Nivolumab and Pembrolizumab Dose Optimisation in Solid Tumours With CURATE.AI Platform and Sequential ctDNA Measurements

NCT05175235 | Unknown Phase 1

• 1 other identifier: 2020/00334-Immunotherapy
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

CURATE.AI - a small data, AI-derived technology platform - allows personalised guidance of an individual's dose modulations based only on that individual's data. Additionally, CURATE.AI is mechanism-independent, and dynamically adapts to changes experienced by the subject, providing dynamic dose optimisation throughout the duration of the subject's treatment. This study aims to demonstrate the feasibility of applying CURATE.AI in standard of care settings for treatment of solid tumours with Nivolumab. An additional objective is to explore sequential ctDNA measurements as a response marker collected at a higher frequency of probing, with modulated doses.

Conditions

Solid Tumor

Keywords

personalized oncology; personalized dose selection; immunotherapy; dose optimisation; Cancer; Artificial Intelligence; CURATE.AI; Nivolumab; Sequential ctDNA; Chemotherapy

Outcome Measures

Primary Outcomes (1)

• Percentage of participants in whom we successfully apply CURATE.AI profile.

  CURATE.AI applicability: Percentage of participants in whom we successfully apply CURATE.AI profile. Based on percentages, outcomes will be classified as Green (\>70%) / Yellow (10-70%) / Red (\<10%). A decision on whether we "successfully apply" the CURATE.AI profile requires expert judgement and cannot be made based on a purely numerical process. The expert panel will consider the following factors with careful regard for the individual circumstances of each participant: Error/variance (biological/analytical) is sufficiently small to allow accurate predictions Profile can be generated sufficiently early for the participant to potentially benefit; Dose-dependent relationship is observed; Profile is actionable (i.e. fulfils the clinical investigator's pre-specified safety requirements); Systemic changes in the participant which require profile recalibration are rare or readily assimilated into the CURATE.AI algorithm

  up to 12 months

Secondary Outcomes (5)

• Patient adherence

  Up to 12 months

• Timely delivery of CURATE.AI recommendations to the clinician

  Up to 12 months

• CURATE.AI relevance

  Up to 12 months

• Physician adherence

  Up to 12 months

• Clinically significant dose changes

  Up to 12 months

Other Outcomes (5)

• Percentage of trial participants with clinical progressive disease

  Up to 12 months

• Temporal variation in response marker (ctDNA) level from baseline to trial conclusion.

  Up to 12 months

• Maximal reduction in response marker (ctDNA) level measured as part of baseline investigations

  Up to 12 months

Study Arms (1)

CURATE.AI

EXPERIMENTAL

Participants will undergo two treatment periods: selection period and CURATE.AI modulation period. During the selection period, baseline ctDNA measurements and CT scans will be performed. Subsequently, participants will receive Standard of Care (SOC) doses of nivolumab/pembrolizumab and have their ctDNA measured at the end of the third cycle together with other SOC monitoring. After the first ctDNA measurement and CT scan, selected patients who responded to treatment through both ctDNA and CT scan may continue into the CURATE.AI modulation period. Non-responders will receive SOC doses of nivolumab/pembrolizumab for 2 cycles before having their ctDNA measured and CT scan at the end of the 2 cycles. Subsequent responders through both ctDNA and CT scans may then continue into the CURATE.AI modulation period. Only the dose of nivolumab/pembrolizumab will be modulated with CURATE.AI, based on measurements of the response marker (ctDNA).

Device: CURATE.AI; Drug: Nivolumab, Pembrolizumab

Interventions

CURATE.AI DEVICE

Efficacy and toxicity measurements at the end of each two-/three- week dosing cycle, together with an information on given drugs and their doses, and other patient data, will be used by CURATE.AI to recommend the dose of nivolumab/pembrolizumab for the next cycle. The clinical investigators will decide whether or not to administer or prescribe the dose recommendation from CURATE.AI.

CURATE.AI

Nivolumab, Pembrolizumab DRUG

Treatment with the selected regimen will take up to a maximum duration of 12 months, in two-/three- week cycles. CURATE.AI dose recommendations will be generated before each chemotherapy cycle; fixed throughout the cycle; Maximum total cumulative dose per cycle of nNivolumab/pembrolizumab in the predetermined safety range is set at 100% of standard starting dose (i.e. , 240 mg/m2 once every 2 weeks for single agent Nivolumab and 200 mg/m2 once every 3 weeks for single agent Pembrolizumab). Minimum total cumulative dose per cycle of nivolumab/pembrolizumab in the predetermined safety range is set at 30% of the standard starting dose (i.e. 8072 mg/m2 once every 2 weeks for single agent Nivolumab and 60 mg/m2 once every 3 weeks for single agent Pembrolizumab). Subject-specific dosing range may alter those numbers to suit the specific circumstances of the subject, thus giving the subject specific safe dosing range.

CURATE.AI

Eligibility Criteria

• Age: 21 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Males and females ≥ 21 years of age
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 2.
• Patients must meet the following clinical laboratory criteria within 21 days of starting treatment:
• Absolute neutrophil count (ANC) ≥ 1,000/mm3 and platelet ≥ 50,000/mm3
• Total bilirubin ≤ 1.5 x the upper limit of the normal range (ULN). Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3 x ULN of ≤ 5 ULN if involvement of the liver.
• Calculated creatinine clearance ≥ 30 mL/min or creatinine \< 1.5 x ULN.
• Main tumour types: Non-small cell lung cancer (NSCLC), gastric cancer (GC), hepatocellular carcinoma (HCC) and nasopharyngeal carcinoma (NPC) or other metastatic solid tumours not for curative intent therapy;
• Treatment with combinational immunotherapy or single-agent nivolumab/pembrolizumab. If patients have already started treatment on this regimen, they may still be eligible to enrol, provided they fulfil all other criteria and approval is sought by PI and Sponsor.
• Eligible for treatment combinational immunotherapy or single-agent nivolumab /pembrolizumab based on co-investigator's assessment of fitness for immunotherapy (e.g. not on high dose corticosteroid therapy or uncontrolled auto-immune disorder)

You may not qualify if:

• Patients who are lactating or pregnant.
• Patients with clinically significant hypersensitivity to one or more of the selected regimen's constituent drug(s)
• Contraindication to any of the required concomitant drugs or supportive treatments.
• Any clinically significant medical disease or psychiatric condition that, in the co-investigator's opinion, may interfere with protocol adherence or a subject's ability to give informed consent.
• Major surgery within 28 days prior to start of the treatment,
• Active congestive heart failure (New York Heart Association \[NYHA\] Class III or IV), symptomatic ischaemia, or conduction abnormalities uncontrolled by conventional intervention. Myocardial infarction within 4 months prior to informed consent obtained.

Sponsors & Collaborators

• National University Hospital, Singapore: lead
• The N.1 Institute for Health (N.1): collaborator
• Natera, Inc.: collaborator

Study Sites (1)

National University Hospital

Singapore, 119074, Singapore

RECRUITING

Related Publications (5)

• Lin JC, Wang WY, Chen KY, Wei YH, Liang WM, Jan JS, Jiang RS. Quantification of plasma Epstein-Barr virus DNA in patients with advanced nasopharyngeal carcinoma. N Engl J Med. 2004 Jun 10;350(24):2461-70. doi: 10.1056/NEJMoa032260.

  PMID: 15190138 BACKGROUND

• Kazandjian D, Suzman DL, Blumenthal G, Mushti S, He K, Libeg M, Keegan P, Pazdur R. FDA Approval Summary: Nivolumab for the Treatment of Metastatic Non-Small Cell Lung Cancer With Progression On or After Platinum-Based Chemotherapy. Oncologist. 2016 May;21(5):634-42. doi: 10.1634/theoncologist.2015-0507. Epub 2016 Mar 16.

  PMID: 26984449 RESULT

• Evan TH, Jenny Z, Eun-Jeong K, Grace H, Shailender B, Sunil AR. Economic analysis of alternative pembrolizumab and nivolumab dosing strategies at an academic cancer centre. JCO 2019; 37(15): 6504-6504. doi: 10.1200/JCO.2019.37.15_suppl.6504

  RESULT

• Yoo SH, Keam B, Kim M, Kim SH, Kim YJ, Kim TM, Kim DW, Lee JS, Heo DS. Low-dose nivolumab can be effective in non-small cell lung cancer: alternative option for financial toxicity. ESMO Open. 2018 Jul 25;3(5):e000332. doi: 10.1136/esmoopen-2018-000332. eCollection 2018.

  PMID: 30094065 RESULT

• Low JL, Huang Y, Sooi K, Ang Y, Chan ZY, Spencer K, Jeyasekharan AD, Sundar R, Goh BC, Soo R, Yong WP. Low-dose pembrolizumab in the treatment of advanced non-small cell lung cancer. Int J Cancer. 2021 Jul 1;149(1):169-176. doi: 10.1002/ijc.33534. Epub 2021 Mar 6.

  PMID: 33634869 RESULT

MeSH Terms

Conditions

Neoplasms

Interventions

Nivolumab; pembrolizumab

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Raghav Sundar

  NUH

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Raghav Sundar

CONTACT

+65 6779 5555; raghav_sundar@nuhs.edu.sg

Michelle Au

CONTACT

Michelle_YX_AU@nuhs.edu.sg

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This is a multi-centre, one-arm, prospective pilot study of participants diagnosed with solid tumours. The participants will be enrolled for the duration of their treatment with Nivolumab. At 12-month mark, the decision on the patient engagement with the study will be made by the principal investigator in consultation with the study sponsors and treating physician.

Study Record Dates

• First Submitted: December 14, 2021
• First Posted: January 3, 2022
• Study Start: August 19, 2021
• Primary Completion: May 31, 2023
• Study Completion: August 1, 2023
• Last Updated: March 3, 2023

Record last verified: 2023-01

Data Sharing

• IPD Sharing: Will not share

Locations

SG (1)