A Study to Evaluate the Combination of Nivolumab With ADG106 in Metastatic NSCLC

NCT05236608 | Unknown Phase 1

• 3 other identifiers: STCC-02CA209-63CADG106-T6001
• Study Type: interventional
• Target: 53
• Locations: 1 country
• Sites: 2

Brief Summary

This is an open label, non-randomised phase 1b/2 study including patients with non-small cell lung cancer who have progressed after treatment with immune checkpoint inhibitors (anti PD1/PDL1 with or without CTLA4 inhibitors) and platinum-based chemotherapy. The study medications include nivolumab, an anti-PD1 inhibitor and ADG106, an agonist antibody of 4-1-BB. The investigators hypothesize that the combination of nivolumab and ADG106 would be tolerable, and demonstrate significant clinical anti-tumour activity in patients with NSCLC that has failed antiPD1/antiPDL1 immunotherapy and standard platinum-based chemotherapy. The investigators propose to conduct a phase 1b/2 study to investigate this strategy.

Conditions

Metastatic Non Small Cell Lung Cancer

Outcome Measures

Primary Outcomes (2)

• Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE v5.0

  Adverse events profile, safety profile of the combination of ADG106 and nivolumab according to the NCI Common Terminology Criteria for Adverse Events Version 5.0 (CTCAE v5.0).

  45 months

• Objective response rate

  Objective response rate (CR + PR) using RECIST 1.1 of the combination of ADG106 and nivolumab in patients with metastatic NSCLC that have progressed after antiPD1/PDL1 treatment and platinum-based chemotherapy (phase 2).

  24 months

Secondary Outcomes (3)

• Progression free survival at 6 months

  6 months

• Area Under the Curve [AUC]

  Baseline until Cycle 2 Day 1, each cycle is 21 days

• Maximum Plasma Concentration [Cmax]

  Baseline until Cycle 2 Day 1, each cycle is 21 days

Study Arms (1)

Nivolumab and ADG106

EXPERIMENTAL

Eligible patients will receive nivolumab and ADG106 by IV infusion according to the study phases below. Phase 1b: 3 evaluable patients will be treated at the starting dose, and assessed for tolerability over the first cycle. Treatment related dose-limiting toxicities (DLT) will determine the next dose level to be studied. Dose escalation will follow the 3 + 3 study dose titration design. Phase 2: The dose of ADG106 given together with nivolumab will be the recommended dose in combination with nivolumab determined in phase 1b.

Drug: Nivolumab; Drug: ADG106

Interventions

Nivolumab DRUG

Administered together with ADG106 via intravenous infusion.

Also known as: Opdivo

Nivolumab and ADG106

ADG106 DRUG

Administered as an intravenous infusion over 90 minutes.

Nivolumab and ADG106

Eligibility Criteria

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

You may qualify if:

• For Phase 1b: Patients with histologically or cytologically confirmed solid malignancies
• who are refractory to standard of care treatment OR
• have no standard of care treatment of curative potential.
• For Phase 2: Patients with histologically or cytologically confirmed stage 4 or recurrent NSCLC (per IASLC classification) who have progression of disease
• after treatment with antiPD1/PDL1 with CTLA4 inhibitors and at least one platinum-based chemotherapy OR
• after treatment with antiPD1/PDL1 without CTLA4 inhibitors and at least one platinum-based chemotherapy
• The participant (or legally acceptable representative if applicable) provides written consent for the trial.
• Participants who are at least 21 years of age on the day of signing informed consent.
• Eastern Cooperative Group (ECOG) Performance Status 0-1
• Measurable disease according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1). Previously irradiated lesions is considered measurable if they show progression after completion of radiation therapy.
• Have adequate organ function. Specimens must be collected within 7 days prior to the start of study treatment.
• A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies:
• Not a woman of childbearing potential OR
• A woman of childbearing potential who agrees to follow the contraceptive guidance during the treatment period and for at least 120 days after the last dose of study medication.
• A male participant must agree to use a contraception during the treatment period and for at least 120 days after the last dose of study treatment and refrain from donating sperm during this period.

You may not qualify if:

• Has received prior systemic anti-cancer therapy including investigational agents within 3 weeks prior to enrolment.
• Note: Participants must have recovered from all AEs to previous therapies to ≤ Grade 1 or baseline. Participants with ≤ Grade 2 neuropathy may be eligible. Note: If participants received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting study treatment.
• Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to first dose of study treatment.
• Note: Participants who have entered the follow-up phase of an investigational study may participate as long as it has been 4 weeks after the last dose of the previous investigational agent.
• Prior severe immune adverse events of grade 3 or 4 to antiPD1/PDL1 therapy. These include interstitial pneumonitis.
• Has a known history of active TB (Mycobacterium tuberculosis).
• Known allergy to any of the ingredients of ADG106 (succinic acid, arginine, polysorbate 80 and hydrochloric acid) in the formulation or known allergy to any related class of compounds (note: polysorbate 80 is an ingredient in docetaxel).
• Has received prior radiotherapy within 2 weeks of start of study treatment. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (≤ 2 weeks of radiotherapy) to non-CNS disease.
• Has a known additional malignancy that is progressing or has required active treatment within the past 3 years.
• Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, transitional cell carcinoma of urothelial cancer, or carcinoma in situ (e.g. breast or cervical carcinoma in situ) that have undergone potentially curative therapy are not excluded.
• Known brain metastases or leptomeningeal metastases that are not adequately treated and require corticosteroids of \> 10mg daily prednisolone or its equivalent at least 7 days prior to study treatment start date.
• Has an active infection requiring systemic therapy.
• History of having received a live virus vaccination (eg yellow fever, MMR, nasal flu, chicken pox or Zostavax) in the past 1 month.
• Subjects with underlying hemoglobinopathies (e.g., thalassemia).
• Subjects with an active, known or suspected autoimmune disease. Subjects with type I diabetes mellitus, hypothyroidism only requiring hormone replacement, skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll.

Sponsors & Collaborators

• National University Hospital, Singapore: lead
• Adagene Inc: collaborator
• Bristol-Myers Squibb: collaborator
• Singapore Translational Cancer Consortium: collaborator

Study Sites (2)

National Cancer Centre Singapore

Singapore, 169610, Singapore

NOT YET RECRUITING

National University Hospital

Singapore, Singapore

RECRUITING

Related Publications (4)

• Sanchez-Paulete AR, Labiano S, Rodriguez-Ruiz ME, Azpilikueta A, Etxeberria I, Bolanos E, Lang V, Rodriguez M, Aznar MA, Jure-Kunkel M, Melero I. Deciphering CD137 (4-1BB) signaling in T-cell costimulation for translation into successful cancer immunotherapy. Eur J Immunol. 2016 Mar;46(3):513-22. doi: 10.1002/eji.201445388. Epub 2016 Feb 9.

  PMID: 26773716 RESULT

• Costantini A, Corny J, Fallet V, Renet S, Friard S, Chouaid C, Duchemann B, Giroux-Leprieur E, Taillade L, Doucet L, Nguenang M, Jouveshomme S, Wislez M, Tredaniel J, Cadranel J. Efficacy of next treatment received after nivolumab progression in patients with advanced nonsmall cell lung cancer. ERJ Open Res. 2018 Apr 20;4(2):00120-2017. doi: 10.1183/23120541.00120-2017. eCollection 2018 Apr.

  PMID: 29692997 RESULT

• Freeman AT, Lesperance M, Wai ES, Croteau NS, Fiorino L, Geller G, Brooks EG, Poonja Z, Fenton D, Irons S, Ksienski D. Treatment of non-small-cell lung cancer after progression on nivolumab or pembrolizumab. Curr Oncol. 2020 Apr;27(2):76-82. doi: 10.3747/co.27.5495. Epub 2020 May 1.

  PMID: 32489249 RESULT

• Qi X, Li F, Wu Y, Cheng C, Han P, Wang J, Yang X. Optimization of 4-1BB antibody for cancer immunotherapy by balancing agonistic strength with FcgammaR affinity. Nat Commun. 2019 May 20;10(1):2141. doi: 10.1038/s41467-019-10088-1.

  PMID: 31105267 RESULT

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

Nivolumab

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

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

Study Officials

• Boon Cher Goh

  National University Hospital, Singapore

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Boon Cher Goh

CONTACT

+65 6772 4617; boon_cher_goh@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

Study Record Dates

• First Submitted: October 11, 2021
• First Posted: February 11, 2022
• Study Start: November 12, 2021
• Primary Completion: May 1, 2024
• Study Completion: May 1, 2024
• Last Updated: March 25, 2022

Record last verified: 2022-03

Data Sharing

• IPD Sharing: Will not share

Locations

SG (2)