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Non-small Cell Lung Cancer (NSCLC)Phase 1NCT02840994

A Trial of CV301 in Combination With Anti-PD-1 Therapy in Subjects With Non-Small Cell Lung Cancer

A Phase 1 study testing CV301, Pembrolizumab and Nivolumab in people with Non-small Cell Lung Cancer (NSCLC), run by Bavarian Nordic at 7 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

The objective of the proposed clinical trial is to investigate the safety and tolerability of CV301 in combination with Anti-PD1-Therapy in subjects with non-small cell lung cancer (NSCLC). The clinical trial is designed to evaluate the possible enhanced antitumor activity of CV301 with Anti-PD1-Therapy. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Non-small Cell Lung Cancer (NSCLC)
What is being tested?
CV301, Pembrolizumab and Nivolumab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
24 participants
Where
7 sitesUnited States
Study dates
Dec 2016to Jan 2020
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

  • Subjects must have a metastatic or unresectable locally advanced malignant solid tumor, histologically confirmed by the Laboratory of Pathology, NCI. Efforts will be made, as much as possible, to enroll subjects with tumor types with known increased expression of CEA or MUC-1 (such as lung, breast, ovarian, prostate, colorectal, pancreatic, bladder, gastric, cervix, etc.).
  • Subjects may have measurable or nonmeasurable but evaluable disease. Subjects with surgically resected or ablated metastatic disease at high risk of relapse are also eligible.
  • Prior therapy: Subjects must have completed or had disease progression on at least one prior line of disease-appropriate therapy for locally advanced or metastatic disease, or not be candidates for therapy of proven efficacy for their disease.
  • Subjects with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations.
  • There should be a minimum of 4 weeks from any prior chemotherapy, immunotherapy and/or radiation, with the exception of hormonal therapy for prostate and breast cancers, HER2-directed therapy for HER2+ breast cancer (3+ IHC or FISH+), maintenance therapy for colorectal or pancreatic cancer, and erlotinib therapy in EGFR-mutated lung cancer under the condition that subjects are on these therapies for at least two months before start of trial treatment. There should be a minimum of 6 weeks from any prior antibody therapies (such as ipilimumab or Anti-PD1/PDL1) due to prolonged half-life.
  • Subjects must have recovered (Grade 1 or baseline) from any clinically significant toxicity associated with prior therapy. Typically, this is 3-4 weeks for subjects who most recently received cytotoxic therapy, except for nitrosoureas and mitomycin C, for which 6 weeks is needed for recovery.
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  • Men or women, age ≥ 18 years.
  • Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1 or Karnofsky ≥ 70%, (see Section 19.1, Appendix I and Section 19.2, Appendix II).
  • Subjects must have normal organ and marrow function as defined below
  • Serum creatinine ≤ 1.5 x upper limit of normal (ULN) OR creatinine clearance (CrCl) ≥ 40 mL/min (if using the Cockcroft-Gault formula below): i. Female CrCl = [(140 - age in years) x weight in kg x 0.85] / [72 x serum creatinine in mg/dL] ii. Male CrCl = [(140 - age in years) x weight in kg x 1.00] / [72 x serum creatinine in mg/dL] b. Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) ≤ 3 x the ULN c. Total bilirubin ≤ 1.5 x ULN OR in subjects with Gilbert's syndrome, a total bilirubin ≤ 3.0 x ULN d. Hematological eligibility parameters (within 16 days of starting therapy): i. Platelet count ≥ 100,000/µL ii. Absolute neutrophil count (ANC) ≥ 1/ µL
  • Subjects must have baseline pulse oximetry > 90% on room air.
  • The effects of CV301 on the developing human fetus are unknown. For this reason, women of child-bearing potential (WOCBP) and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to trial entry and for the duration of trial participation and for a period of 4 months after the last vaccination. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this trial, she should inform her treating physician immediately.
  • Subjects with prostate cancer must continue to receive GnRH agonist therapy (unless orchiectomy has been done).
  • Subjects must be able to understand and be willing to sign a written informed consent document.
  • Histologically confirmed non-squamous NSCLC, metastatic or unresectable locally advanced. Actionable EGFR mutations and ALK/ROS-1 translocations targetable with FDA approved therapy must be evaluated and found not to be present by standard methods. Expression of PD-L1 must have been determined with a validated method or tumor sample must be available for PD-L1 expression determination.
  • Patient population:
  • Phase 1b, Cohort 1 (Nivolumab + CV301): Patients with progression on or after prior platinum, with or without switch maintenance chemotherapy are eligible
  • Phase 1b, Cohort 2 (Pembrolizumab + CV301): Patients must have been on Pembrolizumab as first-line therapy for NSCLC as per FDA approved indications in first line for at least 11 weeks and assessed by RECIST to have CR, PR, or SD at week 12 (+/- 1 week).
  • As of June 2017, FDA-approved indications for front-line treatment include 2 indications for Pembrolizumab:
  • As a single agent for the first-line treatment of patients with metastatic NSCLC whose tumors have high PD-L1 expression (Tumor Proportion Score (TPS) ≥50%) as determined by an FDA-approved test, with no EGFR or ALK genomic tumor aberrations.
  • In combination with pemetrexed and carboplatin, as first-line treatment of patients with metastatic nonsquamous NSCLC. This indication is approved under accelerated approval based on tumor response rate and progression-free survival. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.
  • Pemetrexed single agent maintenance after the initial 4 cycles of pemetrexed in combination with carboplatinum and Pembrolizumab is allowed and optional as per investigator or institutional standard practice.
  • In case of metastatic recurrence of a previous early stage NSCLC, any chemotherapy or radiation therapy must have finalized more than 12 months before the start of the first-line treatment, either Pembrolizumab alone or in combination with pemetrexed and carboplatinum.
  • ECOG performance status 0 and 1.
  • Men or women, age ≥ 18 years
  • Have normal organ and marrow function as defined below:
  • Serum creatinine ≤ 1.5 x upper limit of normal (ULN) OR creatinine clearance (CrCl) ≥ 40 mL/min (if using the Cockcroft-Gault formula below):
  • Female CrCl = [(140 - age in years) x weight in kg x 0.85] / [72 x serum creatinine in mg/dL] ii. Male CrCl = [(140 - age in years) x weight in kg x 1.00] / [72 x serum creatinine in mg/dL]
  • ANC > 1/µL
  • Platelets ≥ 100 000/µL
  • Hemoglobin > 9 g/dL
  • Total bilirubin ≤ 1.5 x institutional ULN or direct bilirubin < ULN if total bilirubin > 1.5-3.0 x ULN
  • AST/ALT < 2.5 × institutional ULN, or < 5 x ULN, if liver metastases are present
  • Have measurable disease by computed tomography (CT)/Magnetic resonance imaging (MRI) per RECIST 1.1.
  • Willingness and ability to comply with scheduled visits, treatment plan, laboratory tests, and other trial procedures.
  • Able to understand and be willing to sign a written informed consent document.
  • WOCBP must use appropriate method(s) of contraception. WOCBP should use an adequate method to avoid pregnancy for 23 weeks (30 days plus the time required for Nivolumab to undergo five half-lives) after the last dose of investigational drug (Phase 1b, Cohort 1). WOCBP should use an adequate method to avoid pregnancy for at least 4 months (as per approved Pembrolizumab prescribing information) after the last dose of investigational drug (Phase 1b, Cohort 2).
  • Women of childbearing potential must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of β-human choriogonadotropin (HCG)) at screening. They must have confirmation by a negative urine pregnancy test within 24 hours prior to the first dose of Nivolumab (Phase 1b, Cohort 1), or within 24 hours prior to the first dose of Pembrolizumab (Phase 1b, Cohort 2) in the setting of this trial.
  • Men who are sexually active with WOCBP must use any contraceptive method with a failure rate of less than 1% per year. Men receiving Nivolumab and who are sexually active with WOCBP will be instructed to adhere to contraception for a period of 31 weeks after the last dose of investigational product. Women who are not of childbearing potential (ie, who are postmenopausal or surgically sterile) as well as azoospermic men, do not require contraception.
  • Subjects must have, prior to trial treatment, at least 10 unstained tissue slides (or a tissue block from which 10 slides can be cut) from a prior biopsy or surgical resection for submission for research purposes.
  • Optional for Phase 1b.

Who cannot join

  • Subjects with EGFR mutations, ALK or ROS-1 translocations candidates to targeted therapy.
  • Squamous histology of NSCLC.
  • Other concurrent investigational agents (subjects are eligible to enroll 4 weeks after completion of prior investigational agent).
  • More than 1 prior chemotherapy regimen for locally advanced or metastatic NSCLC with the exception of the Phase 1 portion, in which multiple therapies are allowed in all tumor types. Any prior chemotherapy regimen different from pemetrexed-carboplatinum in combination with Pembrolizumab as first-line chemotherapy for candidates to Pembrolizumab maintenance of first line (Phase 1b).
  • Concurrent chemotherapy or radiotherapy or other immunotherapy not explicitly allowed by inclusion criteria for that phase of trial.
  • Subjects treated with PD-1/L1 or any other experimental immunotherapeutic agents outside the parameters established in the inclusion criteria, are excluded from enrollment into Phase 1b, but can be enrolled into Phase 1.
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  • Other malignancy within last 5 years with an estimated risk of recurrence higher than 50%. Examples of low risk of recurrence malignancies are non-melanoma skin cancer, in situ cervical, superficial bladder cancer, colorectal cancer stage I and II, breast cancer stages I and II, prostate cancer stages I and II, etc.
  • Patients with metastatic lesions in the brain.
  • History of allergy or untoward reaction to prior vaccination with vaccinia virus, aminoglycoside antibiotics or egg products; history of allergy to smallpox vaccination.
  • Active infection within 72 hours prior to vaccination.
  • Subjects should have no known evidence of being immunocompromised as listed below:
  • Human immunodeficiency virus (HIV) positivity, chronic hepatitis infection, including hepatitis B and C virus
  • Active, known or suspected autoimmune disease. Subjects are permitted to enroll if they have vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger
  • Immunosuppressive therapy post-organ transplant
  • Asplenia is an exclusion for Phase 1b, but is not an exclusion for Phase 1.
  • Altered immune function, including, but not limited to: inflammatory bowel disease; active infectious enteritis; eosinophilic enteritis; lupus erythematosus; ankylosing spondylitis; scleroderma; multiple sclerosis. These criteria do not include all diseases with an immune-related component, but are not auto-immune in nature or have a primary alteration in the general immune function that may interfere with the vaccine mechanism of action, for example celiac disease.
  • Concurrent chronic use of systemic steroids, except for physiologic doses of systemic steroids for replacement, defined as 5 mg of prednisone per day or equivalent, or local (topical, nasal, ophthalmic or inhaled) steroid use or prior concomitant use with chemotherapy. Systemic steroids must have been discontinued ≥ 2 weeks prior to first treatment. Prior use of corticoids in short-term schemes (duration shorter than 3 days) for indications such as prophylaxis of reactions to intravenous contrast for imaging studies or chemotherapy-related AEs are not considered part of this exclusion. Prior use of corticoids for brain metastasis ending before day -14 is not considered part of this exclusion criteria.
  • Subjects with interstitial lung disease that is symptomatic or may interfere with the detection or management of suspected drug-related pulmonary toxicity.
  • Pregnant or breastfeeding women.
  • Clinically significant cardiomyopathy, coronary disease, heart failure New York Heart Association class III or IV, or cerebrovascular accident within 1 year.
  • Uncontrolled intercurrent illness, which would interfere with the ability of the subject to carry out the treatment program.
  • Any other condition, which would, in the opinion of the Principal Investigator or Medical Monitor, indicate the subject is a poor candidate for treatment with CV301 or would jeopardize the subject or the integrity of the data obtained.
  • Medical or psychological impediment to compliance with protocol.

Trial locations and contacts

7 sites in 1 country.

7 sites in 1 country

United States7 sites

  • NCI

    Bethesda, Maryland, 20892

  • Millennium Oncology

    Houston, Texas, 77090

  • Investigative Clinical Research of Indiana

    Indianapolis, Indiana, 46260

  • Metairie Oncologist, LLC

    Metairie, Louisiana, 70006

  • Washington University School of Medicine

    St Louis, Missouri, 63110

  • H. Lee Moffitt Cancer Center & Research Institute, Inc.

    Tampa, Florida, 33612

  • Novant Health Oncology Specialists

    Winston-Salem, North Carolina, 27103

Other trials in United States

About this study

Official title: A Phase 1 Trial of CV301 in Combination With Anti- PD-1 Therapy in Subjects With Non-Small Cell Lung Cancer

The objective of the proposed clinical trial is to investigate the safety and tolerability of CV301 in combination with Anti-PD1-Therapy in subjects with non-small cell lung cancer (NSCLC).

The clinical trial is designed to evaluate the possible enhanced antitumor activity of CV301 with Anti-PD1-Therapy. The rationale for combining CV301 with Anti-PD1-Therapy is based on the hypothesis that CV301 can induce specific immune response in the tumor, and that in combination, Anti-PD1-Therapy may augment the T cell-mediated immune response generated by CV301 by blocking the inhibitory signal of the PD-1.

Read more

The trial will include a Phase 1 portion and a Phase 1b portion with 2 cohorts. The Phase 1 portion is a dose escalation part to assess the safety and tolerability of CV301 alone, prior to moving into the combination with Anti-PD1-Therapy (the Phase 1b component).

The following Phase 1b portion of the trial aims to test the safety and tolerability of the combination treatment using a two cohort approach with cohort 1 receiving CV301 plus Nivolumab and cohort 2 receiving CV301 plus Pembrolizumab.

Being tested
CV301, Pembrolizumab, Nivolumab
Keywords
CV301, NSCLC, Pembrolizumab, Nivolumab
Medical subject headings
Carcinoma, Non-Small-Cell Lung

What participants receive

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

Study groups in NCT02840994
Study groupRoleWhat they receive
CV301 + PembrolizumabExperimentalCV301 + Pembrolizumab (Phase 1b portion of the trial)
Receives: Biological: CV301; Biological: Pembrolizumab
CV301 + NivolumabExperimentalCV301 + Nivolumab (Phase 1b portion of the trial)
Receives: Biological: CV301; Biological: Nivolumab

What is being measured

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

  1. Safety and tolerability of CV301 alone and in combination determined by incidence of dose-limiting toxicities (DLTs)

    Safety and tolerability following administration of CV301 alone (Phase 1) and in combination with Nivolumab or Pembrolizumab (Phase 1b), respectively, as determined by the incidence of dose-limiting toxicities (DLTs).

    Measured: Through study completion, up to 2 years

Timeline

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

  1. First posted21 Jul 2016 (estimated)
  2. Study startDec 2016
  3. Primary completionJan 2020
  4. Study completionJan 2020

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
24 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02840994
Sponsor's protocol ID
CV301-2015-201
Other IDs
MAGNI-LUNG-01
Status last verified
Feb 2020
First submitted
18 Jul 2016
Last updated
27 Feb 2020
Results posted
No
Data monitoring committee
No
Individual data sharing
Undecided: Undecided

Publications

  • Rajan A, Gray JE, Devarakonda S, Birhiray R, Korchin B, Menius E, Donahue RN, Schlom J, Gulley JL. Phase 1 trial of CV301 in combination with anti-PD-1 therapy in nonsquamous non-small cell lung cancer. Int J Cancer. 2023 Feb 1;152(3):447-457. doi: 10.1002/ijc.34267. Epub 2022 Sep 9.

    PubMed 36054490

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing CV301, Pembrolizumab and Nivolumab in people with Non-small Cell Lung Cancer (NSCLC), run by Bavarian Nordic at 7 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 41 inclusion and 23 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: finished, as of the sponsor's last update on 27 Feb 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 7 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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

Safety and tolerability of CV301 alone and in combination determined by incidence of dose-limiting toxicities (DLTs) (time frame: Through study completion, up to 2 years). 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 NCT02840994, 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 27 Feb 2020.

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