TumorPhase 1NCT05470283
Phase I, Open-Label, Study of Tumor Infiltrating Lymphocytes Engineered With Membrane Bound IL15 Plus Acetazolamide in Adult Patients With Metastatic Melanoma
A Phase 1 study testing OBX-115, Acetazolamide and Cyclophosphamide in people with Tumor and Metastatic Melanoma, run by M.D. Anderson Cancer Center at 1 site in United States.
Trial summary
The goal of this clinical research study is to find the recommended dose of OBX-115 in combination with acetazolamide that can be given to patients with metastatic melanoma previously treated with immune checkpoint inhibitors. The safety and tolerability of the study drug combination will also be studied. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Tumor, Metastatic Melanoma, Melanoma
- What is being tested?
- OBX-115, Acetazolamide and Cyclophosphamide
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 21 participants
- Where
- 1 siteUnited States
- Study dates
- 7 Sep 2022to 1 Apr 2027
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male or female patients age ≥ 18 at the time of signing ICF
- Patient has a pathologically confirmed diagnosis of metastatic melanoma that is unresectable stage III or stage IV and has lesion(s) amenable to resection for the generation of TILs and at least one separate lesion for RECIST v1.1 response assessment
- Patient must be relapsed and/or refractory to immune checkpoint inhibitor (ICI) therapy including either anti PD-1 either with or without anti CTLA-4 blocking antibody and/or anti LAG-3 antibody. Patients should have received standard-of-care (SOC) therapy per standard clinical practice guidelines. Patients must not have had exposure to more than 3 prior lines of anti-PD-1 antibody-containing therapeutic regimens administered in the metastatic setting If the patient is BRAF V600 mutation-positive with rapidly progressing disease, the patient should have received available FDA-approved targeted therapy.
- ECOG Performance status 0-1
- Within 7 days of tumor harvest and within 7 days of initiating lymphodepletion, patients must meet the following laboratory criteria:
- Absolute neutrophil count (ANC) ≥ 1000/mm3
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- Hemoglobin ≥ 8.0 g/dL (transfusion allowed)
- Platelet count ≥ 75,000/mm3
- ALT/SGPT and AST/SGOT ≤ 2.5 x the upper limit of normal (ULN)
- Patients with liver metastases may have liver function tests (LFT) ≤ 5.0 x ULN
- Calculated creatinine clearance (Cockcroft-Gault) ≥ 50.0 mL/min
- Total bilirubin ≤ 1.5 X ULN
- Negative serum pregnancy test (female patients of childbearing potential)
- Patients must have a 12-lead electrocardiogram (EKG) showing no active ischemia and Fridericia's corrected QT interval (QTcF) less than 480 ms
- Patients must have echocardiogram showing no evidence of congestive heart failure (as defined by New York Heart Association Functional Classification III or IV) or LVEF <50%
- Women of child-bearing potential (WCBP), defined as a sexually mature woman who has not undergone a hysterectomy or tubal ligation or who has not been naturally postmenopausal for at least 24 consecutive months, must have a negative serum pregnancy test prior to treatment. All sexually active WCBP and all sexually active male patients must agree to use effective methods of birth control throughout the study. Approved methods of birth control are as follows:
- Hormonal contraception (i.e. birth control pills, injection, implant, transdermal patch, vaginal ring),
- Intrauterine device (IUD),
- Tubal Ligation or hysterectomy,
- Subject/partner status post vasectomy,
- Implantable or injectable contraceptives, and
- Condoms plus spermicide.
- Patient (or legally authorized representative) has voluntarily agreed to participate in the study by providing signed and dated informed consent (ICF) in accordance with International Conference on Harmonization (ICH) Good Clinical Practice (GCP) guidelines and applicable local regulations
- Patient has agreed to abide by all protocol required procedures including study related assessments, and management by treating institution for the duration of the study and long-term follow-up (LTFU)
- Patients who have received bridging therapy between time of TIL harvest and initiation of lymphodepletion must meet all required clinical, laboratory and imaging criteria in order to qualify for therapy initiation
- Lesions amenable to radiotherapy or palliative radiotherapy (e.g.- bone metastases or metastases causing nerve impingement) should be treated > 4 weeks prior to enrollment and subjects must be fully recovered from the effects of radiation. However, palliative radiation is permitted if subjects recover from all side effects to ≤ Grade 1 toxicities (based on CTCAE, v.5) and is > 2 weeks prior to starting lymphodepletion.
Who cannot join
- Patients with uncontrolled intercurrent medical illnesses, including active systemic infection, coagulation disorders or major cardiovascular, respiratory or immune diseases. PI or his/her designee shall make the final determination regarding appropriateness of enrollment
- Patients on chronic steroid therapy for primary immunodeficiency; however, prednisone or its equivalent is allowed at ≤ 10 mg/day
- Patients who are pregnant or breastfeeding
- Chemotherapy within 2 weeks prior to TIL harvest
- Treatment with small molecule targeted antineoplastics and chemotherapy within 2 weeks of initiation of lymphodepletion, or 5 half-lives, whichever is shorter
- The use of immune checkpoint inhibitors as bridging therapy is not allowed.
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- Patients who have received live vaccines within 30 days prior to TIL harvest and initiation of lymphodepletion
- Patients with active infection requiring systemic therapy or causing fever (temperature > 38.1oC) or patients with unexplained fever (temperature > 38.1oC) within 7 days prior to day of investigational product administration
- Patient has active infection with human immunodeficiency virus (HIV), hepatitis B virus, hepatitis C virus (HCV) requiring active antiviral therapy.
- Cytomegalovirus (CMV) IgM antibody titer or PCR assay; and Epstein-Barr virus (EBV) IgM or PCR assay indicating active infection. Tumor harvest may take place even with positive results as long as consult with infectious disease physician is planned and the infection can be appropriately treated, if needed, prior to initiation of lymphodepletion.
- Positive herpes simplex virus (HSV)-1 serology or PCR assay • Patients who are HSV PCR assay positive will need to receive appropriate treatment and become PCR assay negative prior to starting the lymphodepletion Tumor harvest may take place even with positive results as long as consult with infectious disease physician is planned and the infection can be appropriately treated, if needed, prior to initiation of lymphodepletion.
- Persistent prior therapy-related toxicities greater than Grade 2 according to Common Toxicity Criteria for Adverse Events (CTCAE) v5.0, except for peripheral neuropathy, alopecia, or vitiligo prior to enrollment. Patients with prior immune mediated hypophysitis or adrenal insufficiency or hypothyroidism are eligible for treatment as long as they are on stable, physiologic doses of hormone repletion.
- History of organ or hematopoietic stem cell transplant
- History of clinically significant autoimmune disease
- The following are exceptions to the criterion:
- Patients with vitiligo or alopecia.
- Patients with hypothyroidism, type 1 diabetes or adrenal insufficiency stable on hormone replacement therapy.
- Patients without active disease in the last 5 years may be included but only after consultation with the PI.
- Any other history or questionable history of autoimmune disease is to be considered after consultation with the PI
- 15. History of central nervous system metastases and/or leptomeningeal spread of melanoma.
- 16. Patients with significant clinical cardiac abnormalities:
- Left ventricular ejection fraction (LVEF) <50%
- congestive heart failure, defined by New York Heart Association Functional Classification III or IV
- unstable angina
- serious uncontrolled cardiac arrhythmia
- a myocardial infarction within 6 months prior to study entry or a history of myocarditis
- 17. Patients with a history of interstitial lung disease
- 18. History of a concurrent second malignancy (diagnosed in the last 2 years). Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin, localized thyroid cancer or in situ cervical cancer that has undergone potentially curative therapy.
- 19. Patients unable to provide informed consent and follow the study procedures (e.g., due to language problems, psychological disorders, dementia).
- 20. Documented severe/life threatening sulfa allergy.
- 21. Chronic need for acetazolamide or other carbonic anhydrase inhibitors
Trial locations and contacts
1 site in 1 country.
About this study
The goal of this clinical research study is to find the recommended dose of OBX-115 in combination with acetazolamide that can be given to patients with metastatic melanoma previously treated with immune checkpoint inhibitors. The safety and tolerability of the study drug combination will also be studied.
Read the detailed description
Primary Objective:
- Assess the safety and tolerability of OBX-115 + acetazolamide by CTCAE version 5 criteria to provide a recommended Phase II dose
Secondary Objectives:
- Assess preliminary efficacy of OBX-115 + acetazolamide cell therapy in patients with immune checkpoint inhibitor (ICI)-relapsed and/or refractory metastatic melanoma by evaluating overall response rate (ORR; complete response [CR] + partial response [PR]) by RECIST 1.1 criteria
- Evaluate feasibility of the manufacturing process
- Evaluate duration of response (DOR)
- Evaluate progression free survival (PFS)
- Characterize in vivo cellular kinetics of OBX-115 cells in tumor and/or in peripheral blood by polymerase chain (PCR) and/or fluorescence-activated cell sorting (FACS) analyses
- Characterize the pharmacokinetic profile of acetazolamide when administered in combination with OBX-115
- Characterize the incidence and prevalence of OBX-115 therapy immunogenicity
Exploratory Objectives:
- Assess relationship of soluble immune factors and pharmacodynamic markers, with cellular kinetics, safety, and efficacy
- Describe the composition of OBX-115 subsets (immunophenotyping in peripheral blood mononuclear cells [PBMCs] and in tumor), summarized by clinical response
- Explore the correlation of OBX-115 kinetics in tumor and peripheral blood with clinical endpoints
- Explore the correlation of immune checkpoints with OBX-115 cellular kinetics and efficacy
- Evaluate overall survival (OS)
- Conditions
- Tumor, Metastatic Melanoma, Melanoma
- Being tested
- OBX-115, Acetazolamide, Cyclophosphamide, Furosemide, Mesna
- Medical subject headings
- Neoplasms, Melanoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
OBX-115Drug
Given by IV
AcetazolamideDrug
Given by PO
CyclophosphamideDrug
Also called Cytoxan®, Neosar
Given by IV
FurosemideDrug
Given by IV
MesnaDrug
Given by IV
Also called Fludarabine, Fludara
Given by IV
| Study group | Role | What they receive |
|---|---|---|
| OBX-115 plus Acetazolamide | Experimental | Participants will receive chemotherapy to prepare your body for the study drug combination, then you will receive OBX-115 and acetazolamide. Receives: Drug: OBX-115; Drug: Acetazolamide; Drug: Cyclophosphamide; Drug: Furosemide; Drug: Mesna; Drug: Fludarabine Phosphate |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence and nature of dose-limiting toxicities (DLTs) during the first 28 days after OBX-115 + acetazolamide administration as assessed by CTCAE version 5.0. Incidence and severity of AEs and SAEs after OBX-115 + acetazolamide administration.
Measured: through completion of study, an average of 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Jul 2022
- Study start7 Sep 2022
- Primary completion1 Apr 2027 (estimated)
- Study completion1 Apr 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for TumorStudies of the same condition, open and under way.
- More trials run by M.D. Anderson Cancer CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 21 participants (actual)
Sponsor and investigators
- Lead sponsor
- M.D. Anderson Cancer Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Rodabe N Amaria, MD, Principal investigator, M.D. Anderson Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05470283
- Sponsor's protocol ID
- 2022-0356
- Other IDs
- NCI-2022-06873
- Status last verified
- Oct 2026
- First submitted
- 20 Jul 2022
- Last updated
- 7 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Amaria RN, Chesney JA, Betof AS, In GK, Shoushtari AN, Johnson TT, Hamid O, Samhouri Y, Davies MA, Tawbi HA, Glitza Oliva IC, Aksoy BA, Kelly AM, Duan R, Prabhakar P, Ramsingh G, Jagasia M, Hari P. Regulatable membrane-bound IL-15 engineered TIL cell therapy for immune checkpoint inhibitor-resistant advanced melanoma: pooled analysis of phase 1 and 1/2 trials. Nat Med. 2026 Nov 3. doi: 10.1038/s41591-026-04743-6. Online ahead of print.
PubMed 42977756
Study at a glance
From the registry record, last updated by the sponsor on 7 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I, Open-Label, Study of Tumor Infiltrating Lymphocytes Engineered With Membrane Bound IL15 Plus Acetazolamide in Adult Patients With Metastatic Melanoma
- ClinicalTrials.gov ID
- NCT05470283
- Acronym / sponsor ID
- 2022-0356
- Conditions
- Tumor, Metastatic Melanoma, Melanoma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 21 participants (actual)
- Lead sponsor
- M.D. Anderson Cancer CenterUniversity, hospital or other
- Study start
- 7 Sep 2022 (actual)
- Primary completion
- 1 Apr 2027 (estimated)
- Study completion
- 1 Apr 2027 (estimated)
- First posted
- 22 Jul 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The goal of this clinical research study is to find the recommended dose of OBX-115 in combination with acetazolamide that can be given to patients with metastatic melanoma previously treated with immune checkpoint inhibitors. The safety and tolerability of the study drug combination will also be studied.
Detailed description
Primary Objective:
- Assess the safety and tolerability of OBX-115 + acetazolamide by CTCAE version 5 criteria to provide a recommended Phase II dose
Secondary Objectives:
- Assess preliminary efficacy of OBX-115 + acetazolamide cell therapy in patients with immune checkpoint inhibitor (ICI)-relapsed and/or refractory metastatic melanoma by evaluating overall response rate (ORR; complete response [CR] + partial response [PR]) by RECIST 1.1 criteria
- Evaluate feasibility of the manufacturing process
- Evaluate duration of response (DOR)
- Evaluate progression free survival (PFS)
- Characterize in vivo cellular kinetics of OBX-115 cells in tumor and/or in peripheral blood by polymerase chain (PCR) and/or fluorescence-activated cell sorting (FACS) analyses
- Characterize the pharmacokinetic profile of acetazolamide when administered in combination with OBX-115
- Characterize the incidence and prevalence of OBX-115 therapy immunogenicity
Exploratory Objectives:
- Assess relationship of soluble immune factors and pharmacodynamic markers, with cellular kinetics, safety, and efficacy
- Describe the composition of OBX-115 subsets (immunophenotyping in peripheral blood mononuclear cells [PBMCs] and in tumor), summarized by clinical response
- Explore the correlation of OBX-115 kinetics in tumor and peripheral blood with clinical endpoints
- Explore the correlation of immune checkpoints with OBX-115 cellular kinetics and efficacy
- Evaluate overall survival (OS)
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| OBX-115 plus Acetazolamide | Experimental | Drug: OBX-115, Drug: Acetazolamide, Drug: Cyclophosphamide, Drug: Furosemide, Drug: Mesna, Drug: Fludarabine PhosphateParticipants will receive chemotherapy to prepare your body for the study drug combination, then you will receive OBX-115 and acetazolamide. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (26 listed)
- Male or female patients age ≥ 18 at the time of signing ICF
- Patient has a pathologically confirmed diagnosis of metastatic melanoma that is unresectable stage III or stage IV and has lesion(s) amenable to resection for the generation of TILs and at least one separate lesion for RECIST v1.1 response assessment
- Patient must be relapsed and/or refractory to immune checkpoint inhibitor (ICI) therapy including either anti PD-1 either with or without anti CTLA-4 blocking antibody and/or anti LAG-3 antibody. Patients should have received standard-of-care (SOC) therapy per standard clinical practice guidelines. Patients must not have had exposure to more than 3 prior lines of anti-PD-1 antibody-containing therapeutic regimens administered in the metastatic setting If the patient is BRAF V600 mutation-positive with rapidly progressing disease, the patient should have received available FDA-approved targeted therapy.
- ECOG Performance status 0-1
- Within 7 days of tumor harvest and within 7 days of initiating lymphodepletion, patients must meet the following laboratory criteria:
Key exclusion criteria (31 listed)
- Patients with uncontrolled intercurrent medical illnesses, including active systemic infection, coagulation disorders or major cardiovascular, respiratory or immune diseases. PI or his/her designee shall make the final determination regarding appropriateness of enrollment
- Patients on chronic steroid therapy for primary immunodeficiency; however, prednisone or its equivalent is allowed at ≤ 10 mg/day
- Patients who are pregnant or breastfeeding
- Chemotherapy within 2 weeks prior to TIL harvest
- Treatment with small molecule targeted antineoplastics and chemotherapy within 2 weeks of initiation of lymphodepletion, or 5 half-lives, whichever is shorter
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| OBX-115Given by IV | Drug | OBX-115 plus Acetazolamide |
| AcetazolamideGiven by PO | Drug | OBX-115 plus Acetazolamide |
| CyclophosphamideAlso: Cytoxan®, NeosarGiven by IV | Drug | OBX-115 plus Acetazolamide |
| FurosemideGiven by IV | Drug | OBX-115 plus Acetazolamide |
| MesnaGiven by IV | Drug | OBX-115 plus Acetazolamide |
| Fludarabine PhosphateAlso: Fludarabine, FludaraGiven by IV | Drug | OBX-115 plus Acetazolamide |
Primary outcome
Incidence and nature of dose-limiting toxicities (DLTs) during the first 28 days after OBX-115 + acetazolamide administration as assessed by CTCAE version 5.0. Incidence and severity of AEs and SAEs after OBX-115 + acetazolamide administration.
Time frame: through completion of study, an average of 1 year
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Oct 2026.
- Derived from this study: PubMed 42977756Amaria RN, Chesney JA, Betof AS, In GK, Shoushtari AN, Johnson TT, Hamid O, Samhouri Y, Davies MA, Tawbi HA, Glitza Oliva IC, Aksoy BA, Kelly AM, Duan R, Prabhakar P, Ramsingh G, Jagasia M, Hari P. Regulatable membrane-bound IL-15 engineered TIL cell therapy for immune checkpoint inhibitor-resistant advanced melanoma: pooled analysis of phase 1 and 1/2 trials. Nat Med. 2026 Nov 3. doi: 10.1038/s41591-026-04743-6. Online ahead of print.
- M D Anderson Cancer CenterLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Rodabe N Amaria, MD principal investigator
M.D. Anderson Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing OBX-115, Acetazolamide and Cyclophosphamide in people with Tumor and Metastatic Melanoma, run by M.D. Anderson Cancer Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 26 inclusion and 31 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 7 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence and nature of dose-limiting toxicities (DLTs) during the first 28 days after OBX-115 + acetazolamide administration as assessed by CTCAE version 5.0. Incidence and severity of AEs and SAEs after OBX-115 + acetazolamide administration. (time frame: through completion of study, an average of 1 year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05470283, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Oct 2026.