Be ≥18 years of age (or the legal age of majority in the jurisdiction in which the study is taking place, whichever is greater) at the time of informed consent.
Part 1: Individuals with a diagnosis of locally advanced or metastatic disease (solid tumors except tumors of the CNS) who have previously received available standard therapy and progressed, or cannot tolerate standard therapy, or for whom there is no standard of care per regional guidelines. Per investigator assessment, the individual’s disease burden should not require immediate systemic therapy, particularly for extrahepatic disease. Individuals who have previously declined standard therapy in consultation with their health care professional may participate as long as documentation of the medical endorsement for their decision is provided. Participants who will be evaluated for DLT must have tumor lesion(s) in the liver that is measurable as per RECIST 1.1 and amenable for JNJ-1761981 ER administration, and of sufficient volume to allow placement of the needed number of solid depots per dose level.
Part 2 Cohort A: Individuals with histologically or cytologically confirmed NSCLC with metastatic disease in the liver who have been previously treated with standard of care sequentially or in combination, or declined such therapy (with documentation of the medical endorsement for their decision) including:
Anti-PD-1/PD-L1 (except EGFR, ALK, or other known driver mutations with approved therapy)
Targeted therapy (EGFR, ALK, or other known driver mutations with approved therapy)
Platinum-based chemotherapy (all NSCLC)
Participants must have tumor lesion(s) in the liver that is measurable as per RECIST 1.1 and amenable for JNJ-1761981 ER administration at the planned volumetric dose and without exceeding the total dose level(s) deemed safe by SET in Part 1
ECOG performance status of Grade 0 or 1
Hematology laboratory parameters within the following range, independent of transfusion within 7 days, or granulocyte colony stimulating-factor within 2 weeks prior to first dose of study treatment:
Criterion Modified per Amendment 1
6.1 Adequate liver function:
Adequate renal function with eGFR ≥60 mL/min calculated using MDRD formula
Part 2 Cohort A participants planned to receive cetrelimab (participants not meeting this criterion may still be enrolled in the study but cannot receive cetrelimab): Thyroid function laboratory values within normal range. Note: If TSH is not within normal limits, the participant may still be eligible if T3 (total or free) and free T4 are within normal limits.
A participant of childbearing potential must practice at least 2 highly effective methods of contraception throughout the study and through 14 months (for women) and 11 months (for men) after the last dose of JNJ-1761981 ER or 5 months after the last dose of cetrelimab or other anti-PD(L)1 treatment, whichever is later. Note: If the participant becomes of childbearing potential after the start of the study, the participant must comply with this criterion.
A participant of childbearing potential must have a negative highly sensitive serum (eg, β-hCG) pregnancy test at screening and within 72 hours of the first dose of study treatment and must agree to further serum or urine pregnancy tests during the study.
A participant using oral contraceptives must use an additional barrier contraceptive method.
A participant must agree not to be pregnant, breastfeed, or are planning to become pregnant while enrolled in this study and through 14 months after the last dose of JNJ 1761981 ER or 5 months after the last dose of cetrelimab or other anti-PD(L)1 treatment, whichever is later.
A participant must agree not to donate gametes (ie, eggs or sperm) or freeze for future use for the purposes of assisted reproduction during the study and through 14 months (for women) and 11 months (for men) after the last dose of JNJ-1761981 ER or 5 months after the last dose of cetrelimab or other anti-PD(L)1 treatment, whichever is later. Participants should consider preservation of gametes prior to study treatment as anti- cancer treatments may impair fertility.
A participant must wear a condom when engaging in any activity that allows for passage of ejaculate to another person during the study and for 11 months after the last dose of JNJ-1761981 ER or 5 months after the last dose of cetrelimab or other anti-PD(L)1 treatment, whichever is later. A participant who is vasectomized must still use a condom (with or without spermicide). If the participant’s partner is of childbearing potential, the participant must use condoms with spermicide and the partner of the participant must also be practicing a highly effective method of contraception.
A participant must agree not to plan to father a child while enrolled in this study or within 11 months of the last dose of JNJ-1761981 ER or 5 months after the last dose of cetrelimab or other anti-PD(L)1 treatment, whichever is later.
Must sign an ICF indicating that the participant understands the purpose of, and procedures required for, the study and is willing to participate in the study.
Be willing and able to adhere to the lifestyle restrictions specified in this protocol.
Active symptomatic disease involvement of the central nervous system (eg, primary central nervous system tumors, metastases, leptomeningeal disease) with the exception of brain metastases that are (1) definitively, locally treated AND (2) clinically stable and asymptomatic for >2 weeks without therapeutic dose of steroids (≤10 mg prednisone or equivalent is allowed as part of ongoing taper).
rior or concurrent second malignancy (other than the disease under study) that due to natural history or treatment is likely to interfere with any study endpoints of safety or the antitumor activity of the study treatment(s). Consultation with sponsor is required in such cases prior to enrollment.
Toxicity related to prior anticancer therapy that has not returned to Grade ≤1 or baseline levels (except for alopecia, vitiligo, Grade ≤2 peripheral neuropathy, and endocrinopathies that are stable on hormone replacement, which may be Grade 2).
Active bleeding diathesis or requirement for therapeutic anticoagulation that cannot be interrupted or altered for procedures.
Criterion Modified per Amendment 1
Venous thromboembolic events (eg, pulmonary embolism) within 1 month prior to the first dose of study treatment.
Known allergies, hypersensitivity, or intolerance to cisplatin, JNJ-1761981 ER or PLGA (refer to the IB for JNJ-1761981 ER).
Had major surgery (eg, requiring general anesthesia) within 2 weeks before the first dose of study treatment, or will not have fully recovered from surgery prior to the first dose. Participants with recent or planned surgical procedures utilizing only local anesthesia may participate.
Lesions invading or adjacent to major blood vessels or other critical structures (eg, airways) not suitable for injection. Equivocal cases will be assessed on an individual basis. A discussion between the administering physician and the sponsor medical monitor is required for equivocal cases.
Any prior anticancer therapy within 30 days before the first dose of study treatment
Received an investigational pharmaceutical intervention or used an invasive investigational medical device within 30 days before the planned first dose of study treatment.
Active hepatitis of infectious origin.
Seropositive for hepatitis B: defined by a positive test for HbsAg. Participants with resolved infection (ie, participants who are HbsAg negative with positive anti-HBc) must be screened using RT-PCR measurement of HBV DNA levels. Those who are RT-PCR positive will be excluded. Participants with serologic findings suggestive of HBV vaccination (anti-HBs positivity as the only serologic marker) AND a known history of prior HBV vaccination, do not need to be tested for HBV DNA by RT-PCR.
Known active hepatitis C infection or positive serologic testing for hepatitis C virus (anti-HCV) antibody.
Other clinically active liver disease of infectious origin.
HIV infection: Participants on effective anti-retroviral therapy with undetectable viral load within 6 months of the first dose of study treatment are eligible for this trial. For participants to be treated with cetrelimab.
Active infection or condition that requires treatment with systemic anti-infective agents (eg, antibiotics, antifungals, or antivirals) within 7 days prior to the first dose of study treatment or chronic use of anti-infective agents. Note: Intermittent use of topical anti-infective agents is not exclusionary
Any condition for which, in the opinion of the investigator, participation would not be in the best interest of the participant (eg, compromise the well-being) or that could prevent, limit, or confound the protocol-specified assessments.
Additional Exclusion Criteria for Participants in Part 2 Cohort A to be treated with cetrelimab. Participants meeting any of the criteria below may still be enrolled in the study, but cannot receive cetrelimab.
History of immune related AEs (irAEs) from prior anticancer therapy leading to treatment discontinuation, except for endocrinopathies that are stable on hormone replacement.
Active autoimmune disease that requires systemic immunosuppressive medications (eg, chronic corticosteroid, methotrexate, or tacrolimus) within the 12 months prior to signing consent.
History of non-infectious pneumonitis or interstitial lung disease that required systemic treatment with corticosteroids, or requirement for continuous supplemental oxygen use to maintain adequate oxygenation.
History of solid organ or hematologic stem cell transplantation.
Received or plans to receive any live vaccine within 28 days before the first dose of study treatment. Non-live or non-replicating vaccines approved (eg, influenza) or authorized for emergency use (eg, COVID-19) by local health authorities are allowed.
Known allergies, hypersensitivity, or intolerance to cetrelimab or its excipients (refer to the IB for cetrelimab) OR to other anti-PD(L)-1 antibody proposed for use or its excipients.
History of Grade 3 or higher toxic effects during prior treatment with immunotherapy or requirement of anti-TNF or anti-IL-6 agents to manage AEs from prior treatment with immunotherapy.
History of allergy to protein-based therapies or history of any significant drug allergy (such as anaphylaxis, hepatotoxicity, or immune-mediated thrombocytopenia or anemia).