Advanced colorectal, esophageal, gastric, and ovarian cancers Cancer late-stage cancer
Conditions
Interventions
None listed
Sponsors
Immunocore Limited
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: 1. Participant must be >=18 years of age, inclusive, at the time of signing the ICF 2. ECOG status of 0 or 1 at start of treatment. 3. HLA-A*02:01-positive (testing at central laboratory). 4. PIWIL1 expression in >=10% of tumor cells must be established in patient specimen 5. Histologically confirmed advanced (i.e., either locally advanced or metastatic disease that is unresectable) colorectal, esophageal, gastric, or ovarian carcinoma. 6. Participants must meet tumor PIWIL1 testing requirements: a. ALL COHORTS: An archival or newly collected tumor biopsy must be sent to the study central laboratory. An archival biopsy may be provided as an FFPE tissue block, or an FFPE pre-cut slide. b. MONOTHERAPY COHORTS: a tumor biopsy sample must be sent to the study central laboratory and a positive result must be received prior to enrolling. If data indicate that clinical activity is restricted to participants with higher tumor PIWIL1 expression, subsequent enrollment may be restricted to participants whose tumors are confirmed as having higher PIWIL1 expression; details will be documented in the SPM. c. COMBINATION COHORTS: An archival or newly collected tumor biopsy must be confirmed as adequate (as defined in the study Laboratory Manual) locally prior to completion of Screening and subsequently sent to the study central laboratory. If data indicate that clinical activity is restricted to participants with higher tumor PIWIL1 expression, subsequent enrollment may be restricted to participants whose tumors are confirmed as having higher PIWIL1 expression; details will be documented in the SPM. 7. Participants must meet RECIST v1.1 criteria for evaluable/measurable disease based on investigator assessment: a. In dose-escalation, regimen optimization, and Phase 2, participants must have evaluable disease (at least 1 non-target or target lesion), b. In expansion, all participants must have at least 1 target lesion. c. Tumors in irradiated areas are acceptable only if there is subsequent documented radiographic progression 8. Participants must meet the histology, biomarker, and prior treatment requirements specified in Table 9 of the lmmunocore study protocol for the applicable arm and study part. Required therapies must have been given for unresectable/metastatic disease or in the neoadjuvant or adjuvant setting with disease progression during or within 6 months of completing neoadjuvant or adjuvant therapy. 9. Male and female participants of childbearing potential who are sexually active with a non¬ sterilized partner must agree to use highly effective methods of birth control from the study screening date until 6 months after the final dose of the study treatment; cessation of birth control after this point shall be discussed with a responsible physician. Highly effective methods of contraception are described in Section 10.5 of the lmmunocore study protocol. a. Pregnant or lactating women are prohibited from enrolling in this study. b. Male participants are not allowed to donate sperm from the time of enrollment until 6 months post-administration of study treatments. 10. Capable of giving signed informed consent as described in Section 10.1.3 of the lmmunocore study protocol, which includes compliance with the requirements and restrictio
Exclusion criteria
Exclusion criteria: 1. Presence of untreated or symptomatic CNS metastases, leptomeningeal disease, or cord compression. NOTE: Participants with treated CNS lesions may enroll provided all the following apply: a. Treated CNS lesions must be radiographically stable for >=2 weeks after intervention (surgery and/or radiation). b. Participants must be neurologically stable off systemic corticosteroids for at least 2 weeks prior to enrollment. 2. Bowel obstruction within 3 months prior to the planned first dose of study treatment 3. Participants at high risk for vital organ perforation, fistula formation, or hemorrhage, defined as: a. History of gastrointestinal perforation, abdominal fistula, intra-abdominal abscess, or active gastrointestinal bleeding within 6 months of the first dose of study treatment OR b. Single tumor lesion with diameter > 100 mm, tumor adjacent to or directly involving the surface of a vital organ (e.g., serosal surface of the bowel, airway, or major vessel), AND treatment with an anti-angiogenic agent within 3 months of the first dose of study treatment 4. Ongoing ascites or effusion requiring recurrent drainage (i.e, at least twice within 28 days prior to the planned first dose of study treatment). NOTE: Participants with an indwelling catheter in place for at least 14 days prior to the planned first dose of study treatment may be eligible following discussion with the study medical monitor. a. For combination with bevacizumab, any ascites or effusion requiring drainage within 28 days prior to the first dose of study treatment is exclusionary 5. Participants with presence of NCI CTCAE >=Grade 2 toxicity due to prior cancer therapy, with the following exceptions: a. Participants with Grade 2 alopecia, Grade 2 endocrine disorder (on stable replacement doses and asymptomatic), Grade 2 hypophosphatemia (on appropriate replacement therapy), Grade 2 ototoxicity, or Grade 2 peripheral neuropathy may enroll in any arm. b. Participants with other stable Grade 2 toxicities due to prior anticancer therapy, that are anticipated to have minimal risk of worsening due to treatment with IMC-R117C and applicable combination partner(s), may enroll only with prior written approval from the study medical monitor. 6. Hypersensitivity to: a. IMC-R117C or any associated excipients (all arms), b. Bevacizumab, Chinese Hamster Ovary cell products, other recombinant human or humanized antibodies, 5-FU, capecitabine, or any associated excipients (Arm Band Arm D) c. Cetuximab, encorafenib, or any associated excipients (Arm C) 7. Receipt of anticancer therapy for the disease under study within the following times prior to the first planned dose of study treatment (NOTE: washout periods do not apply to therapies that will be continued as combination partners. For maintenance arms, washout periods do not apply to therapies given for induction): a. Cellular therapies (e.g., T-cell therapies): 90 days. NOTE: The investigator must discuss any prior cellular therapy treatment with the medical monitor, provide evidence (if possible) confirming that no residual biological/immunological activity remains, discuss any associated potential risks, and determine whether any additional monitoring is indicated. In addition, the investigator and medical monitor m
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary: Clinical Utility Of PIWIL1 ISH Assay Objective: To evaluate the clinical utility of the PIWIL1 ISH assay for predicting response of patients with Advanced PIWIL1-Positive Cancers within the lmmunocore clinical study Endpoint: Identify the clinical utility based on the ORR for evaluable samples tested using the PIWIL1 ISH assay | — |
Countries
Netherlands
Outcome results
None listed