A Phase 1, Open-Label, Dose-Escalation Study of RM-1995 Photoimmunotherapy Alone or in Combination with pembrolizumab in Patients with Advanced or Recurrent Solid Tumor with Liver Metastasis
Phase I trial sponsored by Rakuten Medical K.K.
Okuda Daisuke
Rakuten Medical K.K.
Futakotamagawa Rise Office, 2-21-1 Tamagawa, Setagaya-ku, Tokyo
+81-3-4405-2187
daisuke.okuda@rakuten-med.com
Customer Support center
Rakuten Medical K.K.
Futakotamagawa Rise Office, 2-21-1 Tamagawa, Setagaya-ku, Tokyo
+81-120-169-373
info.jp@rakuten-med.com
Recruiting
April. 01, 2023
June. 14, 2023
34
Interventional
single arm study
open(masking not used)
uncontrolled control
single assignment
treatment purpose
- Provide written informed consent.
- Male or female >= 18 years of age at the time of informed consent.
- Have advanced or recurrent solid tumor with a hepatic metastasis diagnosed as histologically malignant.
- Unresponsive or intolerant to standard therapy for each type of cancer, as evaluated by the Investigators, or unwilling to be treated with the relevant standard treatments for some reason.
- Have at least 1 hepatic lesion which can be illuminated using a needle catheter or cylindrical diffuser.
- Before study treatment initiation (C1D1) and on 21 days after the first administration of RM-1995, tumor samples can be collected from a hepatic lesion with planned illumination treatment as well as a hepatic lesion or extrahepatic lesion (including primary lesion) with no illumination treatment planned. Consented to provide enough fresh and FFPE tumor tissue samples for exploratory studies of pharmacodynamic biomarkers.
- Eastern Cooperative Oncology Group (ECOG) performance status is 0 to 1 at enrollment.
- Have sufficient organ function (all laboratory examination at screening should be done within 14 days before enrollment.
- Women of childbearing potential (WOCBP)who are not pregnant or breastfeeding. Agree to use one of the two highly effective contraceptive methods or refrain from sexual intercourse, as well as not to provide any eggs (ova and oocytes) for reproductive purposes during the study period and for at least 120 days after final administration of the study drug.
- Male patients who are infertile, agree to use appropriate contraceptive methods, or refrain from sexual intercourse. Agree not to provide sperms for reproductive purposes from the first study treatment to at least 120 days after final administration of the study drug.
- Treated with anti-cancer treatment for a specific period, as described below.
Patients who are treated with chemotherapy or hormone therapy within 2 weeks prior to study treatment initiation or 5 times the half-life of the drug
Patients who are treated with radiation therapy or other local therapy within 2 weeks prior to study treatment initiation.
Patients who are treated with immunotherapy within 6 weeks prior to study treatment initiation or 5 times the half-life of the drug.
- Patients who have not recovered (i.e., not Grade =< 1 at enrollment) from anti-cancer treatment-related toxicity.
- Patients with a history of discontinuation of immunotherapy due to Grade >= 3 toxicity evaluated by the Investigator as related to the mechanism of action of the study drug (and pembrolizumab, in cases of combination therapy).
- Patients with a history or complication of interstitial lung disease that requires systemic steroid therapy.
- Patients who are judged by the Investigator to have a tumor at a site where a serious complication may occur due to needle catheter puncture and irradiation with a cylindrical diffuser.
- Patients with a CNS primary malignancy or CNS metastasis.
- Patients with carcinomatous meningitis.
- Patients who developed malignancy other than the target disease within 5 years before study initiation.
- Patients with a history and complications of serious cardiovascular disease.
- Patients with any of the following conditions related to the heart.
QT interval, QTc interval is > 480 msec.
Patients who have a history or complication of congenital QT prolongation syndrome or torsade de pointes.
- Known to have clinically significant hepatic disease.
- Known to have ascites that would make laser-illumination to the hepatic lesion difficult.
- Have a history of allogenic bone marrow transplantation or solid organ transplantation.
- Need to be treated with systemic steroids or systemic immunosuppressants for the treatment of autoimmune disease within 90 days before enrollment.
- Known history of testing positive for human immunodeficiency virus infection or acquired immunodeficiency syndrome-related diseases.
- Known detection of active or latent hepatitis B or hepatitis C.
- Known history of testing positive for qualitative HTLV-1.
- Received an attenuated live vaccine within 4 weeks before initial RM-1995 treatment (for treatment with RM-1995 PIT alone) or initial pembrolizumab treatment (for treatment with RM-1995 PIT in combination with pembrolizumab), or anticipated to receive an attenuated live vaccine during the study period.
- Require anti-platelet drugs, anticoagulants or thrombolytic drugs during the study period, which would increase the risk of bleeding.
- Patients with uncontrolled complications.
- Patients with active infections.
- Patients who underwent major surgery within 28 days prior to initial RM-1995 treatment (for treatment with RM-1995 PIT alone) or initial pembrolizumab treatment (for treatment with RM-1995 PIT in combination with pembrolizumab) or anticipated to undergo major surgery unrelated to the study intervention during the study period.
- Have a history of severe allergic, anaphylactic, or other hypersensitivity reactions to RM-1995, basiliximab, pembrolizumab, or any component of other monoclonal antibodies.
- Have a history of treatment with RM-1995 PIT or who are deemed inappropriate as candidates to receive RM-1995 PIT or pembrolizumab (for combination therapy with RM-1995 PIT and pembrolizumab) by the Investigator.
- Patients who are reasonably suspected to have diseases or conditions that contraindicate the use of study treatment, may affect the interpretation of study results, or may pose a high risk for complications based on other diseases, metabolic disorders, physical examination, or laboratory findings.
- Female patients who are pregnant, breast-feeding or deemed to be possibly pregnant by pregnancy test positive and a physician's examination.
- Patients who do not or cannot comply with the provisions in the protocol judged by the Investigator.
18age old over
No limit
Both
Advanced or recurrent solid tumors with one or more hepatic metastasis
Phase Ia: RM-1995 administration at a dose range of 0.25 to 2.0 mg/kg, followed 24 +- 4 hours later by laser illumination of the target hepatic lesion using a cylindrical diffuser at a fixed dose of 100 J/cm.
Phase Ib: RM-1995 administration at an optimal dose determined in the Phase 1a part, followed 24 +- 4 hours later by laser illumination of a target liver metastatic lesion using a cylindrical diffuser at a dose of 200 or 300 J/cm.
Phase Ic: pembrolizumab is administered at the fixed dose of 200 mg IV. This is followed 7 days after pembrolizumab administration, on CxD8, by RM-1995 administered at the optimal dose determined based on RM-1995 PIT monotherapy in the Phase 1b part. 24 +- 4 hours later, target liver metastatic lesions are illuminated using a cylindrical diffuser, at the optimal laser dose determined based on RM-1995 PIT monotherapy in the Phase 1b part.
- Onset of dose-limiting toxicity (DLT)
- Types, frequency and severity of adverse event (AE)
- Type, frequency, and severity of medical device-related AEs associated with the use of PIT690.4-2500 lasers, cylindrical diffusers, and needle catheters
Rakuten Medical K.K.
Japan Agency for Medical Research and Development
Not applicable
National Cancer Center Hospital Institutional Review Board
