BALSTILIMAB for Metastatic colorectal cancer (pMMR/MSS) | Metastatic gastrointestinal cancers

Inclusion criteria

• {"criterion_text":"- Main Study: Signed and dated informed consent obtained before undergoing any study-specific procedure\n- Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 1\n- Anticipated life expectancy ≥ 3 months\n- Adequate hematologic and end organ function, defined by the following laboratory results, obtained within 7 days before first dose of study drug treatment: 1. Hemoglobin ≥ 10 g/dL, platelet count ≥100,000/mm3, ANC ≥1500/mm3 2. Creatinine clearance ≥ 50 mL/min 3. Amylase and lipase ≤ 1.5 × ULN 4. Serum bilirubin ≤ 1.5× ULN 5. AST, ALT, and ALP ≤ 2.5 × ULN with the following exceptions: - Patients with documented liver metastases: AST and/or ALT ≤ 5 × ULN 6. INR and PTT ≤ 1.5 × ULN. - Patients who are on therapeutic doses of anti-coagulants should be on a stable dose for 28 days, with stable INR and PTT values. 7. Serum albumin ≥ 3.0 g/dL\n- Ability e and willingness to participate and comply with the requirements of the entire study\n- Study Extension_Cohort A and B: Signed and dated informed consent obtained before undergoing any study-specific procedure\n- Study Extension_Cohort A and B: Male or female aged ≥18 years\n- Body weight > 40kg\n- Histologically proven advanced-stage unresectable adenocarcinoma of the stomach or the GEJ\n- Stage IV (according to the American Joint Committee on Cancer definition)\n- Available CPS or available tissue to perform CPS assessment: Cohort A: CPS≥5 - Cohort B CPS<5\n- Male or female aged ≥18 years\n- Failure to at least one prior line of chemotherapy for metastatic disease, given with or without trastuzumab, with or without anti-PD-1. In alternative, early disease recurrence after surgery with neo-adjuvant and/or adjuvant chemotherapy (within 6 months of the last administration of chemotherapy) or progression during neo-adjuvant and/or adjuvant chemotherapy (containing fluoropyrimidine and a platinum derivative).\n- Presence of measurable disease per RECIST v1.1 (based on imaging within 28 days from first study drug administration). Patients must have at least one \"target lesion\" to be used to assess response, as defined by RECIST v1.1\n- Naïve to EP4 receptor antagonists\n- Availability of adequate and sufficient baseline tumour tissue sample (archival or newly obtained biopsy)\n- Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 1\n- Anticipated life expectancy ≥ 3 months\n- Adequate hematologic and end organ function, defined by the following laboratory results, obtained within 7 days before first dose of study drug treatment: 1. Hemoglobin ≥ 10 g/dL, platelet count ≥100,000/mm3, ANC ≥1500/mm3 2. Creatinine clearance ≥ 50 mL/min 3. Amylase and lipase ≤ 1.5 × ULN 4. Serum bilirubin ≤ 1.5× ULN 5. AST, ALT, and ALP ≤ 2.5 × ULN with the following exceptions: - Patients with documented liver metastases: AST and/or ALT ≤ 5 × ULN 6. INR and PTT ≤ 1.5 × ULN. - Patients who are on therapeutic doses of anti-coagulants should be on a stable dose for 28 days, with stable INR and PTT values. 7. Serum albumin ≥ 3.0 g/dL\n- Ability e and willingness to participate and comply with the requirements of the entire study\n- Study Extension_Cohort C: Signed and dated informed consent obtained before undergoing any study-specific procedure\n- Study Extension_Cohort C: Male or female aged ≥18 years\n- ESC - Histologically confirmed diagnosis of adenocarcinoma originating from the colon or rectum, with known RAS and BRAF mutational status as assessed per standard practice. EXP - Histologically confirmed diagnosis of adenocarcinoma originating from the colon or rectum, with known RAS and BRAF mutational status as assessed per standard practice. For patients included in the Expansion part only: PD-L1 CPS or adequate tissue to perform PD-L1 CPS assessment should be available.\n- Body weight > 40kg\n- Histologically proven advanced-stage unresectable GI cancer other than CRC and GC\n- Stage IV (according to the American Joint Committee on Cancer definition)\n- Failure to at least one prior line of chemotherapy for metastatic disease, given with or without trastuzumab, with or without anti-PD-1. In alternative, early disease recurrence after surgery with neo-adjuvant and/or adjuvant chemotherapy (within 6 months of the last administration of chemotherapy) or progression during neo-adjuvant and/or adjuvant chemotherapy (containing fluoropyrimidine and a platinum derivative).\n- Presence of measurable disease per RECIST v1.1 (based on imaging within 28 days from first study drug administration). Patients must have at least one \"target lesion\" to be used to assess response, as defined by RECIST v1.1\n- Naïve to EP4 receptor antagonists\n- Availability of adequate and sufficient baseline tumour tissue sample (archival or newly obtained biopsy)\n- Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 1\n- Anticipated life expectancy ≥ 3 months\n- Adequate hematologic and end organ function, defined by the following laboratory results, obtained within 7 days before first dose of study drug treatment: 1. Hemoglobin ≥ 10 g/dL, platelet count ≥100,000/mm3, ANC ≥1500/mm3 2. Creatinine clearance ≥ 50 mL/min 3. Amylase and lipase ≤ 1.5 × ULN 4. Serum bilirubin ≤ 1.5× ULN 5. AST, ALT, and ALP ≤ 2.5 × ULN with the following exceptions: - Patients with documented liver metastases: AST and/or ALT ≤ 5 × ULN 6. INR and PTT ≤ 1.5 × ULN. - Patients who are on therapeutic doses of anti-coagulants should be on a stable dose for 28 days, with stable INR and PTT values. 7. Serum albumin ≥ 3.0 g/dL\n- Stage IV (according to the American Joint Committee on Cancer definition)\n- Ability e and willingness to participate and comply with the requirements of the entire study\n- Presence of measurable disease per RECIST v1.1 (based on imaging within 28 days from first study drug administration). Patients must have at least one \"target lesion\" to be used to assess response, as defined by RECIST v1.1\n- ESC - Disease progression after at least two standard treatment lines for mCRC, including fluoropyrimidines, oxaliplatin and irinotecan and, if RAS and BRAF wild-type, cetuximab or panitumumab or, intolerance or refusal of chemotherapy regimens for mCRC\n- Naïve to any antibody/drug targeting T-cell co-regulatory proteins (immune checkpoints inhibitors) and EP4 receptor antagonists\n- ESC - Availability of adequate and sufficient baseline tumour tissue sample (archival or newly obtained biopsy) EXP - Availability of adequate and sufficient newly obtained fresh tumour tissue sample collected after ICF during the screening period and before the treatment starts. In case the biopsy collection is not feasible, according to Investigator judgement or patient decision, archival biopsy or surgical sample can be accepted after discussion with the Sponsor.\n- pMMR/MSS defined as CRC with all 4 MMR proteins intact and/or with instability at ≤1/5 locus (or 30% of loci if larger panel of markers are assayed)"}

Exclusion criteria

• {"criterion_text":"- Main and Extension Study: Additional malignancy that progressed or required active treatment within the last 2 years. Exceptions include basal cell carcinoma of the skin, superficial bladder cancer, squamous cell carcinoma of the skin that has undergone potentially curative therapy with no evidence of recurrence for 5 years since initiation of that curative therapy, or carcinoma in situ (breast carcinoma, cervical cancer)\n- History of stroke, reversible ischemic neurological defect, or transient ischemic attack within 6 months before enrolment\n- Uncontrolled ventricular arrhythmia\n- Congestive heart failure (New York Hearth Association class ≥II)\n- Poorly controlled hypertension\n- Confirmed infection with SARS-CoV-2 as documented by molecular testing at nasopharyngeal swab (only if required by the epidemiological situation)\n- HIV infection\n- Active tuberculosis\n- Acute or chronic viral hepatitis B or C infection\n- Any severe infection within 14 days before Cycle 1 Day 1\n- Active autoimmune disease in the past 2 years\n- Active brain tumour, metastasis or leptomeningeal metastases. Patients with brain metastases are eligible if these have been treated and there is no magnetic resonance imaging (MRI except where contraindicated in which CT scan is acceptable) evidence of progression for at least 8 weeks after treatment is complete and within 28 days prior to first dose of study drug administration. Cases should be discussed with the Sponsor. There must also be no requirement for immunosuppressive doses of systemic corticosteroids (>10mg/day prednisone equivalents) for at least 2 weeks prior to study drug administration\n- History of allogenic tissue/solid organ transplant (including allogeneic bone marrow transplantation)\n- History of immunodeficiency\n- History or presence of interstitial lung disease or history of pneumonitis that has required oral or iv corticosteroids.\n- History of gastric/duodenal ulcers, colitis and/or gastrointestinal bleeding\n- History of severe gastrointestinal adverse reactions\n- History of hypersensitivity reactions to fully human monoclonal antibodies, Grade ≥ 3 according to NCI CTCAE Version 5.0\n- History of anaphylaxis, or uncontrolled asthma\n- Allergy/hypersensitivity/intolerance to any component of CR6086 or AGEN2034\n- Any other clinically relevant disease and condition, including psychiatric or substance abuse disorders, that, in the opinion of the Investigator, may jeopardize efficacy or safety assessments, confound the result of the trial or may compromise the patient’s safety during trial participation\n- Administration of a live, attenuated vaccine within 28 days before Cycle 1 D1\n- Major surgery within 28 days before Cycle 1 Day 1 or anticipation of needing such procedure during the trial\n- Systemic steroid therapy or any other form of immunosuppressive therapy within 7 days before screening\n- Regular use of any illicit drugs or recent history (within the last year) of substance abuse (including alcohol)\n- Participation in a study with an investigational drug or medical device within 28 days before Cycle 1 Day 1\n- Inability to swallow medications\n- Malabsorption conditions\n- For women of childbearing potential:  Pregnancy (i.e. positive pregnancy test at Screening) or breastfeeding  Failure to agree to practice a highly effective method of contraception (see Section 12.4), from enrolment up to at least 120 days after the last IMP intake  expecting to conceive within the projected duration of the trial, starting with the screening visit through 120 days after the last dose of study treatment\n- For sexually active men with a female partner of childbearing potential: failure to agree to use condom (see Section 12.4) and refrain from donating sperm from enrolment up to at least 120 days after the last IMP intake\n- Patients who are legally incapacitated or has limited legal capacity\n- Study Extension only: Presence of portal hypertension\n- Presence of oesophageal varices\n- Treatment with any systemic or localized anti-cancer therapy, including chemotherapy, biological therapy, radiotherapy, or hormonal therapy within 28 days before initiation of Cycle 1 Day 1 or expected to required such a treatment during the trial\n- Presence of gastric infiltration, severe gastritis, duodenal or gastric ulcer, or any other condition that may lead to bleeding or perforation, as assessed by an EGDS performed during screening period.\n- Persistent toxicity related to prior therapy, Grade >1 according to NCI CTCAE Version 5.0\n- Uncontrolled tumour-related pain. Patients requiring narcotic pain medication must be on a stable regimen at study entry\n- Uncontrolled pleural effusion, pericardial effusion or ascites requiring repeated drainage more than once every 28 days. Indwelling drainage catheters are allowed\n- Unstable angina\n- Myocardial infarction within 6 months before enrolment"}

Primary endpoints

• {"endpoint_text":"- Safety and tolerability: Incidence of DLTs (Main Study/Dose Escalation only only)\n- Safety and tolerability: Incidence of Treatment Emergent Adverse Events (TEAEs) occurring while patients are on treatment or up to 30 days after the last dose of last study treatment\n- Safety and tolerability: Incidence of Serious Adverse Events (SAEs) occurring while patients are on treatment or up to 90 days after the last dose of last study treatment or to a minimum of 30 days after the last IMP intake in case of initiation of new anti-cancer therapy, whichever occurs first\n- Safety and tolerability: Changes in clinical laboratory parameters, vital signs, ECOG performance status, ECG and physical examination\n- Efficacy: DCR, defined as the proportion of patients who have achieved CR, PR, or stable disease (SD)\n- Efficacy: ORR, defined as the proportion of patients who have achieved CR or PR","definition_or_measurement_approach":"- Incidence of DLTs: assessed during Dose Escalation (Main Study) per protocol-defined DLT criteria (Dose Escalation part only).\n- Incidence of TEAEs: recorded while patients are on treatment or up to 30 days after last study treatment; events graded per NCI CTCAE v5.0.\n- Incidence of SAEs: recorded while on treatment and up to 90 days after last study treatment or minimum 30 days after last IMP intake if new anticancer therapy initiated; recorded per standard SAE reporting.\n- Changes in clinical laboratory parameters, vital signs, ECOG, ECG and physical examination: serial assessments and laboratory tests as per schedule of assessments.\n- DCR: measured as proportion of patients achieving CR, PR, or SD by RECIST v1.1.\n- ORR: measured as proportion of patients achieving CR or PR by RECIST v1.1."}

Secondary endpoints

• {"endpoint_text":"- Exploratory: PD-L1 expression by CPS (Main Study/Expansion)\n- Exploratory: Change in biomarkers in blood and tumour samples\n- Exploratory: Change in blood and tumour-infiltrating immune cells\n- Efficacy: DOR, defined as the time from first documentation of response (CR or PR) until the time of first documentation of disease progression\n- Efficacy: PFS, defined as the time from the first dose of study drugs to the earlier date of assessment of progression, or death by any cause in the absence of progression\n- Efficacy: PFSR, defined as the proportion of patients alive and free of disease progression at specific timepoints\n- Efficacy: OS, defined as the time from the first dose of study drugs to the date of death by any cause","definition_or_measurement_approach":"- PD-L1 CPS: measured by PD-L1 Combined Positive Score on tumour tissue as specified in protocol.\n- Change in biomarkers: serial blood and tumour sample biomarker assays per protocol-specified panels and assays.\n- Change in immune cells: analysis of blood and tumour-infiltrating immune cell populations using protocol-specified assays.\n- DOR: time from first documentation of CR/PR until documented progression by RECIST v1.1.\n- PFS: time from first dose to documented progression or death.\n- PFSR: proportion alive and progression-free at protocol-defined timepoints.\n- OS: time from first dose to death from any cause."}

Italy

Earliest CTIS Part Ii Submission Date

13-06-2024

Latest Decision Or Authorization Date

13-03-2026

Processing Time Days

638

Number Of Sites

3

Number Of Participants

55

Primary sponsor

Full Name

Rottapharm Biotech S.r.l.

Organisation Type

Pharmaceutical company

Country Of Registered Address

Italy

Contract research organisations

Name

Opis S.r.l.

Responsibilities

Operational sponsor duties including monitoring/clinical study activities and drug safety (codes reported: 1,10,12,15 (Drug Safety),6,7) per CTIS record

Third parties

• {"country":"Italy","full_name":"Opis S.r.l.","duties_or_roles":"Codes: 1, 10, 12, 15 (Drug Safety), 6, 7","organisation_type":"Pharmaceutical company"}