Unresectable MelanomaPhase 1/2NCT05361174
A Study to Investigate the Efficacy and Safety of an Infusion of IOV-4001 in Adult Participants With Unresectable or Metastatic Melanoma or Stage III or IV Non-small-cell Lung Cancer
A Phase 1/2 study testing IOV-4001 in people with Unresectable Melanoma and Metastatic Melanoma, run by Iovance Biotherapeutics, Inc. at 11 sites in United States.
Trial summary
This is a study to investigate the efficacy and safety of an infusion of IOV-4001 in adult participants with unresectable or metastatic melanoma or advanced non-small-cell lung cancer (NSCLC). Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Unresectable Melanoma, Metastatic Melanoma, Stage III Non-small Cell Lung Cancer
- What is being tested?
- IOV-4001
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 53 participants
- Where
- 11 sitesUnited States
- Study dates
- 20 Jul 2022to Sep 2029
- Phase
- Phase 1/2
- 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 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Participants must have a confirmed diagnosis of Stage IIIC, IIID, or IV unresectable or metastatic melanoma or Stage III or IV NSCLC.
- Participants who have received the following previous therapy:
- Cohort 1 (Melanoma): Participants who have progressed within 12 weeks of last dose of anti-PD-1/PD-L1 blocking antibody and received BRAF/MEK inhibitor in those with BRAF mutations.
- Cohort 2 (NSCLC): Participants who should have received no more than 3 prior lines of therapy and:
- those without oncogene-driven tumors: Have progressed within 12 weeks after last dose of anti-PD-1/PD-L1 blocking antibody
- those with oncogene-driven tumors: Have progressed during/after ≥1 targeted therapy AND either:
Show all 16Show fewer
- platinum doublet chemotherapy
- Or within 12 weeks after last dose of anti-PD-1/PD-L1 blocking antibody
- Participants who have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
- Participants who is assessed as having at least one resectable lesion.
- Participants who have at least one measurable lesion, following resection of the lesion for IOV-4001 generation.
- Participants who have adequate organ function.
- Cardiac function test required.
- Pulmonary function test may be required.
- Participants of childbearing potential or those with partners of childbearing potential must be willing to practice an approved method of highly effective birth control during treatment and up to 12 months.
- Participants who are >70 years of age may be allowed to enroll after the investigator discusses with the medical monitor.
Who cannot join
- Participants who have melanoma of uveal/ocular origin.
- Participants who have symptomatic untreated brain metastases.
- Participants who have had a history of allogeneic organ transplant or any form of cell therapy involving prior conditioning chemotherapy within the past 20 years.
- Participants who require systemic steroid therapy 10 mg/day prednisone or another steroid equivalent dose.
- Participants who have any form of primary immunodeficiency.
- Participants who have another primary malignancy within the previous 3 years.
- Participants who have received or will receive a live or attenuated vaccination within 28 days prior to the start of the NMA-LD.
Trial locations and contacts
11 sites in 1 country. Contact the study team or a site near you to ask about taking part.
11 sites in 1 country
United States11 sites, 10 recruiting
- Recruiting
University of Cincinnati
Cincinnati, Ohio, 45219
- Recruiting
The Angeles Clinic and Research Institute
Los Angeles, California, 90025
- Recruiting
University of Louisville
Louisville, Kentucky, 40202
- Recruiting
Sylvester Comprehensive Cancer Center
Miami, Florida, 33136
- Withdrawn
Medical College of Wisconsin
Milwaukee, Wisconsin, 53226
- Recruiting
Weill Medical College of Cornell University
New York, New York, 10022
- Recruiting
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
- Recruiting
Orlando Health Cancer Institute
Orlando, Florida, 32610
- Recruiting
UPMC Hillman Cancer Center
Pittsburgh, Pennsylvania, 15232
- Recruiting
Moffitt Cancer Center
Tampa, Florida, 33612
- Recruiting
The University of Kansas Cancer Center
Westwood, Kansas, 66205
About this study
Official title: A Phase 1/2, Open-label Study of PD-1 Knockout Tumor-infiltrating Lymphocytes (IOV-4001) in Participants With Unresectable or Metastatic Melanoma or Stage III or IV Non-small-cell Lung Cancer
This is a study to investigate the efficacy and safety of an infusion of IOV-4001 in adult participants with unresectable or metastatic melanoma or advanced non-small-cell lung cancer (NSCLC).
Read the detailed description
This study is the first-in-human study of IOV-4001, a genetically modified autologous tumor- infiltrating lymphocytes (TIL) product. IOV-4001 is expected to have antitumor activity through its capacity to directly target and kill tumor cells in a manner that is similar to non-genome-edited TIL, but with the potential for enhanced antitumor activity due to disruption of PDCD1, the gene for programmed cell death protein-1 (PD-1).
- Conditions
- Unresectable Melanoma, Metastatic Melanoma, Stage III Non-small Cell Lung Cancer, Stage IV Non-small Cell Lung Cancer
- Being tested
- IOV-4001
- Keywords
- Tumor Infiltrating Lymphocytes, TIL, Unresectable Melanoma, Metastatic Melanoma, Stage III Non-small-cell lung cancer, Stage IV Non-small-cell lung cancer, PD-1 Knockout, Cell Therapy, Autologous Adoptive Cell Therapy, Cellular Immuno-therapy, IL-2, Non Small Cell Lung Cancer, NSCLC, Second line Lung Cancer, Bronchial Neoplasms, Carcinoma, Lung Disease, Metastatic Lung Cancer, Metastatic Non Small Cell Lung Cancer, Lung Carcinoma
- Medical subject headings
- Melanoma, Carcinoma, Non-Small-Cell Lung, Bronchial Neoplasms, Carcinoma, Lung Diseases, Lung Neoplasms, Neoplasms, Skin Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IOV-4001Biological
A tumor sample is resected from each participant and cultured ex-vivo to manufacture IOV-4001. After lymphodepleting chemotherapy including cyclophosphamide and fludarabine, participant is infused with IOV-4001, and followed by IL-2.
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1 | Experimental | Participants with unresectable or metastatic melanoma Receives: Biological: IOV-4001 |
| Cohort 2 | Experimental | Participants with Stage III or IV non-small-cell lung cancer Receives: Biological: IOV-4001 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Phase I: Safety of IOV-4001
The safety of IOV-4001 will be assessed based on the totality of dose-limiting toxicity (DLT) and adverse event (AE) data collected during this phase
Measured: Up to 1 Year or depending on when the recommended phase 2 dose is determined
Phase 2: Objective Response Rate (ORR)
To evaluate the proportion of participants who have a confirmed complete response (CR) or partial response (PR) per RECIST v1.1 as assessed by the investigator
Measured: Up to 60 months
Secondary outcomes (7)
CR Rate
To evaluate the proportion of participants who have a confirmed CR per RECIST v1.1 as assessed by the investigator
Measured: Up to 60 months
Duration of Response (DOR)
To evaluate the duration from the time that criteria are met for CR or PR per RECIST v1.1 as assessed by the investigator until disease progression or death due to any cause
Measured: Up to 60 months
Disease Control Rate (DCR)
To evaluate the percentage of participants with a best overall confirmed response of CR or PR at any time plus stable disease (SD) per RECIST v1.1 as assessed by the investigator
Measured: Up to 60 months
Progression-free Survival (PFS)
To evaluate the time from the date of IOV-4001 infusion until disease progression per RECIST v1.1 as assessed by the investigator or death due to any cause
Measured: Up to 60 months
Overall Survival (OS)
To evaluate the time from the date of IOV-4001 infusion to death due to any cause.
Measured: Up to 60 months
Safety and Tolerability of IOV-4001
This will be characterized by the severity, seriousness, relationship to study treatment, and characteristics of treatment-emergent adverse events (TEAEs).
Measured: Up to 60 months
Feasibility of IOV-4001
This will be assessed by the proportion of participants who had tumor harvested and were treated without manufacturing delay or failure.
Measured: Up to 60 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 May 2022
- Study start20 Jul 2022
- Primary completionSep 2027 (estimated)
- Study completionSep 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Unresectable MelanomaStudies of the same condition, open and under way.
- 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 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 53 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Iovance Biotherapeutics, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Iovance Biotherapeutics Study Team, Study director, Iovance Biotherapeutics
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05361174
- Sponsor's protocol ID
- IOV-GM1-201
- Status last verified
- Jun 2026
- First submitted
- 29 Apr 2022
- Last updated
- 11 Jun 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 11 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1/2, Open-label Study of PD-1 Knockout Tumor-infiltrating Lymphocytes (IOV-4001) in Participants With Unresectable or Metastatic Melanoma or Stage III or IV Non-small-cell Lung Cancer
- ClinicalTrials.gov ID
- NCT05361174
- Acronym / sponsor ID
- IOV-GM1-201
- Conditions
- Unresectable Melanoma, Metastatic Melanoma, Stage III Non-small Cell Lung Cancer, Stage IV Non-small Cell Lung Cancer
- Keywords
- Tumor Infiltrating Lymphocytes, TIL, Unresectable Melanoma, Metastatic Melanoma, Stage III Non-small-cell lung cancer, Stage IV Non-small-cell lung cancer, PD-1 Knockout, Cell Therapy
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 53 participants (estimated)
- Lead sponsor
- Iovance Biotherapeutics, Inc.Industry (pharma, biotech, devices)
- Study start
- 20 Jul 2022 (actual)
- Primary completion
- Sep 2027 (estimated)
- Study completion
- Sep 2029 (estimated)
- First posted
- 4 May 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.
This is a study to investigate the efficacy and safety of an infusion of IOV-4001 in adult participants with unresectable or metastatic melanoma or advanced non-small-cell lung cancer (NSCLC).
Detailed description
This study is the first-in-human study of IOV-4001, a genetically modified autologous tumor- infiltrating lymphocytes (TIL) product. IOV-4001 is expected to have antitumor activity through its capacity to directly target and kill tumor cells in a manner that is similar to non-genome-edited TIL, but with the potential for enhanced antitumor activity due to disruption of PDCD1, the gene for programmed cell death protein-1 (PD-1).
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Cohort 1 | Experimental | Biological: IOV-4001Participants with unresectable or metastatic melanoma |
| Cohort 2 | Experimental | Biological: IOV-4001Participants with Stage III or IV non-small-cell lung cancer |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- Participants must have a confirmed diagnosis of Stage IIIC, IIID, or IV unresectable or metastatic melanoma or Stage III or IV NSCLC.
- Participants who have received the following previous therapy:
- Participants who have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
- Participants who is assessed as having at least one resectable lesion.
- Participants who have at least one measurable lesion, following resection of the lesion for IOV-4001 generation.
Key exclusion criteria (7 listed)
- Participants who have melanoma of uveal/ocular origin.
- Participants who have symptomatic untreated brain metastases.
- Participants who have had a history of allogeneic organ transplant or any form of cell therapy involving prior conditioning chemotherapy within the past 20 years.
- Participants who require systemic steroid therapy 10 mg/day prednisone or another steroid equivalent dose.
- Participants who have any form of primary immunodeficiency.
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 |
|---|---|---|
| IOV-4001A tumor sample is resected from each participant and cultured ex-vivo to manufacture IOV-4001. After lymphodepleting chemotherapy including cyclophosphamide and fludarabine, participant is infused with IOV-4001, and followed by IL-2. | Biological | Cohort 1, Cohort 2 |
Primary outcome
Phase I: Safety of IOV-4001
Time frame: Up to 1 Year or depending on when the recommended phase 2 dose is determined
The safety of IOV-4001 will be assessed based on the totality of dose-limiting toxicity (DLT) and adverse event (AE) data collected during this phase
Phase 2: Objective Response Rate (ORR)
Time frame: Up to 60 months
To evaluate the proportion of participants who have a confirmed complete response (CR) or partial response (PR) per RECIST v1.1 as assessed by the investigator
7 secondary outcomes
CR Rate
Time frame: Up to 60 months
Duration of Response (DOR)
Time frame: Up to 60 months
Disease Control Rate (DCR)
Time frame: Up to 60 months
Progression-free Survival (PFS)
Time frame: Up to 60 months
Overall Survival (OS)
Time frame: Up to 60 months
Safety and Tolerability of IOV-4001
Time frame: Up to 60 months
Feasibility of IOV-4001
Time frame: Up to 60 months
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 11 Jun 2026.
Related trials for Unresectable Melanoma
RecruitingPhase 3
A Study With Combinations of Anti-LAG-3 and Anti-PD-1 Antibodies in Adult Participants With Advanced or Metastatic Melanoma (Harmony Head-to-Head)
Melanoma
Active, not recruitingPhase 1/2
A Study of ST-1898 for Unresectable or Metastatic Melanoma
Unresectable or Metastatic Melanoma
RecruitingPhase 2
BiCaZO: A Study Combining Two Immunotherapies (Cabozantinib and Nivolumab) to Treat Patients With Advanced Melanoma or Squamous Cell Head and Neck Cancer, an immunoMATCH Pilot Study
Clinical Stage III Cutaneous Melanoma AJCC v8, Clinical Stage III HPV-Mediated (p16-Positive) Oropharyngeal Carcinoma AJCC v8
Active, not recruitingPhase 2
A Study to Evaluate the Efficacy and Safety of IBI363 Monotherapy Compared to Pembrolizumab in Patients With Unresectable Locally Advanced or Metastatic Mucosal or Acral Melanoma Who Had Not Previously Received Systemic Therapy
Melanoma
Active, not recruitingPhase 1/2
A Beta-only IL-2 ImmunoTherapY Study
Advanced Solid Tumor, Unresectable Solid Tumor
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.
Iovance Biotherapeutics Study Team study director
Iovance Biotherapeutics
11 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing IOV-4001 in people with Unresectable Melanoma and Metastatic Melanoma, run by Iovance Biotherapeutics, Inc. at 11 sites 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 16 inclusion and 7 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: looking for participants now, as of the sponsor's last update on 11 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 11 sites 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 combined 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.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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?
Contact Iovance Biotherapeutics Study Team (1-844-845-4682, Clinical.Inquiries@iovance.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Phase I: Safety of IOV-4001 (time frame: Up to 1 Year or depending on when the recommended phase 2 dose is determined). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 11 Jun 2026.