as an orally at a dosage of 400 mg once daily for 21 days of each 28-day cycle.
• Talazoparib
Talazoparib will be given in an orally at a dosage of 1 mg once daily for each day of the 28-day cycle.
• 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.
• Tiragolumab
Tiragolumab will be given to participants intravenously at a dosage of 840 mg on day 1 of each 28-day cycle.
• 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.
• Inavolisib
Inavolisib will be given in an orally at a dosage of 9 mg once daily for each day of the 28-day cycle.
• Letrozole
Letrozole will be given orally at a dosage of 2.5 mg once daily for each day of the 28-day cycle.
• Giredestrant
Giredestrant will be given orally at a dosage of 30 mg once daily for each day of the 28-day cycle.
• Abemaciclib
Giredestrant will be given orally at a dosage of 150 mg twice daily for each day of the 28-day cycle.

Locations

Country	Name	City	State
United States	Dana Farber Cancer Institute	Boston	Massachusetts
United States	Roswell Park	Buffalo	New York
United States	University of Chicago	Chicago	Illinois
United States	City of Hope Comprehensive Cancer Center	Duarte	California
United States	Duke University Cancer Center	Durham	North Carolina
United States	Englewood Health	Englewood	New Jersey
United States	Baptist Memorial Hospital	Memphis	Tennessee
United States	Mount Sinai Comprehensive Cancer Center	Miami Beach	Florida
United States	University of Minnesota	Minneapolis	Minnesota
United States	Atlantic Health Systems/Morristown Medical Center	Morristown	New Jersey
United States	Weill Cornell Medicine	New York	New York
United States	University of Oklahoma Health Stephenson Cancer Center	Oklahoma City	Oklahoma
United States	Nebraska Methodist Hospital	Omaha	Nebraska
United States	University of Pittsburgh Medical Center	Pittsburgh	Pennsylvania
United States	Providence Portland Cancer Institute	Portland	Oregon
United States	Lifespan - Rhode Island Hospital	Providence	Rhode Island
United States	Washington University School of Medicine Siteman Cancer Center	Saint Louis	Missouri
United States	UCSF Helen Diller Family Comprehensive Cancer Center	San Francisco	California
United States	Medstar Georgetown Cancer Institute	Washington	District of Columbia
United States	University of Kansas Cancer Center	Westwood	Kansas

Sponsors (5)

Lead Sponsor	Collaborator
Alliance Foundation Trials, LLC.	Eli Lilly and Company, Foundation Medicine, Genentech, Inc., Pfizer

Country where clinical trial is conducted

United States, 

References & Publications (16)

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. — View Citation

Cancer Genome Atlas Research Network; Kandoth C, Schultz N, Cherniack AD, Akbani R, Liu Y, Shen H, Robertson AG, Pashtan I, Shen R, Benz CC, Yau C, Laird PW, Ding L, Zhang W, Mills GB, Kucherlapati R, Mardis ER, Levine DA. Integrated genomic characterization of endometrial carcinoma. Nature. 2013 May 2;497(7447):67-73. doi: 10.1038/nature12113. Erratum In: Nature. 2013 Aug 8;500(7461):242. — View Citation

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. — View Citation

Correction: A First-in-Human Phase I Study of the ATP-Competitive AKT Inhibitor Ipatasertib Demonstrates Robust and Safe Targeting of AKT in Patients with Solid Tumors. Cancer Discov. 2018 Nov;8(11):1490. doi: 10.1158/2159-8290.CD-18-1114. No abstract available. — View Citation

Gockley AA, Kolin DL, Awtrey CS, Lindeman NI, Matulonis UA, Konstantinopoulos PA. Durable response in a woman with recurrent low-grade endometrioid endometrial cancer and a germline BRCA2 mutation treated with a PARP inhibitor. Gynecol Oncol. 2018 Aug;150(2):219-226. doi: 10.1016/j.ygyno.2018.05.028. Epub 2018 Jun 22. — View Citation

Jiao S, Xia W, Yamaguchi H, Wei Y, Chen MK, Hsu JM, Hsu JL, Yu WH, Du Y, Lee HH, Li CW, Chou CK, Lim SO, Chang SS, Litton J, Arun B, Hortobagyi GN, Hung MC. PARP Inhibitor Upregulates PD-L1 Expression and Enhances Cancer-Associated Immunosuppression. Clin Cancer Res. 2017 Jul 15;23(14):3711-3720. doi: 10.1158/1078-0432.CCR-16-3215. Epub 2017 Feb 6. — View Citation

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 Blockade in Tumors with Mismatch-Repair Deficiency. N Engl J Med. 2015 Jun 25;372(26):2509-20. doi: 10.1056/NEJMoa1500596. Epub 2015 May 30. — View Citation

LoRusso PM. Inhibition of the PI3K/AKT/mTOR Pathway in Solid Tumors. J Clin Oncol. 2016 Nov 1;34(31):3803-3815. doi: 10.1200/JCO.2014.59.0018. Epub 2016 Sep 30. — View Citation

Miyasaka A, Oda K, Ikeda Y, Wada-Hiraike O, Kashiyama T, Enomoto A, Hosoya N, Koso T, Fukuda T, Inaba K, Sone K, Uehara Y, Kurikawa R, Nagasaka K, Matsumoto Y, Arimoto T, Nakagawa S, Kuramoto H, Miyagawa K, Yano T, Kawana K, Osuga Y, Fujii T. Anti-tumor activity of olaparib, a poly (ADP-ribose) polymerase (PARP) inhibitor, in cultured endometrial carcinoma cells. BMC Cancer. 2014 Mar 13;14:179. doi: 10.1186/1471-2407-14-179. — View Citation

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 bevacizumab versus sunitinib in patients with previously untreated metastatic renal cell carcinoma (IMmotion151): a multicentre, open-label, phase 3, randomised controlled trial. Lancet. 2019 Jun 15;393(10189):2404-2415. doi: 10.1016/S0140-6736(19)30723-8. Epub 2019 May 9. — View Citation

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 with locally advanced and metastatic urothelial carcinoma who have progressed following treatment with platinum-based chemotherapy: a single-arm, multicentre, phase 2 trial. Lancet. 2016 May 7;387(10031):1909-20. doi: 10.1016/S0140-6736(16)00561-4. Epub 2016 Mar 4. — View Citation

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. — View Citation

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. — View Citation

Strickland KC, Howitt BE, Shukla SA, Rodig S, Ritterhouse LL, Liu JF, Garber JE, Chowdhury D, Wu CJ, D'Andrea AD, Matulonis UA, Konstantinopoulos PA. Association and prognostic significance of BRCA1/2-mutation status with neoantigen load, number of tumor-infiltrating lymphocytes and expression of PD-1/PD-L1 in high grade serous ovarian cancer. Oncotarget. 2016 Mar 22;7(12):13587-98. doi: 10.18632/oncotarget.7277. — View Citation

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.2019.09.024. Epub 2019 Oct 15. — View Citation

Xue G, Zippelius A, Wicki A, Mandala M, Tang F, Massi D, Hemmings BA. Integrated Akt/PKB signaling in immunomodulation and its potential role in cancer immunotherapy. J Natl Cancer Inst. 2015 Jun 11;107(7):djv171. doi: 10.1093/jnci/djv171. Print 2015 Jul. — View Citation

* Note: There are 16 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Safety of each biomarker cohort: adverse events	AFT-50A Protocol: The incidence and severity of adverse events, with severity determined according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events, Version 5.0 (NCI CTCAE v5.0), as well as summaries of changes in clinically relevant laboratory test results, changes in vital signs, and study treatment exposures for each biomarker cohort	48 Months
Other	The safety of each biomarker cohort: Adverse Events	AFT-50B Protocol: The incidence and severity of adverse events, with severity determined according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events, Version 5.0 (NCI CTCAE v5.0). Summaries of changes in clinically relevant laboratory test results, changes in vital signs, and study treatment exposures for each biomarker cohort	48 Months
Other	Assess exploratory biomarkers in tumor tissue and peripheral blood, and their association with other molecular characteristics, disease status and/or participant response to study treatment	AFT-50A and AFT-50B Protocols: Association of exploratory biomarkers with clinical outcomes, including but not limited to molecular analysis of tumor tissue and peripheral blood, as well as cytokine/chemokine and cellular analysis of peripheral blood.	48 Months
Primary	Investigator-assessed overall response rate (ORR) of each biomarker cohort	AFT-50A Protocol: Overall response rate for each biomarker cohort is defined as the proportion of participants achieving a complete (CR) or partial (PR) response on two consecutive occasions at least 4 weeks apart, as determined by the investigator from AFT50A Protocol: Tumor assessments per RECIST v1.1.	48 Months
Primary	The proportion of participants in each biomarker cohort who remain alive and progression-free for at least 6 months	AFT-50B Protocol: Progression free survival rate at 6 months is defined as the proportion of participants who have not experienced disease progression or death from any cause at 6 months, as determined by the investigator according to RECIST v1.1	6 Months
Secondary	Relative proportion of participants in each biomarker cohort who remain progression-free for at least 6 months compared to that from historical control studies	AFT-50A Protocol: PFS rate at 6 months is defined as the proportion of participants who have not experienced disease progression or death from any cause at 6 months, as determined by the investigator according to RECIST v1.1	6 Months per cohort
Secondary	Investigator assessed disease-control rate of each biomarker cohort	AFT-50A Protocol: Disease-control rate is defined as the proportion of participants achieving either stable disease, complete response, or partial response.	48 Months
Secondary	Duration of response for participants in each biomarker cohort who achieve a complete or partial response.	AFT-50A Protocol: Duration of response is defined as the time from the first occurrence of a documented objective response to disease progression or death from any cause (whichever occurs first), as determined by the investigator according to RECIST v1.1.	48 Months
Secondary	Overall survival (OS) rates of participants in each biomarker cohort after 24 months	AFT-50A Protocol: 24-month overall survival rate is defined as the proportion of participants who have not experienced death from any cause at 24 months.	24 Months per cohort
Secondary	Investigator assessed disease-control rate of each biomarker cohort	AFT-50B Protocol: Disease control rate is defined as the proportion of participants achieving either stable disease, complete response, or partial response at any time.	48 Months
Secondary	Duration of response for participants in each biomarker cohort who achieve a confirmed response (complete or partial)	AFT-50B Protocol: Duration of response is defined as the time from the first occurrence of a documented objective response (complete or partial) to disease progression or death from any cause (whichever occurs first), as determined by the investigator according to RECIST v1.1	48 Months
Secondary	Overall survival rates of participants in each biomarker cohort	AFT-50B Protocol: 24-month overall survival rate is defined as the proportion of participants who have not experienced death from any cause at 24 months.	24 Months

External Links

•   CTCAE Version 5.0