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

NCT04389229 | Withdrawn Phase 1 DMC

• 2 other identifiers: IMM-2019T-01-OC2019-000106-30
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Ovarian Cancer Metastatic

Outcome Measures

Primary Outcomes (5)

• Disease objective response according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria

  Subjects will have CT scan at 6 weeks post treatment to compare with baseline CT scans in order to assess disease response to therapy

  6 weeks post treatment

• Disease objective response according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria

  Subjects will have CT scan at 12 weeks post treatment to compare with baseline and previous post treatment CT scans in order to assess disease response to therapy

  12weeks post treatment

• Disease objective response according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria

  Subjects will have CT scan every 12 weeks after week 12 post treatment to compare with baseline and previous post treatment CT scans in order to assess disease response to therapy

  up to 24 months post treatment

• Feasibility of treatment assessed by successful completion of planned treatment

  Subjects will receive lymphodepletion followed by a single TIL treatment and supportive IL-2

  5 days post TIL therapy

• Tolerability and safety assessed according to NCI CTCAE v5.0 grading.

  Any adverse events related to study treatment will be recorded and assessed

  up to 24 months post TIL therapy

Secondary Outcomes (6)

• Percentage change in CA125 according to the Gynaecologic Cancer InterGroup CA125 response definition

  up to 24 months post TIL therapy

• Feasibility assessed by successful completion of planned treatment.

  5 days post TIL therapy

• Progression free survival

  up to 24 months post TIL therapy

• Duration of overall response and stable disease

  up to 24 months post TIL therapy

• Tolerability and safety assessed according to NCI CTCAE v5.0 grading

  up to 24 months post TIL therapy

Study Arms (2)

UTIL-01

EXPERIMENTAL

Single dose autologous unmodified tumour infiltrating lymphocytes

Drug: cyclophosphamide; Drug: fludarabine; Drug: IL-2 (Proleukin); Genetic: Unmodified Tumour Infiltrating Lymphocytes (UTIL-01)

CoTIL-01

EXPERIMENTAL

Single dose autologous gene modified tumour infiltrating lymphocytes

Drug: cyclophosphamide; Drug: fludarabine; Drug: IL-2 (Proleukin); Genetic: Gene modified Tumour Infiltrating Lymphocytes (CoTIL-01)

Interventions

cyclophosphamide DRUG

600mg/m2/day for 3 days ( on day -5, -4, -3)

CoTIL-01; UTIL-01

fludarabine DRUG

30mg/m2/day for 3 days ( on day -5, -4, -3)

CoTIL-01; UTIL-01

IL-2 (Proleukin) DRUG

Subcutaneous injections at a fixed dose of 18 million units once a day following TIL infusion

CoTIL-01; UTIL-01

Unmodified Tumour Infiltrating Lymphocytes (UTIL-01) GENETIC

Single dose at 5 x 10\^9 - 5 x 10\^10

Also known as: TIL

UTIL-01

Gene modified Tumour Infiltrating Lymphocytes (CoTIL-01) GENETIC

Single dose at 2 x10\^9 (+/- 20%) (engineered TIL)

Also known as: engineeredTIL

CoTIL-01

Eligibility Criteria

• Age: 18 Years+
• Gender Eligibility Details: Sex of participants based on biological sex not self-representation as disease area being studied is Ovarian Cancer
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• 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).
• Expected to fulfil all entry criteria for OVSTAR Main Study
• Written informed consent to Pre-Screening
• Measurable disease by Response Evaluation Criteria in Solid Tumours 1.1
• 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)
• Medically suitable for a general anaesthetic and surgical biopsy (only applicable to patients who are not participants of Sponsor's Tumour Collection Programme, PRIME)
• Women of child bearing potential must be willing to practise a highly effective method of birth control once consented to pre-screening
• World Health Organisation (WHO) Performance Status of 0 or 1 (Appendix 3)
• Age equal to or greater than 18 years
• Life expectancy \> 6 months
• 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
• Seronegative for HIV antibody, Hep B antigen, Hep C antibody and syphilis
• Haematological and biochemical indices

You may not qualify if:

• Patients will not be invited to participate in Pre-Screening if any of the following criteria apply:
• 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).
• 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.
• Evidence of any active significant infection.
• Patients who have any malignant or likely malignant Central Nervous System (CNS) lesion visible on CT.
• Evidence of clinically significant immunosuppression such as primary immunodeficiency (e.g. severe combined immunodeficiency disease).
• 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.
• 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.
• Severe and active autoimmune disease.
• On concomitant treatment with other experimental drugs within 4 weeks of TIL harvesting.
• Patients not considered likely to comply with required follow up.
• Patients with severe allergies, history of anaphylaxis or known allergies to the administered drugs.
• Patients who have received any prior adoptive cell therapy or organ transplant (including stem cells).
• Patients who are pregnant or breast feeding should be excluded from pre-screening
• Patients with any contraindications to any of the components of the study Non Investigational Medicinal Products (cyclophosphamide, fludarabine, Interleukin-2) will be excluded

Sponsors & Collaborators

• Immetacyte Ltd: lead

Study Sites (2)

Queens Elizabeth Hospital

Birmingham, United Kingdom

Location

The Christies Hospital

Manchester, United Kingdom

Location

MeSH Terms

Interventions

Cyclophosphamide; fludarabine; Interleukin-2; aldesleukin

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Interleukins; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Lymphokines; Proteins; Biological Factors

Study Officials

• Fiona Thistlethwaite, PhD, MRCP

  The Christie Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: This study has two cohorts which will open sequentially. This is not a randomized controlled trial.

Study Record Dates

• First Submitted: January 22, 2020
• First Posted: May 15, 2020
• Study Start: July 1, 2020
• Primary Completion: March 31, 2023
• Study Completion: July 31, 2025
• Last Updated: December 16, 2020

Record last verified: 2020-12

Data Sharing

• IPD Sharing: Will not share

Locations

GB (2)