E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patients with histologically diagnosed epithelial ovarian, fallopian tube or primary peritoneal cancer with radiologically or histologically confirmation of relapsed disease, and with known BRCA wildtype. Platinum combination therapy must be an option. |
|
E.1.1.1 | Medical condition in easily understood language |
Patients with relapsed ovarian cancer where platinum combination therapy is an option |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10066697 |
E.1.2 | Term | Ovarian cancer recurrent |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10016180 |
E.1.2 | Term | Fallopian tube cancer |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10080244 |
E.1.2 | Term | Peritoneal cancer index |
E.1.2 | System Organ Class | 10022891 - Investigations |
|
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate the preliminary efficacy of APX005M-carboplatin-PLD and APX005M-radiotherapycarboplatin-PLD combinations by Overall Response Rate (ORR) at 12 weeks |
|
E.2.2 | Secondary objectives of the trial |
- To evaluate Patient Reported Outcomes (PROs) in treatment arms - To evaluate safety by Overall Response Rate (ORR) at 24 weeks, Progression-free survival (PFS) in each treatment arm at 24 months and Disease Control Rate (DCR) at 12 weeks and 24 weeks
Exploratory translational research objectives: - To describe genetic, molecular, and immunological mechanisms in blood and tumor - To explore the efficacy of APX005M in combination in the molecular and immunological subgroups |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Have signed an Institutional Review Board/Independent Ethics Committee-approved informed consent form prior to any study-specific evaluation. 2. Histologically diagnosed epithelial ovarian, fallopian tube or primary peritoneal cancer. 3. Radiological or histological confirmation of relapse disease ≥ 6 month after last chemotherapy 4. Known BRCAwt 5. Have completed at least one line of platinum-containing chemotherapy (maximum three previous lines of therapy are permitted). Earlier PARPi and earlier bevacizumab therapies are permitted 6. Must have measurable or evaluable disease according to RESIST 1.1. 7. Baseline biopsy: Tissue biopsy for submission to central laboratory prior to study treatment should be from a newly obtained metastatic biopsy, if there is a lesion suitable for biopsy and the subject consents to this procedure. If a metastatic biopsy is not feasible, or patient is unwilling to provide new biopsy, archival tissue samples should be submitted. Archival tissue sample from metastatic site is preferred; however, archival tissue sample of primary tumor is acceptable. 8. Must consent to undergo mandatory tumor biopsy of at least one metastatic site at day 84 (±7). Biopsy at day 84 (±7) is only applicable if surgery is not performed. 9. Age ≥ 18 years 10. Body weight > 30 kg 11. Eastern Cooperative Oncology Group (ECOG) performance status 0-1 12. Must have a life expectancy ≥ 12 weeks. 13. Must have normal Left Ventricular Ejection Fraction (LVEF > 50%) measured by MUGA scan or echocardiography. 14. Must have normal organ and bone marrow function measured within 28 days prior to administration of study treatment as defined below (5% deviation for hematological parameters and 10% deviation for biochemistry is permitted): a. Haemoglobin ≥ 10.0 g/dL (≥ 6.2 mmol/L) with no blood transfusion in the past 28 days b. Absolute neutrophil count (ANC) ≥ 1.5 x 109/L c. Platelet count ≥ 100 x 109/L d. Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN) e. Aspartate aminotransferase (AST) (Serum Glutamic Oxaloacetic Transaminase (SGOT)) /Alanine aminotransferase (ALT) (Serum Glutamic Pyruvate Transaminase (SGPT)) ≤ 2.5 x institutional upper limit of normal unless liver metastases are present in which case, they must be ≤ 5 x ULN 15. Must have creatinine clearance estimated ≥ 50 mL/min using the Cockcroft-Gault formula 16. A participant is eligible to participate, if she is not pregnant or breastfeeding, and at least 1 of the following conditions applies: - Is not a woman of childbearing potential (WOCBP) OR - Is a WOCBP and using a contraceptive method that is highly effective (with a failure rate of < 1% per year), with low user dependency, or be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long-term and persistent basis), as described in the intervention period and for at least 90 days after the last dose of APX005M and agrees not to donate eggs (ova, oocytes) to others or freeze/store for her own use for the purpose of reproduction during this period. The investigator should evaluate the potential for contraceptive method failure (i.e., noncompliance, recently initiated) prior to the first dose of study intervention.
- A WOCBP must have a negative urine or serum pregnancy test within 28 days of study treatment and a confirmed negative highly sensitive pregnancy test within 24 hours before the first dose of study intervention |
|
E.4 | Principal exclusion criteria |
1)Previous immunotherapy (for example anti-PD-1/L1).2)Other malignancy unless curatively treated with no evidence of disease for ≥ 3years, except adequately treated non-melanoma skin cancer, curatively treated in situ cancer of the cervix, ductal carcinoma in situ (DCIS) and stage 1 grade 1 endometrial carcinoma.3)Resting ECG indicating uncontrolled, potentially reversible cardiac conditions, as judged by the investigator (e.g. unstable ischemia, uncontrolled symptomatic arrhythmia, congestive heart failure, QTcF prolongation >500 ms, electrolyte disturbances, etc.), or subjects with congenital long QT syndrome.4)Subjects with myelodysplastic syndrome/acute myeloid leukemia or with features suggestive of MDS/AML.5) Subjects with symptomatic uncontrolled brain metastases. A scan to confirm the absence of brain metastases is not required. Subjects with spinal cord compression unless considered to have received definitive treatment for this and evidence of clinically stable disease for 28 days.6)Subjects with a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of randomization. Subjects who have received acute, low-dose, systemic immunosuppressant medications (e.g., a one-time dose of dexamethasone for nausea) or physiologic replacement doses (i.e. prednisone 5 - 7.5 mg/day) for adrenal insufficiency may be enrolled in the study. Inhaled or topical steroids, and adrenal replacement steroid doses ≤ 10 mg daily prednisone equivalent, are permitted in the absence of active autoimmune disease.7)Prior radiation therapy.8)Planned concomitant therapy with any other anticancer therapy.9)Conditions requiring ongoing therapy with antibiotics.10)History of any arterial thromboembolic event within 3 months prior to first dose of APX005M.11)Active coagulopathy.12)Previous allogeneic bone marrow transplant or double umbilical cord blood transplantation.13)History of organ transplant.14)Major surgery or significant traumatic injury within 4 weeks prior to first dose of study drugs.15)Pregnant or breastfeeding women.16)Subjects with a known hypersensitivity to any of the excipients of the product.17)Any unresolved toxicity NCI CTCAE Grade ≥ 2 from previous anticancer therapy, except alopecia, vitiligo, and the laboratory values defined in the inclusion criteria:a.Subjects with Grade ≥ 2 neuropathy will be evaluated on a case-by-case basis after consultation with the Lead Principal Investigator (PI) of the respective collaborative group.b.Subjects with irreversible toxicity not reasonably expected to be exacerbated by treatment with study drugs may be included only after consultation with the Lead PI of the respective collaborative group.18)Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease [e.g., colitis or Crohn's disease], diverticulitis [with the exception of diverticulosis], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome [granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc]). The following are exceptions to this criterion:a.Subjects with vitiligo or alopecia.b.Subjects with hypothyroidism (e.g. following Hashimoto syndrome) stable on hormone replacement.c.Any chronic skin condition that does not require systemic therapy.d.Subjects without active disease in the last 5 years may be included, but only after consultation with the Lead PI of the respective collaborative group.e.Subjects with celiac disease controlled by diet alone.19)Subjects considered a poor medical risk due to a serious, uncontrolled medical disorder, non-malignant systemic disease or active, uncontrolled infection. Examples include, but are not limited to, uncontrolled symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, recent (within 3 months), uncontrolled major seizure disorder, serious chronic gastrointestinal conditions associated with diarrhea, interstitial lung disease or any psychiatric disorder/social situations that would limit compliance with study requirement, substantially increase risk of incurring AEs or compromise the ability of the Subject to give written informed consent.20)Immunocompromised subjects, e.g. subjects who are known to be serologically positive for human immunodeficiency virus (HIV).21)Active infection including tuberculosis, hepatitis B (known positive HBV surface antigen (HBsAg)), hepatitis C. Subjects with a past or resolved HBV infection are eligible. Subjects positive for hepatitis C (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA.22)Receipt of live attenuated vaccine within 30 days prior to the first dose of Investigational Product (IP). Note: COVID-19 vaccination must be performed minimum 7 days prior to first dose of APX005M. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Overall Response Rate (ORR) at 12 weeks |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
1. ORR at 24 weeks 2. Progression-free survival (PFS) at 24 months 3. Safety until 30 days after last dose of study drug(s) 4. PROs at baseline and every 12 weeks for 24 months 5. Disease Control Rate (DCR) at 12 weeks and 24 weeks
Exploratory translational research endpoints 6. Evaluation of changes in molecular and immunological markers of response and/or resistance over time 7. Correlation between changes in molecular and immunological markers and efficacy and/or resistance to treatment in defined subgroups |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. 24 weeks 2. 24 months 3. 30 days after last dose 4. 24 months 5. 12 weeks and 24 weeks 6. 24 weeks 7. 24 weeks |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
Radiotherapy-carboplatin-PLD |
|
E.8.2.4 | Number of treatment arms in the trial | 3 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 11 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Belgium |
Czechia |
Denmark |
Finland |
Norway |
Switzerland |
|
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 3 |