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Non-Small Cell Lung Cancer (NSCLC)Phase 2IGNYTENCT03767348

Study of RP1 Monotherapy and RP1 in Combination With Nivolumab (IGNYTE)

A Phase 2 study testing RP1 and nivolumab in people with Non-Small Cell Lung Cancer (NSCLC) and Microsatellite Instability-High (MSI-H), run by Replimune, Inc. at 51 sites in 5 countries.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
Search all trials

Trial summary

The Phase 2 study is a multicenter, open-label study of RP1 to further investigate safety and to estimate the efficacy of RP1 at the RP2D in combination with nivolumab in patients with Stage IIIb-IV unresectable melanoma, microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) solid tumors… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
RP1 and nivolumab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
340 participants
Where
51 sitesin 5 countries
Study dates
20 Sep 2017to Dec 2028
Phase
Phase 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 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Have an Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1.
  • At least one measurable and injectable lesion
  • Have provided a former tumor pathology specimen or be willing to supply a new tumor sample from a biopsy
  • Have a predicted life expectancy of ≥ 3 months
  • Measurable disease, according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria
  • Subjects with MSI-H or dMMR tumors: has diagnosis of MSI-H or metatstatic dMMR tumor (according to protocol definition) who has progressed on prior anti-PD1/PD-L1 therapy.
Show all 9Show fewer
  • Subjects with NMSC: has diagnosis of locally advanced or metastatic NMSC that are not considered treatable by surgery including basal cell carcinoma, cutaneous squamous cell carcinoma, basosquamous carcinoma, Merkel cell carcinoma and other non-melanoma skin cancers (per protocol). Patients must have received 8 weeks of anti-PD1/PD-L1 as their last line of therapy and progressed while on treatment.
  • Subjects with anti-PD1 failed cutaneous melanoma: has confirmed progressive disease while on anti-PD1 treatment for at least 8 weeks and documented BRAF mutation status
  • Subjects with anti-PD1 failed NSCLC: must have failed prior treatment, including PD1/PD-L1 directed therapy administered either as monotherapy or in combination with platinum-based chemotherapy or anti-CTLA-4. The most recent treatment given must have included an anti-PD1/PD-L1 directed therapy with radiologic disease progression on or after treatment.

Who cannot join

  • Prior treatment with an oncolytic therapy
  • History of viral infections according to the protocol
  • Prior complications with herpes infections
  • Chronic use of anti-virals
  • Uncontrolled/untreated brain metastasis
  • History of interstitial lung disease
  • History of non-infectious pneumonitis
  • History of clinically significant cardiovascular disease

Trial locations and contacts

51 sites in 5 countries.

51 sites in 5 countries

United States26 sites

  • University of Birmingham Alabama

    Birmingham, Alabama, 35294

  • MUSC Health

    Charleston, South Carolina, 29425

  • University of Cincinnati Medical Center

    Cincinnati, Ohio, 45267

  • Duke Cancer Center

    Durham, North Carolina, 27710

  • West Cancer Center

    Germantown, Tennessee, 38138

  • Banner MD Anderson Cancer Center

    Gilbert, Arizona, 85234

  • The University of Texas MD Anderson Cancer Center

    Houston, Texas, 77030

  • University of Iowa-Cancer Center Research

    Iowa City, Iowa, 52242

  • UC San Diego

    La Jolla, California, 92093

  • Carti Cancer Center

    Little Rock, Arkansas, 72205

  • University of Southern California

    Los Angeles, California, 90033

  • UCLA

    Los Angeles, California, 90095

  • James Graham Brown Cancer Center- University of Louisville

    Louisville, Kentucky, 40202

  • University of Wisconsin-Carbone Cancer Center

    Madison, Wisconsin, 53792

  • Sylvester Comprehensive Cancer Center- University of Miami

    Miami, Florida, 33136

  • Eccles Outpatient Care Center- Oncology Clinical Trials

    Murray, Utah, 84107

  • New York University Clinical Cancer Center

    New York, New York, 10016

  • Weill Cornell Medical College

    New York, New York, 10065

  • University of California, Irvine

    Orange, California, 92868

  • Mayo Clinic

    Phoenix, Arizona, 85054

  • Providence Portland Medical Center

    Portland, Oregon, 97213

  • Mayo Clinic

    Rochester, Minnesota, 55905

  • University of Rochester Medical Center

    Rochester, New York, 14642

  • University of California- San Francisco

    San Francisco, California, 94115

  • Seattle Cancer Care Alliance- University of Washington

    Seattle, Washington, 98109

  • Intermountain Cancer Center- Saint George Cancer Center

    St. George, Utah, 84790

Other trials in United States

France8 sites

  • CHU Besancon - Hopital Jean Minjoz

    Besançon, 25000

  • Institut Bergonié

    Bordeaux, 33076

  • CHU Dijon

    Dijon, 21079

  • Centre Léon Bérard Lyon

    Lyon, 69373

  • Service de Dermatologie et Cancerologie Cutanee Hopital de la Timone

    Marseille, 13005

  • CHU de Nice Hôpital l'Archet

    Nice, 06200

  • Hôpital Saint Louis APHP

    Paris, 75010

  • Institut Gustave Roussy

    Villejuif, 94800

Other trials in France

Spain7 sites

  • Hospital Universitari Vall d'Hebron

    Barcelona, 08035

  • Hospital Clinic Barcelona

    Barcelona, 08036

  • Clínica Universidad de Navarra (Madrid)

    Madrid, 28027

  • Hospital Universitario Virgen de la Arrixaca

    Murcia, 30120

  • Clinica Universitaria de Navarra

    Pamplona, 31008

  • Hospital Universitario Virgen del Rocio

    Seville, 41013

  • Hospital General Universitario de Valencia

    Valencia, 46014

Other trials in Spain

United Kingdom6 sites

  • The Clatterbridge Cancer Centre NHS Foundation Trust

    Bebington, Wirral, CH634JY

  • Beatson West of Scotland Cancer Center

    Glasgow, Scotland, G12 0YN

  • University of Leeds- Teaching Hospital

    Leeds, England, LS97TF

  • Royal Marsden Hospital

    London

  • Oxford University Hospitals NHS Trust

    Oxford, Oxfordshire

  • Southampton General Hospital

    Southampton, SO16 6YD

Other trials in United Kingdom

Germany4 sites

  • Charité (Campus Benjamin Franklin)

    Berlin, 12203

  • University Hospital Essen, Klinik für Dermatologie

    Essen, 45147

  • University of Kiel (UKSH), Dep. of Dermatology

    Kiel, 24105

  • Uniklinik Marburg

    Marburg, 35043

Other trials in Germany

About this study

Official title: An Open-Label, Multicenter, Phase 1/2 Study of RP1 as a Single Agent and in Combination With PD1 Blockade in Patients With Solid Tumors [IGNYTE]

The Phase 2 study is a multicenter, open-label study of RP1 to further investigate safety and to estimate the efficacy of RP1 at the RP2D in combination with nivolumab in patients with Stage IIIb-IV unresectable melanoma, microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) solid tumors, non-melanoma skin cancer (NMSC), and non-small cell lung cancer (NSCLC).

Being tested
RP1, nivolumab
Keywords
RPL-001-16, Stage IIIb-IV Unresectable Melanoma, Non-melanoma Skin Cancer, Mismatch Repair Deficient (dMMR) Solid Tumors
Medical subject headings
Carcinoma, Non-Small-Cell Lung, Melanoma, Turcot syndrome

What participants receive

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

  • RP1Biological

    Genetically modified herpes simplex type 1 virus

  • nivolumabBiological

    Also called Opdivo

    anti-PD-1 monoclonal antibody

Study groups in NCT03767348
Study groupRoleWhat they receive
Dose escalation of RP1 by intratumoral (IT) injection in superficial tumorsExperimentalanti-PD-1 monoclonal antibody
Receives: Biological: RP1
Dose escalation of RP1 by intratumoral (IT) injection in deep/visceral tumorsExperimentalDose escalation of RP1 alone in 3 cohorts with IT injections in superficial tumors
Receives: Biological: RP1
Dose expansion of RP1 and nivolumab (IV) in superficial tumorsExperimentalDose escalation of RP1 alone in 3 cohorts with IT injections in superficial tumors
Receives: Biological: RP1; Biological: nivolumab
Dose expansion of RP1 and nivolumab (IV) in deep/visceral tumorsExperimentalDoses of RP1 (IT) in deep/visceral tumors with nivolumab (IV)
Receives: Biological: RP1; Biological: nivolumab
RP1 (IT) and nivolumab (IV) in melanomaExperimentalDoses of RP1 (IT) in superficial or deep tumors with nivolumab (IV) in subjects with melanoma
Receives: Biological: RP1; Biological: nivolumab
RP1 (IT) and nivolumab (IV) in MSI-H/dMMR solid tumorsExperimentalDoses of RP1 (IT) in superficial or deep tumors with nivolumab (IV) in subjects with MSI-H or dMMR solid tumors
Receives: Biological: RP1; Biological: nivolumab
RP1 (IT) and nivolumab (IV) in NMSCExperimentalDoses of RP1 (IT) in superficial or deep tumors with nivolumab (IV) in subjects with non-melanoma skin cancer
Receives: Biological: RP1; Biological: nivolumab
RP1(IT) and nivolumab (IV) in anti-PD1 Failed Cutaneous MelanomaExperimentalDoses of RP1 (IT) in superficial or deep tumors with nivolumab (IV) in subjects with cutaneous melanoma who have been previously treated with anti-PD1 therapy
Receives: Biological: RP1; Biological: nivolumab
RP1(IT) and nivolumab (IV) in anti-PD1/PD-L1 Failed NMSCExperimentalDoses of RP1 (IT) in superficial or deep tumors with nivolumab (IV) in subjects with non-melanoma skin cancer who have been previously treated with anti-PD1/PD-L1 therapy
Receives: Biological: RP1; Biological: nivolumab
RP1(IT) and nivolumab (IV) in anti-PD1/PD-L1 Failed NSCLCExperimentalDoses of RP1 (IT) in superficial or deep tumors with nivolumab (IV) in subjects with non small cell lung cancer who have been previously treated with anti-PD1/PD-L1 therapy
Receives: Biological: RP1; Biological: nivolumab

What is being measured

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

  1. Percentage of adverse events (AEs)

    Percentage of subjects with adverse events (AEs)

    Measured: 26 months

  2. Percentage of serious adverse events (SAEs)

    Percentage of subjects with serious adverse events (SAEs)

    Measured: 26 months

  3. Percentage of dose limiting toxicities (DLTs)

    Percentage of subjects with dose limiting toxicities (DLTs)

    Measured: 26 months

  4. Percentage of overall response rate (ORR)

    Percentage of overall response rate (ORR) for all participants

    Measured: 26 months

  5. Maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D) of RP1

    Assess the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D) of RP1 based on the safety and response data collected during Phase 1 Escalation

    Measured: 20 weeks

Secondary outcomes (6)

  1. Percentage of biologic activity

    Percentage of subjects with biological activity determined by tumor biopsies and biomarker data

    Measured: 20 weeks

  2. Percentage subjects with detectable RP1

    Data gathered from blood, urine, swabs of injection site, dressings, and oral mucosa to determine the shedding and biodistribution of RP1

    Measured: 20 weeks

  3. Percentage of complete response (CR)

    Percentage of subjects with a complete response (CR)

    Measured: 26 months

  4. Median duration of response

    Median duration of response of subjects

    Measured: 26 months

  5. Median progression-free survival

    Median duration of progression-free survival of subjects

    Measured: 26 months

  6. Median overall survival

    Median overall survival rate of subjects

    Measured: 26 months

Timeline

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

  1. First posted6 Dec 2018
  2. Study start20 Sep 2017
  3. Primary completionJun 2028 (estimated)
  4. Study completionDec 2028 (estimated)

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 2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
340 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03767348
Sponsor's protocol ID
RPL-001-16
Other IDs
2016-004548-12, 2024-511728-15-00, 2016
Acronym
IGNYTE
Status last verified
Feb 2026
First submitted
5 Dec 2018
Last updated
13 Feb 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • Wong MK, Milhem MM, Sacco JJ, Michels J, In GK, Munoz Couselo E, Schadendorf D, Beasley GM, Niu J, Chmielowski B, Wise-Draper TM, Bowles TL, Tsai KK, Lebbe C, Gaudy-Marqueste C, Middleton MR, Skolariki A, Samson A, Chesney JA, VanderWalde AM, Zakharia Y, Harrington KJ, Appleton E, Bommareddy PK, Zhu J, Viana M, Hou JW, Coffin RS, Robert C. RP1 Combined With Nivolumab in Advanced Anti-PD-1-Failed Melanoma (IGNYTE). J Clin Oncol. 2025 Nov 20;43(33):3589-3599. doi: 10.1200/JCO-25-01346. Epub 2025 Jul 8.

    PubMed 40627813

  • Thomas S, Kuncheria L, Roulstone V, Kyula JN, Mansfield D, Bommareddy PK, Smith H, Kaufman HL, Harrington KJ, Coffin RS. Development of a new fusion-enhanced oncolytic immunotherapy platform based on herpes simplex virus type 1. J Immunother Cancer. 2019 Aug 10;7(1):214. doi: 10.1186/s40425-019-0682-1.

    PubMed 31399043

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing RP1 and nivolumab in people with Non-Small Cell Lung Cancer (NSCLC) and Microsatellite Instability-High (MSI-H), run by Replimune, Inc. at 51 sites in 5 countries.

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 9 inclusion and 8 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 13 Feb 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 51 sites in United States, France, Spain, United Kingdom, Germany. 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 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?

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?

Percentage of adverse events (AEs) (time frame: 26 months). The study lists 5 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 NCT03767348, which also lists 2 linked publications.

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 13 Feb 2026.

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