Clinical Trials /

OVSTAR TIL Trial (OVarian Cancer Co-STimulatory Antigen Receptor TIL Trial)

NCT04389229

Description:

An open label, multi-centre Phase 1/2a study of modified and unmodified autologous Tumour Infiltrating Lymphocytes (TIL) in patients with platinum-resistant ovarian cancer. The purpose of this phase I/II study is to evaluate the feasibility and safety of both standard unmodified TIL (UTIL-01) and TIL engineered to express the co-stimulatory receptor CoStAR (CoTIL-01) in platinum resistant ovarian cancer.

Related Conditions:
  • High Grade Ovarian Serous Adenocarcinoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: OVSTAR TIL Trial (OVarian Cancer Co-STimulatory Antigen Receptor TIL Trial)
  • Official Title: Protocol Title: An Open Label, Multi-centre Phase 1/2a Study of Modified and Unmodified Autologous Tumour Infiltrating Lymphocytes (TIL) in Patients With Platinum-resistant Ovarian Cancer

Clinical Trial IDs

  • ORG STUDY ID: IMM-2019T-01-OC
  • SECONDARY ID: 2019-000106-30
  • NCT ID: NCT04389229

Conditions

  • Ovarian Cancer Metastatic

Interventions

DrugSynonymsArms
cyclophosphamideCoTIL-01
fludarabineCoTIL-01
IL-2 (Proleukin)CoTIL-01

Purpose

An open label, multi-centre Phase 1/2a study of modified and unmodified autologous Tumour Infiltrating Lymphocytes (TIL) in patients with platinum-resistant ovarian cancer. The purpose of this phase I/II study is to evaluate the feasibility and safety of both standard unmodified TIL (UTIL-01) and TIL engineered to express the co-stimulatory receptor CoStAR (CoTIL-01) in platinum resistant ovarian cancer.

Detailed Description

      This is a single-arm Phase 1/2a study of unmodified (UTIL-01) and gene modified (CoTIL-01)
      adoptive TIL therapy which will enrol sequentially. A total of 8 patients will be recruited
      to the UTIL-01 cohort to receive autologous standard unmodified TIL (phase 2). Up to 14
      patients will receive autologous gene engineered TIL(CoTIL-1) in a dose escalation design
      (Phase 1/2a). Once patients have met all the pre-screening inclusion criteria, and that
      sponsor has confirmed a successful TIL harvest, a request to manufacture will be sent to the
      Sponsor to initiate TIL production. Manufacturing and quality control assessment is
      anticipated to take approximately 6 weeks. During this time, patients may receive standard of
      care chemotherapy (bridging chemotherapy) as deemed appropriate by the treating oncology
      team. Patients will proceed to the main trial after completion of bridging chemotherapy. Once
      the TIL product is certified for release, and that patient has consented to the main trial
      and has completed main trial screening assessments, study treatment can be scheduled.

      Patients will receive non-myeloablative lymphodepleting pre-conditioning chemotherapy with
      cyclophosphamide 600mg/m2/day and fludarabine 30mg/m2/day on Day -5, -4 and -3. Chemotherapy
      will aim to be delivered as an outpatient, but patients can be admitted if clinically needed.
      Patients will be required to maintain oral hydration of >2 litres per day. If this is felt to
      be difficult to achieve then the patient will be admitted for IV fluids. Patients will be
      admitted for TIL infusion on Day 0. The TIL infusion will be administered at least 36 hours
      after last dose of chemotherapy. The cells will only be thawed once an Investigator has made
      a positive decision to go ahead with infusion and confirmed this in writing. TIL infusion may
      be delayed for up to 7 days for clinical reasons or for issues regarding the cell
      specification. This decision must be made before final preparation for infusion. Following
      TIL infusion, patients will commence subcutaneous interleukin-2 at a fixed dose of 18 million
      units once a day. Patients must remain an inpatient for the duration of IL-2 treatment for a
      minimum of 7 days post TIL infusion. Recruitment to the study will occur over approximately
      24-month period. Recruitment to CoTIL-01 will commence after UTIL-01. Patients will be
      followed up in the study for 24 months post TIL infusion.
    

Trial Arms

NameTypeDescriptionInterventions
UTIL-01ExperimentalSingle dose autologous unmodified tumour infiltrating lymphocytes
  • cyclophosphamide
  • fludarabine
  • IL-2 (Proleukin)
CoTIL-01ExperimentalSingle dose autologous gene modified tumour infiltrating lymphocytes
  • cyclophosphamide
  • fludarabine
  • IL-2 (Proleukin)

Eligibility Criteria

        Inclusion Criteria:

          -  Criteria for Pre-Screening Phase

        Patients are eligible to be included in the pre-screening phase of the study only if all of
        the following criteria apply:

          1. Women with histologically confirmed recurrent metastatic platinum-resistant high-grade
             serous ovarian cancer (HGSOC) (platinum resistant defined as progressing within 6
             months of last platinum-containing combination chemotherapy. Patients must have
             received at least 1 line of prior platinum-containing combination chemotherapy and
             have completed at least 4 cycles of this treatment).

          2. Expected to fulfil all entry criteria for OVSTAR Main Study

          3. Written informed consent to Pre-Screening

          4. Measurable disease by Response Evaluation Criteria in Solid Tumours 1.1

          5. Have disease suitable for fresh TIL harvesting from tumour biopsies (only applicable
             to patients who are not participants of Sponsor's Tumour Collection Programme, PRIME)

          6. Medically suitable for a general anaesthetic and surgical biopsy (only applicable to
             patients who are not participants of Sponsor's Tumour Collection Programme, PRIME)

          7. Women of child bearing potential must be willing to practise a highly effective method
             of birth control once consented to pre-screening

          8. World Health Organisation (WHO) Performance Status of 0 or 1 (Appendix 3)

          9. Age equal to or greater than 18 years

         10. Life expectancy > 6 months

         11. Absence of any psychological, familial, sociological or geographical condition
             potentially hampering compliance with the Pre-Screening or Main Study protocol and
             follow-up schedule; those conditions should be discussed with the patient before
             registration in the trial

         12. Seronegative for HIV antibody, Hep B antigen, Hep C antibody and syphilis

         13. Haematological and biochemical indices

        Exclusion Criteria:

          -  Exclusion for Pre-Screening Phase

        Patients will not be invited to participate in Pre-Screening if any of the following
        criteria apply:

          1. History of a previous malignancy at another site, unless followed for >2 years with no
             sign of recurrent disease (local completely excised cutaneous basal cell, squamous
             cell carcinoma or in situ carcinoma will be allowed).

          2. Patients receiving chemotherapy, targeted therapy, immunotherapy or systemic steroids
             including steroid doses >10mg/day of prednisolone (or equivalent) during the previous
             four weeks prior to TIL harvesting. Patients who require such therapies intermittently
             due to pre-existing disorders are also excluded.

          3. Evidence of any active significant infection.

          4. Patients who have any malignant or likely malignant Central Nervous System (CNS)
             lesion visible on CT.

          5. Evidence of clinically significant immunosuppression such as primary immunodeficiency
             (e.g. severe combined immunodeficiency disease).

          6. Clinically significant cardiac disease. Examples would include unstable coronary
             artery disease, myocardial infarction within 6 months or class III or IV American
             Heart Association criteria for heart disease.

          7. Patients who are at high medical risk because of non-malignant systemic disease
             including those with uncontrolled cardiac or respiratory disease, or other serious
             medical or psychiatric disorders which, in the lead clinician's opinion, would not
             make the patient a good candidate for adoptive TIL therapy.

          8. Severe and active autoimmune disease.

          9. On concomitant treatment with other experimental drugs within 4 weeks of TIL
             harvesting.

         10. Patients not considered likely to comply with required follow up.

         11. Patients with severe allergies, history of anaphylaxis or known allergies to the
             administered drugs.

         12. Patients who have received any prior adoptive cell therapy or organ transplant
             (including stem cells).

         13. Patients who are pregnant or breast feeding should be excluded from pre-screening

         14. Patients with any contraindications to any of the components of the study Non
             Investigational Medicinal Products (cyclophosphamide, fludarabine, Interleukin-2) will
             be excluded

         15. Patents who have received live vaccines within 4 weeks prior to TIL therapy will be
             excluded

        Inclusion for Main Study

        -Patients are eligible to be included in the Main Study only if all of the following
        criteria, and the inclusion criteria listed in Section 1.3.1, apply:

          1. Women with metastatic platinum resistant high-grade serous ovarian cancer (HGSOC) who
             have recurrent disease (platinum resistant defined as progressing within 6 months of
             last platinum-containing combination chemotherapy. patients must have received at
             least 1 line of prior platinum-containing combination chemotherapy and have completed
             at least 4 cycles of this treatment).

          2. Informed consent to Main Study

          3. Confirmation from Sponsor of successful TIL growth

          4. Measurable disease (by Response Evaluation Criteria in Solid Tumors 1.1) on CT within
             4 weeks of main study entry

          5. Left ventricular ejection fraction >50% on Echocardiogram scan

          6. Patients must be willing to practice a highly effective method of birth control during
             treatment and for four months after receiving the preparative regime if appropriate.

          7. World Health Organisation (WHO) Performance Status of 0 or 1 (Appendix 3)

          8. Age equal to or greater than 18 years

          9. Life expectancy > 6 months

         10. Absence of any psychological, familial, sociological or geographical condition
             potentially hampering compliance with the Pre-Screening or Main Study protocol and
             follow-up schedule; those conditions should be discussed with the patient before
             registration in the trial

         11. Seronegative for HIV antibody, Hep B antigen, Hep C antibody and syphilis

         12. Haematological and biochemical indices

        Exclusion for Main Study

          1. Patients receiving day 1 of their last cycle of chemotherapy or targeted therapy less
             than four weeks prior to pre-conditioning chemotherapy.

          2. Patients receiving systemic immunosuppressive therapy including steroids at doses
             higher than 10mg/day of prednisolone (or equivalent) within four weeks of commencing
             pre-conditioning chemotherapy (unless this is required briefly as anti-emetic
             prophylaxis for the treatments detailed in above point 1). Patients who require such
             therapies intermittently due to pre-existing disorders are also excluded.

          3. Patients who have any malignant or likely malignant Central Nervous System (CNS)
             lesion visible on CT.

          4. Evidence of any active significant infection.

          5. Evidence of clinically significant immunosuppression such as primary immunodeficiency
             (e.g. severe combined immunodeficiency disease).

          6. Clinically significant cardiac disease. Examples would include unstable coronary
             artery disease, myocardial infarction within 6 months or class III or IV American
             Heart Association criteria for heart disease.

          7. Patients who are at high medical risk because of non-malignant systemic disease
             including those with uncontrolled cardiac or respiratory disease, or other serious
             medical or psychiatric disorders which, in the lead clinician's opinion, would not
             make the patient a good candidate for adoptive TIL therapy.

          8. Severe and active autoimmune disease.

          9. Receiving concomitant treatment with any other experimental drugs within 4 weeks of
             pre-conditioning chemotherapy. Patients receiving experimental immunotherapies will be
             discussed with the sponsor.

         10. Patients not considered likely to comply with required follow up.

         11. Patients with severe allergies, history of anaphylaxis or known allergies to the
             administered drugs.

         12. Patients who are pregnant or breast feeding should be excluded from entering the study

         13. Patients who have received any prior adoptive cell therapy or organ transplant
             (including stem cells).

         14. Caution should be exercised for patients requiring regular drainage of ascites or
             pleural effusions. When there is sufficient fluid to be safely drained, drainage must
             be performed prior to trial enrolment and pre-conditioning chemotherapy in those
             patients.

         15. Patients with any contraindications to any of the components of the study Non
             Investigational Medicinal Products (cyclophosphamide, fludarabine, Interleukin-2) will
             be excluded

         16. Patents who have received live vaccines within 4 weeks prior to TIL therapy will be
             excluded.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure:Disease objective response according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria
Time Frame:6 weeks post treatment
Safety Issue:
Description:Subjects will have CT scan at 6 weeks post treatment to compare with baseline CT scans in order to assess disease response to therapy

Secondary Outcome Measures

Measure:Percentage change in CA125 according to the Gynaecologic Cancer InterGroup CA125 response definition
Time Frame:up to 24 months post TIL therapy
Safety Issue:
Description:Serum level of CA125 will be measured in patients on day of discharge, 4weeks, 6weeks,12weeks and 3 monthly post TIL treatment
Measure:Feasibility assessed by successful completion of planned treatment.
Time Frame:5 days post TIL therapy
Safety Issue:
Description:Subjects will receive lymphodepletion followed by a single TIL treatment and supportive IL-2
Measure:Progression free survival
Time Frame:up to 24 months post TIL therapy
Safety Issue:
Description:This will be measured by time from treatment initiation (from first day of pre-conditioning chemotherapy to radiological disease progression, relapse or death due to any cause
Measure:Duration of overall response and stable disease
Time Frame:up to 24 months post TIL therapy
Safety Issue:
Description:This is measured by time from response until radiological progression
Measure:Tolerability and safety assessed according to NCI CTCAE v5.0 grading
Time Frame:up to 24 months post TIL therapy
Safety Issue:
Description:Any adverse events related to study treatment will be recorded and assessed
Measure:Objective response by RECIST v1.1
Time Frame:up to 24months post TIL therapy
Safety Issue:
Description:Subjects who have received CoTIL-01 will have CT scan at 6 weeks, 12 weeks, then very 12 weeks post treatment to compare with baseline and previous post treatment CT scans in order to assess disease response to therapy

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Immetacyte Ltd

Last Updated

May 11, 2020