NCT03921879

A Phase 1 Study of OT-82 in Patients With Relapsed or Refractory Lymphoma

Status unknown Phase 1 Last updated 22 October 2020

What this trial tests

Phase 1 trial testing OT-82 Dose Escalation in Lymphoma in 50 participants. Status unknown.

Timeline

29 July 2019

Primary endpoint
1 April 2021

1 June 2021

Quick facts

Lead sponsor	Oncotartis, Inc.
Phase	Phase 1
Status	Status unknown
Study type	INTERVENTIONAL
Allocation	non randomized
Design	parallel
Masking	none
Primary purpose	treatment
Enrollment	50
Start date	29 July 2019
Primary completion	1 April 2021
Estimated completion	1 June 2021
Sites	8 locations across United States

Drugs / interventions tested

• OT-82 Dose Escalation — full drug profile →
• OT-82 Dose Expansion — full drug profile →

Conditions studied

• Lymphoma — all drugs for Lymphoma →
• Lymphoma, Non-Hodgkin — all drugs for Lymphoma, Non-Hodgkin →
• Lymphoma, B-Cell — all drugs for Lymphoma, B-Cell →
• Lymphoma, T-Cell — all drugs for Lymphoma, T-Cell →

Sponsor

Oncotartis, Inc. — full company profile →

Who can join

18 and older, any sex, with Lymphoma or Lymphoma, Non-Hodgkin. Patients with the condition only — healthy volunteers not accepted.

What's being measured

Primary outcomes are the specific endpoints the trial is designed to prove or disprove.

• Occurence of Dose Limiting Toxicities (DLT) in all participants during the Stage 1 Dose Escalation period
  Time frame: C1 (Days 1-28) through study completion.
  A DLT is a defined Adverse Events (AE) that limits the dosing schedule occurring during Cycle 1 regardless of Investigator attribution to OT-82.
• Overall Response Rate in Participants with R/R Lymphoma
  Time frame: During Screening, at the end of Cycle 2 (C2) [each cycle is 28 days], then every 2 cycles thereafter until development of Progressive Disease (PD) up to week 24.
  Evaluation of antitumor response in patients with lymphoma will be by the Lugano Classification criteria for malignant lymphoma. Participant with undergo Computed Tomography (CT) scans or Magnetic Resonance Imaging (MRI) scans for participants unable to have CT imaging. Overall response is derived from time-point response assessments as follows: * CR: Complete disappearance of all detectible clin
• Response to OT-82 in Participants with Skin Involvement
  Time frame: Baseline (-14 days to -1 day before treatment), at the end of C1 and C2 (each cycle is 28 days), and every 2 cycles thereafter up to week 24.
  Assessments will be made using the modified Severity Weighted Assessment Tool (mSWAT) and will include skin biopsies and/or photographs as indicated.
• Response to OT-82 in Participants with Bone Marrow Involvement
  Time frame: Baseline (-14 days to -1 day before treatment) and at week 24.
  Bone marrow studies will be performed to confirm CR in patients with known bone marrow involvement. Bone marrow aspirates (±biopsy) will be assessed.
• Response to OT-82 in Participants with PTCL and known circulating clonal T lymphocytes
  Time frame: Baseline (-14 days to -1 day before treatment), at the end of C1 and C2 (each cycle is 28 days), and every 2 cycles thereafter up to week 24.
  Relevant clonal T cell populations will be measured from peripheral blood samples during treatment with OT-82 and compared to baseline measures.

Sponsor's own description

This research study will test OT-82, which is an investigational ("research" or "experimental" ) drug. The study has two stages (Stage 1 and Stage 2). The purpose of Stage 1 is to determine the safety and tolerability and the maximum tolerated dose (MTD) or the maximum tested dose of OT-82 administered orally to participants. The purpose of Stage 2 is to determine the preliminary efficacy of OT-82 in relapsed or refractory lymphoma at the MTD or the maximum tested dose. Both parts of the study will also evaluate the pharmacokinetics (absorption, distribution, metabolism, elimination) of OT-82.

OT-82 treatment slowed the growth, reduced the size, or in some cases cured certain cancers in animal studies. It is hoped that participants with relapsed or refractory lymphoma treated with OT - 82 in this study will experience slowing tumor growth and/or reduction of tumor size.

Publications & conference data

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

1. NAD⁺ metabolism, stemness, the immune response, and cancer.
   Navas LE, Carnero A. · · 2021 · cited 379× · PMID 33384409 · DOI 10.1038/s41392-020-00354-w
2. Recent Advances in NAMPT Inhibitors: A Novel Immunotherapic Strategy.
   Galli U, Colombo G, Travelli C, Tron GC, et al · · 2020 · cited 122× · PMID 32477131 · DOI 10.3389/fphar.2020.00656
3. Beyond Energy Metabolism: Exploiting the Additional Roles of NAMPT for Cancer Therapy.
   Heske CM. · · 2019 · cited 80× · PMID 32010616 · DOI 10.3389/fonc.2019.01514
4. Review of various NAMPT inhibitors for the treatment of cancer.
   Wei Y, Xiang H, Zhang W. · · 2022 · cited 74× · PMID 36160449 · DOI 10.3389/fphar.2022.970553
5. Advances in NAD-Lowering Agents for Cancer Treatment.
   Ghanem MS, Monacelli F, Nencioni A. · · 2021 · cited 46× · PMID 34068917 · DOI 10.3390/nu13051665
6. Nicotinamide Adenine Dinucleotide (NAD) Metabolism as a Relevant Target in Cancer.
   Navas LE, Carnero A. · · 2022 · cited 42× · PMID 36078035 · DOI 10.3390/cells11172627
7. Inhibition of nicotinamide phosphoribosyltransferase (NAMPT) with OT-82 induces DNA damage, cell death, and suppression of tumor growth in preclinical models of Ewing sarcoma.
   Gibson AE, Yeung C, Issaq SH, Collins VJ, et al · · 2020 · cited 23× · PMID 32908120 · DOI 10.1038/s41389-020-00264-0
8. Targeting NAD⁺ metabolism: dual roles in cancer treatment.
   Yong J, Cai S, Zeng Z. · · 2023 · cited 16× · PMID 38116009 · DOI 10.3389/fimmu.2023.1269896