M7824 in Subjects With HPV Associated Malignancies

Learn more about:
Related Clinical Trial
CRTE7A2-01 TCR-T Cell for HPV-16 Positive Advanced Cervical, Anal, or Head and Neck Cancers Assessment of Patients’ Quality of Sexual Life After Anal Cancer Treatment Neoadjuvant PD-1 Blockade Combined With Chemotherapy Followed by Concurrent Immunoradiotherapy for Locally Advanced Anal Canal Squamous Carcinoma Patients Pencil Beam Proton Therapy for Recurrences in Anal Cancer Patients Previously Treated With Radiotherapy (DACG 5) Hyperthermia Enhanced Re-irradiation of Loco-regional Recurrent Tumors Detecting HPV DNA in Anal and Cervical Cancers ANCA II – Quality of Life and Functional Outcome in Patients With Anal Cancer RTX-321 Monotherapy in Patients With HPV 16+ Tumors Anal Injury Screening for High Risk HPV M7824 in Subjects With HPV Associated Malignancies Multimodal Monitoring of Radiotherapy Response in Squamous Cell Cancer Avastin/[18-F]-5-fluorouracil PET/CT Imaging Feasibility Project Assessment of Health Related Quality of Life in Patients Treated for Rectal Cancer Octreotide in Preventing or Reducing Diarrhea in Patients Receiving Chemoradiotherapy for Anal or Rectal Cancer Combination Immunotherapy in Subjects With Advanced HPV Associated Malignancies Function Following Laser for Anal Intraepithelial Neoplasia (FLAN) A Message Framing Intervention for Increasing Parental Acceptance of Human Papillomavirus Vaccination Anal Sphincter Prosthesis in Treating Patients Who Are Undergoing Surgery for Anal or Rectal Cancer Phase 2 Study of ADXS11-001 in Subjects With Carcinoma of the Anorectal Canal Pilot Study to Determine the Safety and Efficacy of Gardasil Against the Human Papilloma Virus (HPV) in HIV-infected Men Assessment of Symptom-Related Cytokines in Lung and Gastrointestinal (GI) Cancer Patients Identification of Predictive Factors for Physiological Hypermetabolism of the Anal Canal in 18F-FDG PET / CT Early Rectal Cancer: Endoscopic Submucosal Dissection or Transanal Endoscopic Microsurgery? Drainage Seton With Flap Versus EAS Preserving Seton in Treatment of Transsphincteric Anal Fistula HPV-SAVE: 9-Valent HPV Vaccine for High-Grade Anal Dysplasia Radiation Dosimetry Study Comparing 2 Different Patient Setups in Anal/Rectal Cancer Patients Comparing Two Types of Swabs in Collecting Cell Samples for Anal Pap Tests and Human Papillomavirus Tests in Men Who Have Sex With Men The HPV-SAVE Study Team: HPV Screening and Vaccine Evaluation in Men Who Have Sex With Men High-Resolution Anoscopy Perceived Discomfort Study Infrared Coagulator Ablation or Observation in Preventing Anal Cancer in HIV-Positive Patients With Anal Neoplasia Image Fusion PET, CT and 3D-ultrasound Examinations Hybrid Capture 2 Human Papiloma Virus (HPV) High-Risk Anal DNA Test ART: Anal Squamous Cell Carcinoma: Investigation of Functional Imaging During chemoRadioTherapy Anal HPV Tests in Screening for Cell Changes in the Anus in Patients With HIV Molecular Genetic and Pathological Studies of Anal Tumors Intensity-Modulated Radiation Therapy, Fluorouracil, and Mitomycin C in Treating Patients With Invasive Anal Cancer Capecitabine, Oxaliplatin, and Radiation Therapy in Treating Patients With Stage II or Stage III Anal Cancer QOL & Functional Outcomes After Combined Modality Tx for Anal CA: Comparison of Conventional vs IMRT A Study of mDCF in Combination or Not With Atezolizumab in Advanced Squamous Cell Anal Carcinoma Chemotherapy Plus Radiation Therapy in Treating Patients With Stage II or Stage III Anal Cancer Infrared Coagulation in Preventing Anal Cancer in Patients With HIV Who Have Anal Neoplasia Combination Chemotherapy Plus Radiation Therapy in Treating Patients With Stage II or Stage III Anal Cancer Topical MTS-01 for Dermatitis During Radiation and Chemotherapy for Anal Cancer Radiochemotherapy +/- Durvalumab for Locally-advanced Anal Carcinoma. A Multicenter, Randomized, Phase II Trial of the German Anal Cancer Study Group Intrafractional Vaginal Dilation in Anal Cancer Patients Undergoing Pelvic Radiotherapy Screening for HIV-Associated Anal Cancer Combined Modality Therapy for Patients With With HIV and Stage I, Stage II, or Stage III Anal Cancer Cetuximab, Cisplatin, Fluorouracil, and Radiation Therapy in Treating Patients With Anal Cancer Study of IMRT Radiotherapy Concurrent Chemothrerapy for Anal Cancer A Prospective, Open-Label, Multi-center Comparison of Lymphoseek Identified Lymph Nodes and Clinically Identified Lymph Nodes of Subjects With Known Cancer of the Anus Prospective Observational Trial to Evaluate Quality of Life After Definitive Chemoradiation in Patients With Anal Cancer (LANACARE) Radiation Therapy Plus Fluorouracil With or Without Additional Chemotherapy in Treating Patients With Primary Anal Cancer Prospective Cohort on Quality of Sexual Life Among Men Who Have Sex With Men Treated for Anal Cancer With Concurrent Chemotherapy and Intensity-modulated Radiotherapy Trial To Test Safety And Efficacy Of Vaccination For Incurable HPV 16-Related Oropharyngeal, Cervical And Anal Cancer SGN-00101 in Preventing Anal Cancer in Patients With HIV Who Have Anal Neoplasia Anal Cancer Radiotherapy Study Radiation Therapy, Mitomycin, and Either Fluorouracil or Cisplatin in Treating Patients With Locally Advanced Anal Cancer Radiation Therapy, Cisplatin, Fluorouracil, and Cetuximab in Treating Patients With Locally Advanced Anal Cancer Individual Following in Anal Cancer With PET/CT Anal Cancer Screening Study The Prevent Anal Cancer Self-Swab Study Shared Decision Making With Anal Cancer Patients on Radiation Dose Predictive Value of FMISO-PET, FDG-PET-CT, DWI-MRI and DCE-MRI Scans for Patients With Anal Cancer Receiving Radiotherapy +/- Chemotherapy Quality of Life in Patients With Anal Cancer Functional Outcomes Following Anal Cancer Treatment Pembrolizumab in Refractory Metastatic Anal Cancer A Phase I/II Evaluation of ADXS11-001, Mitomycin, 5-fluorouracil (5-FU) and IMRT for Anal Cancer

Brief Title

M7824 in Subjects With HPV Associated Malignancies

Official Title

Phase II Trial of M7824 in Subjects With HPV Associated Malignancies

Brief Summary

      Background:

      In the United States, each year there are more than 30,000 cases of human papillomavirus
      (HPV) associated cancers. Some of these cancers are often incurable and are not improved by
      standard therapies. Researchers want to see if a new drug M7824, which targets and blocks a
      pathway that prevents the immune system from effectively fighting the cancer can shrink
      tumors in people with some HPV cancers.

      Objectives:

      To see if the drug M7824 causes tumors to shrink.

      Eligibility:

      Adults age 18 and older who have a cancer associated with HPV infection.

      Design:

      Participants will be screened with medical history and physical exam. They will review their
      symptoms and how they perform normal activities. They will have body scans. They will give
      blood and urine samples. They will have a sample of their tumor tissue taken if one is not
      available.

      Participants will have an electrocardiogram to evaluate their heart. Then they will get the
      study drug through a thin tube in an arm vein.

      Participants will get the drug every 2 weeks for 26 times (1 year). This is 1 course.

      After the course, participants will be monitored but will not take the study drug. If their
      condition gets worse, they will start another course with the drug. This process can be
      repeated as many times as needed.

      Treatment will stop if the participant has bad side effects or the drug stops working.

      Throughout the study, participants will repeat some or all the screening tests.

      After participants stop taking the drug, they will have a follow-up visit and repeat some
      screening tests. They will get periodic follow-up phone calls.

      ...
    

Detailed Description

      Background:

        -  Metastatic or refractory/recurrent HPV associated malignancies (cervical, anal,
           oropharyngeal cancers etc.) are often incurable and poorly palliated by standard
           therapies.

             -  TGF R1 pathway signaling and overexpression are significantly associated with HPV+
                cancers.

             -  PD-1 inhibitors have produced a 12-20% response rate for these diseases

             -  M7824 is a novel bifunctional fusion protein composed of monoclonal antibodies
                against human PD- L1 and soluble extracellular domain of human TGF- receptor II
                (TGF- RII), which functions as a TGF- "trap."

             -  Early data from a small cohort of patients with HPV associated malignancies in a
                phase I trial of M7824 has shown promising activity (NCT02517398). As of May 30,
                2017, 4 of 9 patients (44%) with HPV associated malignancies have had preliminary
                evidence of clinical benefit including:

        -  Patient with metastatic cervical cancer with a 25% reduction in her disease at 3 months

        -  Patient with metastatic P16+ head and neck cancer with an unconfirmed partial response
           (PR) at 6 weeks

        -  Patient with metastatic anal cancer with a durable PR ongoing 9 months after starting
           treatment

        -  Patient with metastatic cervical cancer with a durable complete response (CR) ongoing 15
           months after starting treatment.

        -  Notably, the P16+ head and neck cancer patient with unconfirmed PR, anal cancer patient
           with durable PR and cervical cancer patient with durable CR all have HPV+ disease.

             -  Immune related adverse events with M7824 in the phase I trial to date have been on
                par with other PD-1/PD-L1 inhibitors, suggesting a manageable safety profile.

             -  EMD Serono has an ongoing expansion cohort evaluating M7824 in patients with HNSCC
                as well as in cervical cancer excluding neuroendocrine cervical cancer.

      Objective:

      -To determine the objective response rate (ORR) according to the Response Evaluation Criteria
      in Solid Tumors (RECIST 1.1) in subjects with recurrent or metastatic HPV associated
      malignancies.

      Eligibility:

        -  Age greater than or equal to 18 years old

        -  Subjects with cytologically or histologically confirmed locally advanced or metastatic
           HPV

      associated malignancies including:

        -  Non-Neuroendocrine Cervical cancers

        -  P16+ Oropharyngeal cancers

        -  Anal cancers

        -  Vulvar, vaginal, penile, squamous cell rectal and neuroendocrine cervical cancers

        -  Other locally advanced or metastatic solid tumors (e.g. lung, esophagus) that are known
           HPV+

             -  Subjects must have measurable disease.

      Design:

      -This is a Phase II trial of M7824 in patients with recurrent or metastatic HPV associated

      malignancies.

      -Patients will be scheduled to receive 1,200 mg of M7824 IV every 2 weeks until off treatment

      criteria are met.

      -There will be six cohorts: (1) Patients with anal cancer whose disease is na"ve to
      checkpoint

      inhibition, (2) Patients with non-neuroendocrine cervical cancer na"ve to checkpoint
      inhibition,

      (3) Patients with P16+ oropharyngeal cancers na"ve to checkpoint inhibition, and (4) Patients
      with other rare HPV associated tumors (e.g. squamous cell rectal, vulvar, vaginal, penile
      cancer, neuroendocrine cervical) na"ve to checkpoint inhibition, (5) Patients with any HPV
      associated cancers whose disease is refractory to checkpoint inhibition. Patients who are
      determined to be HPV negative after enrolling will be taken off of their previously assigned
      cohort and reassigned to cohort 6 and their slot on their previously assigned cohort will be
      replaced.

      -Cohorts 1-5 of the trial will be conducted using a Simon two-stage phase II trial design.
    

Study Phase

Phase 2

Study Type

Interventional


Primary Outcome

Objective response rate (ORR)

Secondary Outcome

 progression-free survival time (PFS)

Condition

Human Papilloma Virus

Intervention

M7824

Study Arms / Comparison Groups

 1/Arm 1
Description:  M7824 at a flat dose of 1,200 mg IV once every 2 weeks

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Drug

Estimated Enrollment

57

Start Date

February 27, 2018

Completion Date

December 31, 2022

Primary Completion Date

February 2, 2021

Eligibility Criteria

        -  INCLUSION CRITIERIA:

          -  Age greater than or equal to 18 years.

          -  Ability of subject to understand and the willingness to sign a written informed
             consent document.

          -  Subjects with cytologically or histologically confirmed locally advanced or metastatic
             HPV associated malignancies including:

               -  Non-Neuroendocrine Cervical cancers

               -  P16+ Oropharyngeal cancers

               -  Anal cancers

               -  Vulvar, vaginal, penile, squamous cell rectal and neuroendocrine cervical cancers

               -  Other locally advanced or metastatic solid tumors (e.g. lung, esophagus) that are
                  known HPV+

          -  Patients must have disease that is not amenable to potentially curative resection

          -  Subjects must have measurable disease

          -  ECOG performance status less than or equal to 2

          -  Adequate hematologic function at screening, as follows:

               -  Absolute neutrophil count (ANC) greater than or equal to 1 x 109/L

               -  Hemoglobin greater than or equal to 9 g/dL

               -  Platelets greater than or equal to 75,000/microliter.

          -  Adequate renal and hepatic function at screening, as follows:

               -  Serum creatinine less than or equal to 1.5 x upper limit of normal (ULN) OR
                  creatinine clearance (CrCl) greater than or equal to 40 mL/min per institutional
                  standard

               -  Bilirubin less than or equal to 1.5 x ULN OR in subjects with Gilbert's syndrome,
                  a total bilirubin less than or equal to 3.0 x ULN

               -  Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) less than or
                  equal to 2.5 x ULN, unless liver metastases are present, then values must be less
                  than or equal to 3 x ULN)

          -  The effects of M7824 on the developing human fetus are unknown; thus, women of
             childbearing potential and men must agree to use adequate contraception (hormonal or
             barrier method of birth control; abstinence) prior to study entry, for the duration of
             study participation and up to 60 days after the last dose of the drug. Should a woman
             become pregnant or suspect she is pregnant while she or her partner is participating
             in this study,she should inform her treating physician immediately.

          -  Patients serologically positive for HIV, Hep B, Hep C are eligible as long as the
             viral loads are undetectable by quantitative PCR. HIV positive patients must have CD4
             count greater than or equal to 300 cells per cubic millimeter at enrollment, be on
             stable antiretroviral therapy and have no reported opportunistic infections within 12
             months prior to enrollment.

        EXCLUSION CRITERIA:

        -Pregnant women are excluded from this study because this drug has not been tested in
        pregnant women and there is potential for teratogenic or abortifacient effects. Because
        there is an unknown but potential risk for adverse events in nursing infants secondary to

        treatment of the mother with M7824, breastfeeding should be discontinued if the mother is
        treated with M7824.

          -  Patients with prior investigational drug, chemotherapy, immunotherapy or any prior
             radiotherapy (except for palliative bone directed therapy) within the past 28 days
             prior to the first drug administration except if the investigator has assessed that
             all residual treatment-related toxicities have resolved or are minimal and feel the
             patient is otherwise suitable for enrollment. Patients may continue adjuvant hormonal
             therapy in the setting of a definitively treated cancer (e.g. breast).

          -  Major surgery within 28 days prior to the first drug administration (minimally
             invasive procedures such as diagnostic biopsies are permitted).

          -  Known intolerance to or life threatening side effects resulting from prior checkpoint
             inhibitor therapy.

          -  Known active brain or central nervous system metastasis (less than 1 month out from
             definitive radiotherapy or surgery), seizures requiring anticonvulsant treatment (<3
             months) or clinically significant cerebrovascular accident (<3 months). In order to be
             eligible patients must have repeat CNS imaging at least two months after definitive
             treatment showing stable CNS disease. Patients with evidence of intratumoral or
             peritumoral hemorrhage on baseline imaging are also excluded unless the hemorrhage is
             grade less than or equal to 1 and has been shown to be stable on two consecutive
             imaging scans.

          -  Active autoimmune disease that might deteriorate when receiving an immunostimulatory
             agent with exception of:

               -  diabetes type I, eczema, vitiligo, alopecia, psoriasis, hypo- or hyperthyroid
                  disease or other mild autoimmune disorders not requiring immunosuppressive
                  treatment;

               -  Subjects requiring hormone replacement with corticosteroids are eligible if the
                  steroids are administered only for the purpose of hormonal replacement and at
                  doses less than or equal to 10 mg of prednisone or equivalent per day;

               -  Administration of steroids for other conditions through a route known to result
                  in a minimal systemic exposure (topical, intranasal, intro-ocular, or inhalation)
                  is acceptable;

               -  Subjects on systemic intravenous or oral corticosteroid therapy with the
                  exception of physiologic doses of corticosteroids (less than or equal to the
                  equivalent of prednisone 10 mg/day) or other immunosuppressives such as
                  azathioprine or cyclosporin A are excluded on the basis of potential immune
                  suppression. For these subjects these excluded treatments must be discontinued at
                  least 1 weeks prior to enrollment for recent short course use (less than or equal
                  to 14 days) or discontinued at least 4 weeks prior to enrollment for long term
                  use (>14 days). In addition, the use of corticosteroids as premedication for
                  contrastenhanced studies is allowed prior to enrollment and on study.

          -  Subjects with a history of serious intercurrent chronic or acute illness, such as
             cardiac or pulmonary disease, hepatic disease, bleeding diathesis or recent (within 3
             months) clinically significant bleeding events, or other illness considered by the
             Investigator as high risk for investigational drug treatment.

          -  History of non-HPV associated second malignancy within 3 years of enrollment except
             localized malignancy which has been adequately treated or malignancy which does not
             require active systemic treatment (e.g. low risk CLL).

          -  Known severe hypersensitivity reactions to monoclonal antibodies (Grade greater than
             or equal to 3 NCI CTCAE v4.03)

          -  Receipt of any organ transplantation requiring ongoing immunosuppression.

          -  Patients with vulvar cancer originating from differentiated vulvar intraepithelial
             neoplasia (d-VIN), as opposed to vulvar intraepithelial neoplasia of usual type, are
             excluded. Vulvar squamous cell carcinoma originating from differentiated VIN (d-VIN)
             is HPV negative; however, rare cases of HPV positive d-VIN can occur. Patients are not
             excluded if their tumor has tested positive for HPV or there is no documentation of
             prior VIN type.

          -  Patients with known HPV negative malignancies based on comprehensive laboratory
             testing (e.g. PCR based assay evaluating for HPV 16, 18, 31, 33, 35, 39, 51, 52, 56,
             58, 59, 66, 68). Patients with HPV associated malignancies and unknown HPV status
             prior to enrollment are eligible.
      

Gender

All

Ages

18 Years - N/A

Accepts Healthy Volunteers

No

Contacts

Julius Y Strauss, M.D., , 

Location Countries

United States

Location Countries

United States

Administrative Informations


NCT ID

NCT03427411

Organization ID

180056

Secondary IDs

18-C-0056

Responsible Party

Sponsor

Study Sponsor

National Cancer Institute (NCI)


Study Sponsor

Julius Y Strauss, M.D., Principal Investigator, National Cancer Institute (NCI)


Verification Date

November 22, 2021