A Safety Study of NUC-7738 in Patients With Advanced Solid Tumours or Lymphoma

• Status: Recruiting
• Trial end date: 2022-07-01
• Target enrollment: 0
• Participant gender: All

Summary

This is a two-part, Phase I, dose-escalation study of NUC-7738 administered by intravenous infusion across two administration schedules.

Part 1 is a dose-escalation study in patients with advanced solid tumours to assess the safety and tolerability of NUC-7738, in addition to establishing the recommended phase II dose (RP2D) and dose administration schedule of NUC-7738 for further exploration in Part 2 of the study.

Part 2 will further evaluate the selected RP2D and designated dosing schedule in an expansion cohort of approximately 40 additional patients with advanced solid tumours and approximately 12 patients with lymphoma.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: NuCana plc

Criteria

Inclusion Criteria:

1. Provision of signed written informed consent

2. Histologically confirmed diagnosis of an advanced solid tumour (Part 1 and 2) or lymphoma (Part 2 only), which is not amenable to standard chemotherapy, is refractory to standard chemotherapy, or for which no standard chemotherapy exists

3. Age ≥18 years (no upper age limit)

4. Eastern Cooperative Oncology Group performance status of 0 or 1

5. Life expectancy of ≥12 weeks

6. Part 1 and Part 2: enrolment of patients with advanced solid tumours. Patients must have measurable disease as per RECIST v1.1 criteria and/or evaluable disease (evaluable: cytologically or radiologically detectable disease such as ascites, peritoneal deposits, or lesions, which do not fulfil RECIST v1.1 criteria for measurable disease) for solid tumours.

7. Part 2: enrolment of patients with lymphoma. Patients must have bi-dimensionally measurable disease as per Cheson et al, 2007 criteria for lymphoma.

8. Adequate bone marrow, liver, and renal function

9. Ability to comply with protocol requirements

10. Patients of child-bearing potential must agree to practice true abstinence or to use two highly effective forms of contraception, one of which must be a barrier method of contraception, from the time of screening until 30 days after the last dose of study medication.

11. Willing to undergo biopsy of suitably accessible lesions. Patients who do not have easily accessible tumour for biopsy should not be put at undue risk for sample collection and these patients remain eligible for the study.

Exclusion Criteria:

1. History of allergic reaction fo any of the components of NUC-7738

2. Symptomatic central nervous system or leptomeningeal metastases

3. Chemotherapy, radiotherapy (other than a short cycle of palliative radiotherapy for bone pain), immunotherapy, or exposure to another investigational agent within 28 days (for biological agents decision on washout period will be made on a case by base basis) of first administration of the IMP:

1. For nitrosoureas and mitomycin C within 6 weeks of first administration of NUC-7738

2. For hormone therapy within 14 days of first administration of NUC-7738

3. Corticosteroid treatment is allowed during the screening period but should be weaned to a dose of 10 mg prednisolone (or steroids equivalent) by Cycle 1 Day 1.

4. Prior toxicities from anti-cancer agents or radiotherapy, which have not regressed to Grade ≤1 severity (NCI-CTCAE v5.0), excluding neuropathy and alopecia

5. Presence of any uncontrolled concomitant illness, serious illness, medical conditions, or other medical history, including laboratory results, which, in the Investigator's opinion, would be likely to interfere with their participation in the study, or with the interpretation of results, including the following:

1. Congestive heart failure (New York Heart Association Class III or Class IV)

2. Myocardial infarction within 6 months of the first dose of study medication

3. Unstable or poorly controlled angina pectoris

4. Complete left bundle branch, bifasicular block or other clinically significant abnormal electrocardiogram finding

5. A history of or current risk factor for Torsades de Point (e.g., heart failure, hypokalaemia, or a family history of long QT syndrome)

6. A history of, or current diagnosis of, interstitial pneumonitis or pulmonary fibrosis

6. Known human immunodeficiency virus positive or known active hepatitis B or C. Presence of an active bacterial or viral infection including Herpes zoster or chicken pox

7. Any condition (e.g., known or suspected poor compliance, psychological instability, geographical location etc.) that, in the judgment of the Investigator, may affect the patient's ability to sign the informed consent and undergo study procedures

8. Currently pregnant, lactating or breastfeeding

9. QTc interval >450 milliseconds for males and >470 milliseconds for females

10. Concomitant use of drugs known to prolong QT/QTc interval

11. Have received a live vaccination within four weeks of first planned dose of study medication.