A Study of ART0380 for the Treatment of Advanced or Metastatic Solid Tumors

Inclusion Criteria41

• Signed informed consent
• Discontinued all previous treatments for cancer for at least 21 days or 5 half-lives, whichever is shorter, and recovered from the acute effects of therapy to CTCAE Grade ≤1. Palliative radiotherapy must have completed 1 week prior to start of study treatment.
• If patients have a known germline BRCA mutation or a cancer with a somatic BRCA mutations or which is HRD positive and for which there is an approved PARP inhibitor, participants should have received such treatment before participating in the study unless contra-indicated
• At least 1 radiologically evaluable lesion (measurable and/or non-measurable) that can be assessed at baseline and is suitable for repeated radiological evaluation by RECIST v1.1 or Prostate Cancer Working Group-3 Guidelines (PCWG-3)
• Acceptable hematologic, renal, hepatic, and coagulation functions independent of transfusions and granulocyte colony-stimulating factor
• Non-irradiated tumor tissue sample (archival or newly obtained core biopsy of a tumor lesion) available for submission for analysis.
• Female patients of childbearing potential and male patients with female partners of childbearing potential are required to use highly effective contraception plus one barrier method during their participation in the study and for 7 months and 5 months respectively following the last dose. For male and female patients given gemcitabine or irinotecan, highly effective contraception plus one barrier method must be used from study entry until 6 months after the last dose of study treatment. Male patients are required to refrain from donating sperm and female patients are required to refrain from donating eggs, during their participation in the study and for 6 months following last dose.
• Estimated life expectancy of ≥12 weeks
• Reliable and willing to make themselves available for the duration of the study and are willing to follow study procedures
• Performance status of 0-1 on the ECOG Scale
• Advanced or metastatic cancer which is refractory to standard therapies, or for which no standard therapies exist, or for which the investigator feels no other active therapy is required for the duration of the study
• Performance status of 0-1 on the Eastern Cooperative Oncology Group (ECOG) scale
• •Advanced or metastatic cancer for which gemcitabine is an appropriate treatment. Prior treatment with gemcitabine is permitted.
• Advanced or metastatic cancer for which irinotecan is an appropriate treatment. Prior treatment with irinotecan is permitted.
• For food effect cohort only: Patients must be able to eat a high-fat meal within a 30 minute period, as provided by the study site.
• Patients with advanced or metastatic solid tumors with alterations to the ATM gene likely to predict for loss of ATM protein
• Have at least 1 measurable lesion assessable using standard techniques by RECIST v1.1
• For France only ART0380 Monotherapy; Patient that is not eligible for curative treatment, for whom all standard of care therapies have failed and no therapies known to provide clinical benefit are available.
• Combination arms; Patients for which irinotecan is an appropriate treatment. Prior treatment with irinotecan is permitted.
• For Spain only ART0380 Combination therapy, Patient that is not eligible for curative treatment, for whom standard of care therapies have failed.
• Patients with a known germline BRCA mutation, or a cancer with a known somatic BRCA mutation, or which is known to be HRD positive, and for which there is an approved PARP inhibitor should have received such treatment before participating in the study, unless contra-indicated.
• Females with histologically-confirmed diagnosis of high grade serous carcinoma of the ovary, fallopian tube or primary peritoneum that is not amenable to curative therapy
• Platinum-resistant disease. Patients must not have had primary platinum-refractory disease (disease that progressed during first-line platinum-based therapy).
• No more than one prior regimen in the platinum-resistant setting. Hormonal therapies and antiangiogenic therapies (as single agents) and PARP inhibitors used as maintenance therapy are not considered as separate lines of therapy. Patients should have previously received bevacizumab and chemotherapy unless contra-indicated.
• Have not received prior treatment with gemcitabine unless administered in combination with a platinum with no disease progression within 12 months after completion of that regimen
• Have at least 1 measurable lesion assessable using standard techniques by RECIST v1.1
• Persistent or recurrent endometrial cancer with biological selection.:
• Patients should have received taxane/platinum chemotherapy, unless contraindicated.
• Measurable disease.
• Advanced or metastatic solid cancers of any histology with biological selection
• If a PD-1/PDL-1 inhibitor (eg, pembrolizumab) is approved and available for the patient's cancer, the patient should have received such treatment before participating in this study.
• Radiologically evaluable disease
• Performance status of 0-1 on the ECOG scale
• Metastatic CRC with alterations to the ATM gene
• Participants should have previously received appropriate prior lines of therapy in this setting.
• Have at least 1 measurable lesion assessable using standard techniques by RECIST v1.1.
• Patients have received a maximum of 2 prior chemotherapy regimens for the treatment of CRC and have demonstrated progressive disease or intolerance to their last regimen.
• Metastatic or locally advanced PDAC or acinar cell carcinoma with alterations to the ATM gene
• Participants must have received a maximum of 1 prior chemotherapy regimen for the treatment of the advanced disease and have demonstrated progressive disease or intolerance to this regimen OR have received neoadjuvant/adjuvant therapy with recurring occurring \<6 months following completion of this treatment.
• Have at least 1 measurable lesion assessable using standard techniques by RECIST v1.1. Previously irradiated lesions may not be considered target lesions.
• Serum albumin ≥3g/dL within 7 days prior to first dose.