NCT02941523

Safety, PK and Efficacy of NOX66 as a Monotherapy and Combined With Carboplatin in Refractory Solid Tumours

Completed Phase 1, PHASE2 Results posted Last updated 2 June 2021

What this trial tests

Phase 1, PHASE2 trial testing NOX66 in Cancer in 19 participants. Completed in 10 January 2019.

Timeline

3 March 2017

Primary endpoint
31 December 2018

10 January 2019

Quick facts

Lead sponsor	Noxopharm Limited
Phase	Phase 1, PHASE2
Status	Completed
Study type	INTERVENTIONAL
Allocation	non randomized
Design	single group
Masking	single
Primary purpose	treatment
Enrollment	19
Start date	3 March 2017
Primary completion	31 December 2018
Estimated completion	10 January 2019
Sites	4 locations across Georgia

Drugs / interventions tested

• NOX66 — full drug profile →
• Carboplatin (Carboplatin) — full drug profile →

Conditions studied

• Cancer — all drugs for Cancer →

Sponsor

Noxopharm Limited — full company profile →

Who can join

18 and older, any sex, with Cancer. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Number of Participants Who Experience Dose Limiting Toxicity (DLT) During NOX66 Monotherapy and During NOX66 Combination With Carboplatin Primary · Up to 1 month for NOX66 monotherapy from enrollment and up to 7 months from start of NOX66 combination therapy

Dose limiting toxicity during monotherapy and combination therapy defined as any Grade 3 or more toxicity (by National Cancer Institute Common Terminology Criteria for Adverse Events \[NCI CTCAE version 4.03\]) (related to therapy) excluding Grade 3 or more neutropenia lasting greater than 5 days or thrombocytopenia associate with bleeding or Grade 4 thrombocytopenia.

Group	Value	95% CI
NOX66 400 mg Monotherapy	0
NOX66 400 mg Combination Therapy	0
NOX66 800 mg Monotherapy	0
NOX66 800 mg Combination Therapy	0

Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Treatment Emergent Adverse Events (SAEs) Related to NOX66. Primary · From enrollment through 30 days after the last cycle of therapy (8 months)

An AE was defined as any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug. A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. Treatment-emergent are events between first dose of study drug that were absent before

Group	Value	95% CI
NOX66 400 mg Monotherapy	0
NOX66 400 mg Combination Therapy	0
NOX66 800 mg Monotherapy	1
NOX66 800 mg Combination Therapy	0

Objective Response Rate (ORR) at Cycle 3 and at Cycle 6 of Combination Therapy Secondary · Radiological evaluation at baseline and at 3 months and at 6 months

Objective response rate defined as the percentage of participants achieving a complete response (CR) and or partial response (PR) after treatment with NOX66 and carboplatin therapy as assessed by Response Evaluation Criteria in solid tumors (RECIST) v1.1. CR defined as disappearance of all target and non-target lesions and reduction of any pathological lymph nodes (whether target or non-target) to \<10 mm in short axis; PR was defined by a 30% or more decrease in sum of longest diameter (SLD) of target lesions in reference to baseline. PR or better overall response assumes at a minimum incomp

Complete Response

Group	Value	95% CI
NOX66 400 mg + Carboplatin (AUC4) to Cycle 3	0
NOX66 400 mg + Carboplatin (AUC6) to Cycle 6	0
NOX66 800 mg + Carboplatin (AUC4) to Cycle 3	0
NOX66 800 mg + Carboplatin (AUC6) to Cycle 6	0

Partial Response

Group	Value	95% CI
NOX66 400 mg + Carboplatin (AUC4) to Cycle 3	0
NOX66 400 mg + Carboplatin (AUC6) to Cycle 6	0
NOX66 800 mg + Carboplatin (AUC4) to Cycle 3	0
NOX66 800 mg + Carboplatin (AUC6) to Cycle 6	1

Overall Clinical Response Rate at Cycle 3 and at Cycle 6 of Combination Therapy Secondary · Radiological evaluation at baseline and at 3 months and at 6 months

Overall Clinical response rate defined as the percentage of participants who achieved complete response (CR) or partial response (PR) or stable disease (SD) as assessed by Response Evaluation Criteria In Solid Tumors (RECIST) criteria v1.1 after combination of NOX66 and carboplatin therapy. CR defined as disappearance of all target and non-target lesions and reduction of any pathological lymph nodes (whether target or non-target) to \<10 mm in short axis; PR was defined by a 30% or more decrease in sum of longest diameter (SLD) of target lesions in reference to baseline. Stable disease (SD)=N

Group	Value	95% CI
NOX66 400 mg + Carboplatin (AUC4) to Cycle 3	4
NOX66 400 mg + Carboplatin (AUC6) to Cycle 6	1
NOX66 800 mg + Carboplatin (AUC4) to Cycle 3	7
NOX66 800 mg + Carboplatin (AUC6) to Cycle 6	5

Adverse events — posted to ClinicalTrials.gov

Time frame: 7 months. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Monotherapy Phase, NOX66 400 mg

Serious: 0/8 (0%)

Deaths: 0/8

Monotherapy Phase, NOX66 800 mg

Serious: 0/7 (0%)

Deaths: 0/7

Combination Phase, NOX66 400 mg

Serious: 1/8 (13%)

Deaths: 1/8

Combination Phase, NOX66 800 mg

Serious: 3/10 (30%)

Deaths: 2/10

Serious adverse events (4 terms)

Reaction	System	Monotherapy Phase, NOX66 4…	Monotherapy Phase, NOX66 8…	Combination Phase, NOX66 4…	Combination Phase, NOX66 8…
sudden death	General disorders	—	—	—	—
Infusion reaction	Injury, poisoning and procedural complications	—	—	—	—
Coma	Nervous system disorders	—	—	—	—
haemorrhage	Gastrointestinal disorders	—	—	—	—

Other adverse events (22 terms — click to expand)

Reaction	System	Monotherapy Phase, NOX66 4…	Monotherapy Phase, NOX66 8…	Combination Phase, NOX66 4…	Combination Phase, NOX66 8…
Anaemia	Blood and lymphatic system disorders	—	—	—	—
Neutropenia	Blood and lymphatic system disorders	—	—	—	—
Hypocalcaemia	Metabolism and nutrition disorders	—	—	—	—
Iron deficiency anaemia	Blood and lymphatic system disorders	—	—	—	—
Pericarditis	Cardiac disorders	—	—	—	—
Abdominal pain, upper	Gastrointestinal disorders	—	—	—	—
Diarrhoea	Gastrointestinal disorders	—	—	—	—
Flatulence	Gastrointestinal disorders	—	—	—	—
Nausea	Gastrointestinal disorders	—	—	—	—
Asthenia	General disorders	—	—	—	—
Platelet count decreased	Investigations	—	—	—	—
Weight decreased	Investigations	—	—	—	—
White blood cell count increased	Investigations	—	—	—	—
Hypoalbuminaemia	Metabolism and nutrition disorders	—	—	—	—
Back pain	Musculoskeletal and connective tissue disorders	—	—	—	—
Altered state of consciousness	Nervous system disorders	—	—	—	—
Dizziness	Nervous system disorders	—	—	—	—
Neuropathy, peripheral	Nervous system disorders	—	—	—	—
Hydrothorax	Respiratory, thoracic and mediastinal disorders	—	—	—	—
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	—	—	—	—
Pulmonary fibrosis	Respiratory, thoracic and mediastinal disorders	—	—	—	—
Embolism, arterial	Vascular disorders	—	—	—	—

Most-reported serious reactions: sudden death, Infusion reaction, Coma, haemorrhage.

Data from ClinicalTrials.gov NCT02941523 adverse events section.

Sponsor's own description

The study evaluates the safety and activity of NOX66 in patients with refractory solid tumors that are non responsive to standard therapies.

This is a two part with a potential third part, open-label, multicenter, dose escalation study of NOX66 as monotherapy and in combination with carboplatin.

Publications & conference data

2 peer-reviewed publications reference this trial (live from Europe PMC):

1. The STING in Non-Alcoholic Fatty Liver Diseases: Potential Therapeutic Targets in Inflammation-Carcinogenesis Pathway.
   Lv J, Xing C, Chen Y, Bian H, et al · · 2022 · cited 9× · PMID 36297353 · DOI 10.3390/ph15101241
2. The role of autophagic kinases in regulation of axonal function.
   Berth SH, Rich DJ, Lloyd TE. · · 2022 · cited 3× · PMID 36226074 · DOI 10.3389/fncel.2022.996593