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Non Small Cell Lung CancerPhase 1NCT06034860

Study of MT-8421 as Monotherapy and in Combination With Nivolumab in Patients With Selected Advanced Solid Cancer Types

A Phase 1 study testing MT-8421 and Nivolumab in people with Non Small Cell Lung Cancer and Hepatocellular Carcinoma, run by Molecular Templates, Inc. at 5 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

This is a Phase 1, open-label, dose escalation and expansion study of MT-8421 (an Engineered Toxin Body (ETB)) as monotherapy and in combination with nivolumab in patients with selected advanced solid cancer types. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
MT-8421 and Nivolumab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
15 participants
Where
5 sitesUnited States
Study dates
1 Nov 2023to 31 Oct 2024
Phase
Phase 1
Are there results?
None posted in the registry

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

  • Histologically confirmed, unresectable, locally advanced, or metastatic melanoma, HCC, NSCLC, RCC, MSI-H/dMMR malignancies, urothelial carcinoma, esophageal squamous cell carcinoma, mesothelioma, SCCHN, or cervical carcinoma not amenable to standard treatment, or standard treatment is not available, or in the Investigator's opinion, the standard treatment would not be in the patient's best interest.
  • Part A only: Evaluable only or measurable disease according to RECIST v1.1 Part B only: At least 1 measurable tumor lesion according to RECIST v1.1
  • Prior treatment must include a PD-1 or programmed cell death - ligand 1 (PD-L1) inhibitor. Prior treatment with a CTLA-4 inhibitor is not required.
  • Eastern Cooperate Oncology Group (ECOG) performance score of 0 or 1
  • Adequate bone marrow function, as determined by:
  • Absolute neutrophil count (ANC) ≥ 1500/ μL (should not have received growth factors within 2 weeks prior to screening)
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  • Platelet count ≥ 75,000/ μL
  • Hemoglobin ≥ 8.0 g/dL (no red blood cell transfusion within 2 weeks of study treatment start is allowed)
  • Adequate renal function, based on estimated creatinine clearance (eCrCl) ≥ 50 mL/min, calculated by the Cockcroft-Gault equation.
  • Adequate hepatic function, as determined by:
  • Total bilirubin ≤ 1.5x upper limit of normal (ULN) or ≤ 2x ULN direct bilirubin for patients with Gilbert's Syndrome
  • Aspartate transaminase (AST) ≤ 3x ULN (or ≤ 5x ULN if liver metastasis or HCC).
  • Alanine transaminase (ALT) ≤ 3x ULN (or ≤ 5x ULN if liver metastasis or HCC).
  • Adequate serum albumin (albumin ≥ 2.5 g/dL)
  • Availability of a lesion that can be biopsied with acceptable risk.
  • Patients capable of bearing children must have a negative highly sensitive pregnancy test within 72 hours before the start of treatment. Patients who are postmenopausal (> 1 year since last menstrual cycle) or permanently sterilized (e.g., bilateral tubal occlusion, hysterectomy, bilateral salpingectomy) may be considered as not of reproductive potential.
  • Patients of reproductive potential must agree either to abstain continuously from heterosexual intercourse or to use a highly effective birth control method from signing the informed consent form (ICF) until 30 days after the last dose of MT-8421 and/or 5 months after the last dose of nivolumab for patients capable of bearing children and until 90 days after the last dose of MT-8421 for patients capable of fathering a child. Patients must not donate sperm during the study and for 90 days after the last dose of nivolumab or MT-8421.

Who cannot join

  • Unwilling or unable to undergo 2 sets of 3 to 6 core tumor biopsies: one set at study baseline (prior to first dose of study drug) and one set between Weeks 6 through 8. A final optional set will be collected time of disease progression.
  • Received approved or investigational treatment for the disease under study (except ipilimumab) where Exclusion Criterion 4 applies, requiring a washout that will be dependent upon prior ipilimumab dose and planned MT-8421 dose) within 4 weeks before the start of treatment. For small molecules [Molecular Weight (MW) < 0.9 kDa], the washout is 5 half-lives, but at least 2 weeks.
  • Received tremelimumab within 30 days or ipilimumab 3 mg/kg within 60 days or ipilimumab 1 mg/kg within 30 days before the start of treatment. Once dose cohort of 32 µg/kg MT-8421 has been completed in dose escalation, a 30-day washout of ipilimumab is acceptable irrespective of prior dose.
  • Any concurrent cancer treatment, apart from local treatment of non-target lesions for palliative intent (e.g., local surgery or radiotherapy). Patient must have recovered from the effects of the local treatment and be discussed with the medical monitor.
  • History or current evidence of another neoplastic disease, except cervical carcinoma in situ; superficial non-invasive bladder tumors, curatively treated; Stage I to II non-melanoma skin cancer; prostate cancer managed by active surveillance; or any previous cancer curatively treated < 2 years before the start of treatment.
  • Active autoimmune disease that required systemic treatment in the past. Patients who have not required systemic treatment for at least 2 years may be enrolled if permission is provided after discussion with the Medical Monitor (replacement therapy, e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency is allowed)
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  • Evidence of active, non-infectious ≥ Grade 2 pneumonitis or current evidence of ≥ Grade 3 other underlying pulmonary disease.
  • Ongoing > Grade 1 immune-related toxicity caused by prior CPI therapy (i.e., PD-1 inhibitors, PDL1 inhibitors, or CTLA-4 inhibitors). Patients with stable endocrinological AEs (e.g., hypothyroidism, adrenal insufficiency, hypopituitarism, or diabetes mellitus) must have been on a stable dose of supplemental therapy for at least 2 weeks before screening to be eligible for this study. History of repeat Grade 2 pneumonitis or myocarditis on previous CPI and/or Grade 3 irAE on previous CPI treatment.
  • Current evidence of new or growing central nervous system (CNS) metastases during screening. Patients with known CNS metastases will be eligible if they meet all the following criteria:
  • Received radiotherapy or another appropriate therapy for the CNS metastases, if clinically Indicated
  • Have stable CNS disease on the computed tomography (CT) or magnetic resonance imaging (MRI) scan within 4 weeks before signing the ICF compared with prior neuroimaging.
  • History or current evidence of significant cardiovascular disease before the start of treatment.
  • Current evidence of active, uncontrolled hepatitis B virus, hepatitis C virus, human immunodeficiency virus (HIV) (evidenced by detectable viral load by polymerase chain reaction) or acquired immunodeficiency syndrome (AIDS)-related illness.
  • Serology and virology measurements are not required to be performed at screening, but any previously reported results should be used for eligibility purposes. Investigators will test per their discretion
  • Patients with a history of treated hepatitis C and non-quantifiable hepatitis C virus- ribonucleic acid (RNA) may be enrolled.
  • Patients on treatment for hepatitis B, hepatitis C, and/or HIV will be eligible if they have undetectable viral load (patients with HIV with CD4+ T-cell [CD4+] counts ≥ 350 cells/µL may be enrolled).
  • Patients with unintentional weight loss greater than 10% of their body weight over the preceding 2 months or less prior to first dose in the first cycle.

Trial locations and contacts

5 sites in 1 country.

5 sites in 1 country

United States5 sites

  • NEXT Oncology

    Fairfax, Virginia, 22031

  • Horizon Oncology Research, LLC

    Lafayette, Indiana, 47905

  • The Angeles Clinic

    Los Angeles, California, 90025

  • Weill Cornell Medicine

    New York, New York, 10065

  • Washington University in St. Louis

    St Louis, Missouri, 63110

Other trials in United States

About this study

Official title: A Phase 1 Open-label, Multicenter, Dose-ranging Study to Investigate Safety and Tolerability, Efficacy, Pharmacokinetics, Pharmacodynamics, and Immunogenicity of MT-8421 as Monotherapy and in Combination With Nivolumab in Patients With Selected Advanced Solid Cancer Types

This is a Phase 1, open-label, dose escalation and expansion study of MT-8421 (an Engineered Toxin Body (ETB)) as monotherapy and in combination with nivolumab in patients with selected advanced solid cancer types. MT-8421 is an investigational drug that specifically targets and depletes cytotoxic T-lymphocytes-associated protein 4 (CTLA-4) expressing cells in an effort to directly dismantle the tumor microenvironment for the treatment of patients with advanced solid tumors.

Read the detailed description

This study is conducted in two parts. The study will enroll up to 200 total participants (up to 40 in Part A and up to 160 in Part B).

Part A (Dose Escalation) is designed to estimate the maximum tolerated dose (MTD) of MT-8421 as monotherapy and in combination with nivolumab.

Part B (Dose Expansion) is designed to identify the dose(s) to be studied in Phase 2.

The drug being tested in this study is called MT-8421. The study will evaluate safety, tolerability, efficacy, pharmacokinetics, pharmacodynamics, and immunogenicity of MT-8421 as monotherapy and in combination with nivolumab in patients with selected advanced solid cancer types.

MT-8421 will be given as an intravenous (IV) infusion on Days 1, 8, 15, and 22 of a 28-day cycle. H1 and H2 blockers and anti-pyretics will be given to all patients as pre-medication prior to each dose in Cycle 1. Anti-pyretics will be required for 24 hours after the first dose in Cycle 1. Use of pre-medication will be at the discretion of the Investigator for subsequent doses.

In Parts A and B, a subject may participate for the following three (3) periods:

  • Screening Period- up to 28 days before the first dose of MT-8421
  • Treatment Period- active period where a subject will receive doses of MT-8421 over a 28-day treatment period.
  • Follow-up Period- up to 24 months after the second short term follow up visit.

In both parts of the study, participants can receive MT-8421 until their cancer worsens, side effects prevent further study treatment, or until the participant leaves the study for other reasons decided by the participant, the study doctor, or the sponsor of the study. After the second short term follow up visit participants will have a check -up of their disease every 12 weeks for 24 months.

The overall duration of the study will vary for each participant because study treatment will continue until unacceptable toxicity, withdrawal of consent, death, termination of the study by the sponsor, or fulfilment of another discontinuation criterion.

Being tested
MT-8421, Nivolumab
Medical subject headings
Carcinoma, Non-Small-Cell Lung, Carcinoma, Hepatocellular, Melanoma, Carcinoma, Renal Cell, Turcot syndrome, Mesothelioma, Esophageal Squamous Cell Carcinoma, Squamous Cell Carcinoma of Head and Neck

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • MT-8421Drug

    Experimental treatment with MT-8421

  • NivolumabDrug

    480 mg nivolumab administered on Day 1 of each cycle starting with Cycle 2 for all combination dose escalation and dose expansion cohorts

Study groups in NCT06034860
Study groupRoleWhat they receive
Part A- Dose Escalation MonotherapyExperimentalPart A- Dose escalation of MT-8421 monotherapy in patients with selected advanced solid tumors. The assigned dose level of MT-8421 will be given as an intravenous (IV) infusion over about 30 minutes on the same day every week (i.e. on day 1, day 8, day 15, and day 22 of each 28-day cycle).
Receives: Drug: MT-8421
Part A- Dose Escalation Combination TherapyExperimentalPart A- Dose escalation of MT-8421 in combination with nivolumab in patients with selected advanced solid tumors. The assigned dose level of MT-8421 will be given as an intravenous (IV) infusion over about 30 minutes prior to the infusion of 480 mg nivolumab. MT-8421 will be given on the same day every week (i.e. on day 1, day 8, day 15, and day 22 of each 28-day cycle). Nivolumab will be given on the first day of each cycle beginning at cycle 2.
Receives: Drug: MT-8421; Drug: Nivolumab
Part B Dose Expansion MonotherapyExperimentalPart B- Dose expansion of MT-8421 monotherapy in patients with selected advanced solid tumors. Part B monotherapy will include two expansion groups: Group B1 (NSCLC) and group B2 (HCC). The assigned dose level of MT-8421 determined in Part A will be given as an intravenous (IV) infusion over about 30 minutes on the same day every week (i.e. on day 1, day 8, day 15, and day 22 of each 28-day cycle).
Receives: Drug: MT-8421
Part B Dose Expansion CombinationExperimentalPart B- Dose escalation of MT-8421 in combination with nivolumab in patients with selected advanced solid tumors. Part B combination therapy will include two expansion groups: Group B3 (Melanoma) and Group B4 (RCC). The assigned dose level of MT-8421 determined in Part A will be given as an intravenous (IV) infusion over about 30 minutes prior to the infusion of 480 mg nivolumab. MT-8421 will be given on the same day every week (i.e. on day 1, day 8, day 15, and day 22 of each 28-day cycle). Nivolumab will be given on the first day of each cycle beginning at cycle 2.
Receives: Drug: MT-8421; Drug: Nivolumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of participants with Adverse Events

    Evaluation of safety and tolerability of MT-8421 as measured by number of participants with Adverse Events, dose limiting toxicities (DLTs), abnormal physical exam findings, abnormal laboratory test results, abnormal radiographic findings, and/or patient reported symptoms

    Measured: 28 day cycle

  2. To confirm the recommended Phase 2 dose (RP2D) of MT-8421 as monotherapy and in combination with nivolumab in patients with selected advanced solid tumor types.

    Incidence of AEs

    Measured: 28 day cycle

  3. Proportion of participants with objective response

    Objective response rate (ORR) defined as the proportion of participants with either a complete response or a partial response as determined by investigator assessment using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)

    Measured: Up to two years (Part B)

Secondary outcomes (11)

  1. Objective response rate to assess preliminary efficacy

    Objective response rate (ORR) defined as the proportion of participants with either a complete response or a partial response as determined by investigator assessment using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)

    Measured: Up to two years (Parts A)

  2. Duration of response to assess preliminary efficacy

    Duration of response defined for participants with confirmed complete response or partial response as the time from the first documented tumor response to the date of radiographic progression progressive disease per RECIST v1.1

    Measured: Up to two years (Parts A)

  3. Time to response to assess preliminary efficacy

    Time to response defined as the time from the date of the first dose of the study treatment to the date of the first documentation of response (partial response or better) per RECIST v1.1

    Measured: Up to two years (Parts A)

  4. Progression-free survival to assess preliminary efficacy

    Progression free survival defined as the time from the start of treatment with MT-8421 to the date of radiographic progressive disease per RECIST v1.1 or death from any cause, not including clinical progression

    Measured: Up to two years (Parts A)

  5. Disease control rate to assess preliminary efficacy

    Disease control rate defined as proportion of patients who have achieved complete response, partial response and stable disease

    Measured: Up to two years (Parts A)

  6. Characterize the pharmacokinetic (PK) profile of MT-8421 given as monotherapy and in combination with nivolumab in patients with selected advanced solid tumor types

    Maximum observed plasma concentration (Cmax)

    Measured: Up to two years (Parts A)

  7. Characterize the pharmacokinetic (PK) profile of MT-8421 given as monotherapy and in combination with nivolumab in patients with selected advanced solid tumor types

    Half-life (t1/2)

    Measured: Up to two years (Parts A and B)

  8. Characterize the pharmacokinetic (PK) profile of MT-8421 given as monotherapy and in combination with nivolumab in patients with selected advanced solid tumor types

    Area under the concentration-time curve (AUC) from time zero to the last measurable concentration (AUC0-t), total exposure (AUC0-∞)

    Measured: Up to two years (Parts A and B)

  9. Characterize the pharmacokinetic (PK) profile of MT-8421 given as monotherapy and in combination with nivolumab in patients with selected advanced solid tumor types

    Clearance (CL)

    Measured: Up to two years (Parts A and B)

  10. Characterize the pharmacokinetic (PK) profile of MT-8421 given as monotherapy and in combination with nivolumab in patients with selected advanced solid tumor types

    Volume of distribution at steady-state (Vss)

    Measured: Up to two years (Parts A and B)

  11. Evaluate the immunogenicity of MT-8421 in patients with selected advanced solid tumors.

    Anti-drug antibodies (ADA), Neutralizing antibodies (NAb)

    Measured: Up to two years (Parts A and B)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted13 Sep 2023
  2. Study start1 Nov 2023
  3. Primary completion31 Oct 2024
  4. Study completion31 Oct 2024

Why it stopped: Sponsor Termination

Resources

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
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
15 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06034860
Sponsor's protocol ID
MT-8421-001
Status last verified
Oct 2024
First submitted
23 Aug 2023
Last updated
1 Nov 2024
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing MT-8421 and Nivolumab in people with Non Small Cell Lung Cancer and Hepatocellular Carcinoma, run by Molecular Templates, Inc. at 5 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 17 inclusion and 17 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: stopped early, as of the sponsor's last update on 1 Nov 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 5 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 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?

The study was stopped early (reason given: Sponsor Termination). Results are not available in the source record.

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?

Number of participants with Adverse Events (time frame: 28 day cycle). The study lists 3 primary outcomes in all. 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 NCT06034860.

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 1 Nov 2024.

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