Clinical Trials

Inclusion Criteria - Part A:

• Subject is ≥ 18 years of age (at the time of signing the ICF) with non-curative recurrent and/or metastatic solid tumors including but not limited to breast cancer, bladder cancer, NSCLC, gastric cancer and ovarian cancer, who have progressed on standard treatments or for which a standard therapy is not available or is no longer effective.
• Subject has histologically and/or cytologically confirmed solid tumors.
• Subject has recurrent and/or metastatic non-curative HER2‒ve breast cancer (based on most recently analyzed biopsy) defined by ASCO-CAP guidelines as negative in situ hybridization test or an IHC status of 0, 1+, or 2+. If IHC is 2+, a negative in situ hybridization (FISH, CISH, or SISH) test is required by local laboratory testing.
  • For estrogen-receptor positive breast cancer performed by local laboratory:
    • Might have received prior hormonal treatments including combination with CDK4/6 inhibitors;
    • For pre-menopausal subjects LHRH agonists are allowed.
  • Adjuvant or neoadjuvant chemotherapy allowed.
• Subject has received a maximum of two lines of chemotherapy in the metastatic setting:
  • Prior treatment with checkpoint inhibitors and small molecules (targeted therapies) are allowed if not given with chemotherapy-based treatment.
• Subject has tumor that is positive for CD205 antigen (≥ 2+ in > 50% of tumor cells by IHC staining). The CD205 assay is a laboratory developed test, validated in a CAP/CLIA setting, and performed in a central CAP/CLIA certified laboratory.
• Subject has an ECOG performance status of 0-1.
• Subject has radiological documented measurable disease (i.e., at least 1 measurable lesion as per RECIST Version 1.1).
  • For breast cancer if no measurable disease is present, then at least 1 predominantly lytic bone lesion must be present.
• Subject has adequate organ functions, evidenced by the following:
  • AST (SGOT), ALT (SGPT) ≤ 2.5 x ULN, or ≤ 5 x ULN range if liver metastasis present;
  • Total bilirubin ≤ 1.5 x ULN;
  • Creatinine ≤ 1.5 x ULN;
  • Potassium within normal range (according to local lab), or correctable with supplements.
• Subject has adequate bone marrow function, evidenced by the following:
  • ANC ≥ 1.5 x 10^9 cells/L;
  • Platelets ≥ 100 x 10^9 cells/L;
  • Hemoglobin ≥ 9 g/dL.
• Subject understands and voluntarily signs an ICD prior to any study-related assessments/procedures are conducted.
• Subject is able to adhere to the study visit schedule and other protocol requirements.

Exclusion Criteria:

• Criteria number will not be used after protocol version 1.
• Subject has received any chemotherapy within 21 days prior to inclusion in the study.
• Subject has symptomatic visceral crisis requiring chemotherapy per Investigator judgment for non TNBC.
• Subject has received another investigational therapy within 28 days or 5 half-lives of randomization, whichever is shorter.
• Subject has not recovered from the acute toxic effects (CTCAE grade ≤ 1) of prior anticancer therapy, radiation, or major surgery/significant trauma (except alopecia or other toxicities not considered a safety risk for the subject at the Investigator’s discretion).
• Subject has had major surgery within 14 days prior to starting study treatment or has not recovered from major side effects.
• Subject has had radiotherapy ≤ 4 weeks or limited field radiation for palliation ≤ 2 weeks prior to starting study drug, and/or from whom ≥ 30% of the bone marrow was irradiated.
• Subject has a history of, or current symptomatic brain metastasis.
  • Subjects with asymptomatic brain metastases may participate in this study. The subject must have completed any prior local treatment for brain metastases ≥ 28 days prior to the start of study treatment (including radiotherapy and/or surgery) and must be receiving no or low stable dose corticosteroids.
• Subject has severe renal impairment (creatinine clearance < 30 mL/min).
• Subject has any other malignancy within 5 years prior to randomization, with the exception of adequately treated in situ carcinoma of the cervix, uterus, or non-melanomatous skin cancer (all treatment of which should have been completed 6 months prior to enrollment).
• Subject has a known or suspected hypersensitivity or other contraindication to any excipients used in the manufacture of OBT076.
• Subject has active or chronic corneal disorder or Sjogren’s syndrome.
• Subject has any ongoing skin disorders not controlled by specific treatment.
• Subject has significant active cardiac disease within the previous 6 months including unstable angina or angina requiring surgical or medical intervention, significant cardiac arrhythmia, or NYHA class 3 or 4 congestive heart failure.
• Subject has a known history or current diagnosis of HIV infection, unless on triple antiviral treatment with undetectable viral load.
• Subject has any significant medical condition, laboratory abnormality, or psychiatric illness that would, in the Investigator’s judgment, contraindicate subject participation in the study (e.g., history of thromboembolic event, cardiac dysfunction, chronic pancreatitis, chronic active hepatitis).
• Subject has any condition that confounds the ability to interpret data from the study.
• Subject is a female of childbearing potential [defined as a sexually mature woman who:
  • has not undergone hysterectomy (the surgical removal of the uterus) or bilateral oophorectomy (the surgical removal of both ovaries); or
  • has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time during the preceding 12 consecutive months)] and is not using any adequate form of birth control.
• Subject is lactating or breastfeeding.

Inclusion Criteria - Part B:

• Subject is ≥ 18 years of age (at the time of signing the ICF) who have progressed on standard treatments or for which a standard therapy is not available or is no longer effective.
• Subject has histologically and/or cytologically confirmed solid tumors.
• Subject has recurrent and/or metastatic non-curative HER2‒ve breast cancer (based on most recently analyzed biopsy) defined by ASCO-CAP guidelines as negative in situ hybridization test or an IHC status of 0, 1+, or 2+. If IHC is 2+, a negative in situ hybridization (FISH, CISH, or SISH) test is required by local laboratory testing. a) For estrogen-receptor positive breast cancer performed by local laboratory i) Might have received prior hormonal treatments including combination with CDK4/6 inhibitors. ii) For pre-menopausal subjects LHRH agonists are allowed. b) Adjuvant or neoadjuvant chemotherapy is allowed. 4) Subject with non-curative recurrent and/or metastatic solid tumors including put not limited to bladder cancer, gastric cancer, NSCLC and ovarian cancer for whom no other curative options are available 5) Subject has received maximum two lines of chemotherapy in the metastatic setting a) Prior treatment with checkpoint inhibitors and small molecules (targeted therapies) are allowed if not given with chemotherapy-based treatment. 6) Subject has tumor that is positive for CD205 antigen (≥ 2+ in ≥ 50% IHC) The CD205 assay is a laboratory developed test, validated in a CAP/CLIA setting, and performed in a central CAP/CLIA certified laboratory.
• Subject has an ECOG performance status of 0-1. 8) Subject has radiological documented measurable disease (i.e., at least 1 measurable lesion as per RECIST Version 1.1).
  • For breast cancer if no measurable disease is present, then at least 1 predominantly lytic bone lesion must be present.
• Subject has adequate organ functions, evidenced by the following:
  • a) AST (SGOT), ALT (SGPT) ≤ 2.5 x ULN, or ≤ 5 x ULN range if liver metastasis present. b) Total bilirubin ≤ 1.5 x ULN. c) Creatinine ≤ 1.5 x ULN. d) Potassium within normal range (according to local lab), or correctable with supplements. 10) Subject has adequate bone marrow function, evidenced by the following: a) ANC ≥ 1.5 x 109 cells/L. b) Platelets ≥ 100 x 109 cells/L. c) Hemoglobin ≥ 9 g/dL. 11) Subject understands and voluntarily signs an ICD prior to any study-related assessments/procedures are conducted. 12) Subject is able to adhere to the study visit schedule and other protocol requirements.

Exclusion Criteria - Part B:

• Criteria number will not be used after protocol version 1.
• Subject has received any chemotherapy within 21 days prior to inclusion in the study.
• Subject has symptomatic visceral crisis requiring chemotherapy per Investigator judgment for non TNBC.
• Subject has received another investigational therapy within 28 days or 5 half-lives of randomization, whichever is shorter.
• Subject has not recovered from the acute toxic effects (CTCAE grade ≤ 1) of prior anticancer therapy, radiation, or major surgery/significant trauma (except alopecia or other toxicities not considered a safety risk for the subject at the Investigator’s discretion).
• Subject has had major surgery within 14 days prior to starting study treatment or has not recovered from major side effects.
• Subject has had radiotherapy ≤ 4 weeks or limited field radiation for palliation ≤ 2 weeks prior to starting study drug, and/or from whom ≥ 30% of the bone marrow was irradiated.
• Subject has a history of, or current symptomatic brain metastasis.
• Subjects with asymptomatic brain metastases may participate in this study. The subject must have completed any prior local treatment for brain metastases ≥ 28 days prior to the start of study treatment (including radiotherapy and/or surgery) and must be receiving no or low stable dose corticosteroids.
• Subject has severe renal impairment (creatinine clearance < 30 mL/min).
• Subject has any other malignancy within 5 years prior to randomization, with the exception of adequately treated in situ carcinoma of the cervix, uterus, or non-melanomatous skin cancer (all treatment of which should have been completed 6 months prior to enrollment).
• Subject has a known or suspected hypersensitivity or other contraindication to any excipients used in the manufacture of OBT076.
• Subject has active or chronic corneal disorder or Sjogren’s syndrome.
• Subject has any ongoing skin disorders not controlled by specific treatment.
• Subject has significant active cardiac disease within the previous 6 months including unstable angina or angina requiring surgical or medical intervention, significant cardiac arrhythmia, or NYHA class 3 or 4 congestive heart failure.
• Subject has a known history or current diagnosis of HIV infection, unless on triple antiviral treatment with undetectable viral load.
• Subject has any significant medical condition, laboratory abnormality, or psychiatric illness that would, in the Investigator’s judgment, contraindicate subject participation in the study (e.g., history of thromboembolic event, cardiac dysfunction, chronic pancreatitis, chronic active hepatitis).
• Subject has any condition that confounds the ability to interpret data from the study.
• Subject is a female of childbearing potential [defined as a sexually mature woman who:
  • has not undergone hysterectomy (the surgical removal of the uterus) or bilateral oophorectomy (the surgical removal of both ovaries); or
  • has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time during the preceding 12 consecutive months)] and is not using any adequate form of birth control.
• Subject is lactating or breastfeeding.