An Open-Label, Multicenter, Phase I Study of RP2 as a Single Agent and in Combination with PD1 Blockade in Patients with Solid Tumors

Study Identifier:
RP2-001-18
CT.gov Identifier:
NCT04336241
EudraCT Identifier:
2018-003765-33
EU Trial (CTIS) Number:
2024-512866-32-00
Study Contact Information:
N/A
Recruitment Complete

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Study Summary

To evaluate RP2 alone and in combination with anti-PD1 therapy in mixed advanced solid tumors.

To evaluation of safety, biological activity and determination of the highest tolerated dose.

To determine the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D), as well as to evaluate preliminary efficacy.

To Assess initial safety and efficacy and determine the recommended phase 2 dose (RP2D) of RP2 alone and combined with nivolumab.

The tumor immune microenvironment (TIME) was analyzed by multi-plex (7 color 6-plex - CD8, PD-L1, PD-1, foxp3, CD68 and S100B) immunohistochemistry (IHC) of tumor biopsies using the Opal Human Panel (OHP) 6043 and by gene expression analysis using the NanoString IO360 panel.

To evaluate the safety and antitumor activity of the combination in pts with solid tumors, and is fully enrolled.

To safety, efficacy, and biomarker data of RP2 ± nivo.

To present updated safety and efficacy data of RP2 monotherapy and RP2 + nivolumab (nivo; anti–PD-1) in patients (pts) with uveal melanoma.

Responses were assessed using modified Response Evaluation Criteria in Solid Tumors version 1.1.

HLA typing was obtained from patient history when available. Correlations between baseline tumor PD-L1 and CD8 expression, HLA type, prior treatment with ipilimumab (ipi)/nivo, and HLA status—vs clinical response status—were assessed.

Responses were assessed per modified RECIST v1.1.Tumor biopsies and peripheral blood mononuclear cells were collected pre-treatment and at day 43 and were analyzed by immunohistochemistry (IHC) and/or sequencing of the CDR3β region of the T-cell receptor (TCR) by immunoSEQ.

Medical Condition
The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.
  • Unspecified Cancer
    • Phase
    The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
    I
    Sex
    Female & Male
    Age
    18+ years
    Study Drug
  • Drug: The dose escalation portion (part 1) will include up to 24 solid tumour participants dosed with RP2 in three dose level cohorts by direct or ultrasound guided injection into superficial, subcutaneous or nodal tumours and by imaging guided injection into deeper lesions including visceral lesions. In the dose escalation portion, participants will receive up to 5 doses of RP2 given every two weeks.
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  • Drug: There will also be a dose expansion portion (part 2) where up to 12 participants will receive a fixed dose of RP2, that is deemed to be safe in combination with Nivolumab (anti-PD-1 therapy).
  • Drug: Arm 1:
  • Drug: Intervention/treatment:
  • Drug: Arm 2:
  • Drug: Biological: nivolumab
  • Drug: SITC 2020:
  • Drug: SITC 2021:
  • Drug: AACR 2022:
  • Drug: Part-2:
  • Drug: ESMO 2022
  • Drug: ASCO 2023:
  • Drug: ASCO 2024:
    • Study Status
    Indicates the current recruitment status or the expanded access status
    Recruitment Complete

    Requirements information
    Inclusion criteria
    • Willing and able to participate and comply with all trial requirements and able to provide signed and dated informed consent prior to initiation of any trial procedures
    • Male or Female = 18 years of age
    • Patients with advanced or metastatic non-neurological solid tumors, who have progressed on standard therapy or cannot tolerate standard therapy, or for which there is no standard therapy preferred to enrolment in a clinical trial
    • Consent to provide archival tumour biopsy samples within 6 months, or a fresh tumour biopsy is needed. Patients must also consent to provide on-treatment biopsies as per protocol
    • At least one measurable and injectable tumor of = 1 cm in longest diameter (or shorter diameter for lymph nodes).
    • Women of child-bearing potential (WOCBP) must have a negative urine pregnancy test at screening and a negative urine pregnancy test prior to administration of each dose of RP2 or nivolumab
    • WOCBP must agree to use adequate birth control throughout their participation and for 3 months after RP2 alone and 5 months after nivolumab last study treatment
    • Males with partners of child-bearing potential must agree to use adequate birth control throughout their participation and for 3 months for RP2 alone and 7 months after nivolumab last study treatment
    • Have laboratory values (obtained = 28 days prior to first infusion day) in accordance with the study protocol
    • Have an Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1
    • Cohort 2a only:
    • Baseline ECG that does not show abnormalities according to the protocol
    • Baseline troponin < 0.06 ng/mL
    • Baseline oxygen saturation levels that do not show abnormalities according to the protocol
    • Cohort 2b and Part 3 only:
    • Patients in Cohort 2b should have histologically or cytologically confirmed diagnosis of advanced or metastatic uveal melanoma, lung cancer, breast cancer, or gastrointestinal cancers (including but not limited to colorectal cancer [CRC] [microsatellite stable], gastric cancer, gastroesophageal junction cancer, and oesophageal cancer) (n=30)
    • Patients with HCC and a diagnosis of hepatitis B must be off antiviral therapy for at least 4 weeks prior to enrollment.
    • Patients with acute or chronic hepatitis B or C must be expected to not require antiviral therapy during the RP2 treatment period.
    • Patients with HCC who have evidence of acute or chronic hepatitis C infection must have completed treatment for hepatitis C at least 1 month prior to study enrollment
    • Patients in Part 3 should have solid tumours (excluding skin cancers) that the investigator deems suitable for RP2 monotherapy, including at least 10 patients with liver metastases from prevalent tumour types (e.g. lung, breast [including recurrent chest wall], and gastrointestinal cancers [colorectal, gastric, and oesophageal cancers]) (n=15)
    • Patient has progressed during or after one to three prior systemic anticancer therapies for advanced or metastatic disease or during or within six months of receiving adjuvant therapy. Patients who, in the opinion of the investigator, are deemed not appropriate candidates for standard-of-care systemic anticancer therapy for advanced or metastatic disease, or who, after documented consultation with their treating physician, refuse standard-of-care systemic anticancer therapy may be eligible after discussion with the medical monitor
    • Key inclusion criteria include histologically confirmed advanced or metastatic non-neurological solid tumors, at least one measurable and injectable tumor of diameter > or = 1 cm, ECOG < or = 1, and adequate hematologic, hepatic, and renal function.
    • 2024 ASCO:
    • Age 21B years
    • Advanced or metastatic non- neurological solid tumors (including uveal melanoma)
    • progressed on or cannot tolerate standard therapy
    • At least 1 measurable and
    • injectable tumor 21 cm
    • ECOG ps 0-1
    Exclusion criteria
    • Prior treatment with an oncolytic virus therapy
    • History of viral infections according to the protocol
    • Systemic infection requiring IV antibiotics within 14 days prior to dosing
    • Prior complications with herpes infections
    • Chronic use of anti-virals
    • Systemic therapies for cancer within five half-lives or 4 weeks of first dose; whichever is shorter
    • Conditions that require certain doses of steroids (some doses and types will be permitted)
    • Known active brain metastases - previously treated brain metastases may be permitted
    • Major surgery = 2 weeks prior to starting study drug
    • Prior malignancy active with the previous 3 years; except for locally curable cancers that have apparently been cured
    • Female who has a positive urine pregnancy test or is breast-feeding or planning to become pregnant during study treatment and 90 days for RP2 alone or 5 months for RP2 and nivolumab after the last dose of treatment
    • Participation in another clinical study within 4 weeks prior to the first dose
    • History of myocarditis or congestive heart failure (as defined by the New York Heart Association Functional Classification III or IV), or unstable angina, serious uncontrolled cardiac arrhythmia, uncontrolled infection, or myocardial infarction within 6 months of randomization
    • History of allergy or sensitivity to study drug components
    • Has known psychiatric or substance abuse disorders that would interfere with cooperating with the requirements of the study
    • Part 2 patients only:
    • Participants with history of life-threatening toxicity related to prior immune therapy except those that are likely to re-occur with standard countermeasures
    • Treatment with botanical preparations within 2 weeks prior to treatment
    • Certain autoimmune diseases, some types will be permitted
    • History of interstitial lung disease
    • Severe hypersensitivity to another monoclonal antibody
    • Has received radiotherapy within 2 weeks of start of study treatment
    • Has received a live vaccine within 28 days prior to first dose of study drug
    • History of non-infectious pneumonitis
    • History or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study
    • Other serious or uncontrolled medical disorders
    • Cohort 2b and Part 3 (only for the subset of patients with liver metastases suitable and intended for injection)
    • Presence of liver metastases that are estimated to invade more than one-third of the liver
    • Macroscopic intravascular invasion into the main portal vein, hepatic vein or vena cava
    • Significant bleeding event within the last 12 months that places the patient at risk for intrahepatic intratumoral injection procedure based on investigator assessment
    • Prior chemoembolization, radioembolization, or other locoregional liver-directed procedures to the lesion selected for intratumoral injection
    • Exclusion criteria include prior treatment with oncolytic viruses, acute or chronic hepatitis B or C infection, and HIV infections.
    • 2024 ASCO:
    • Prior treatment with 01
    • History Of HBV, HCV, or HIV infection
    • Active significant herpetic infections/ prior complications of HSV-I infection
    • Active CNS metastases and/or carcinomatous meningitis
    • Major surgery Q weeks prior to starting study drug

    Clinical Study Information for Healthcare Providers

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    Study Locations

    Location
    Investigator
    Status
    Condition(s) Treated at Site
    Location
    START Madrid, Spain (CIOCC)
    Madrid, Spain, 28050
    Investigator
    Irene Moreno
    Status
    Recruitment Complete
    Condition(s) Treated at Site
    Unspecified Cancer