Ovarian CancerPhase 2APX005MNCT05201001
APX005M in Patients With Recurrent Ovarian Cancer
A Phase 2 study testing APX005M in people with Ovarian Cancer, run by Nordic Society of Gynaecological Oncology - Clinical Trials Unit at 1 site in Denmark.
Trial summary
The overall objective is to demonstrate preliminary efficacy of APX005M-carboplatin-PLD and APX005M-radiotherapy-carboplatin-PLD combinations as treatment for relapsed BRCAwt ovarian cancer patients, where platinum combination therapy is an option. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Ovarian Cancer
- What is being tested?
- APX005M
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteDenmark
- Study dates
- 7 Sep 2023to 7 Sep 2023
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Have signed an Institutional Review Board/Independent Ethics Committee-approved informed consent form prior to any study-specific evaluation.
- Histologically diagnosed epithelial ovarian, fallopian tube or primary peritoneal cancer.
- Radiological or histological confirmation of relapse disease ≥ 6 month after last chemotherapy
- Known BRCAwt
- Have completed at least one line of platinum-containing chemotherapy (maximum three previous lines of therapy are permitted). Earlier PARPi treatment permitted
- Must have measurable or evaluable disease according to RESIST 1.1.
- 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. 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.
- Must consent to undergo mandatory tumor biopsy of at least one metastatic site at baseline and at day 84 ( 7). Biopsy at day 84 ( 7) is only applicable if surgery is not performed. -
Who cannot join
- Previous immunotherapy (for example anti-PD-1/L1).
- 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.
- 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.
- Subjects with myelodysplastic syndrome/acute myeloid leukemia or with features suggestive of MDS/AML. Page 48 af 128 ENGOT-OV64/NSGO-CTU-SOLERO EudraCT: 2020-005990-29 Final Version 1.0, 06. July 2021
- 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.
- 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.
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- Prior radiation therapy.
- Planned concomitant therapy with any other anticancer therapy
- Conditions requiring ongoing therapy with antibiotics
- History of any arterial thromboembolic event within 3 months prior to first dose of APX005M
- Active coagulopathy
- Previous allogeneic bone marrow transplant or double umbilical cord blood transplantation
- History of organ transplant
- Major surgery or significant traumatic injury within 4 weeks prior to first dose of study drugs
- Pregnant or breastfeeding women.
- Subjects with a known hypersensitivity to any of the excipients of the product.
- Any unresolved toxicity NCI CTCAE Grade ≥ 2 from previous anticancer therapy, except alopecia, vitiligo, and the laboratory values defined in the inclusion criteria
- 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
- 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.
- 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:
- Subjects with vitiligo or alopecia
- Subjects with hypothyroidism (e.g. following Hashimoto syndrome) stable on hormone replacement Page 49 af 128 ENGOT-OV64/NSGO-CTU-SOLERO EudraCT: 2020-005990-29 Final Version 1.0, 06. July 2021
- Any chronic skin condition that does not require systemic therapy
- 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.
- Subjects with celiac disease controlled by diet alone
- 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.
- Immunocompromised subjects, e.g. subjects who are known to be serologically positive for human immunodeficiency virus (HIV).
- Active infection including tuberculosis (clinical evaluation that includes clinical history, physical examination and radiographic findings, and TB testing in line with local practice), hepatitis B (known positive HBV surface antigen (HBsAg)), hepatitis C.
- Subjects with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody [anti-HBc] and absence of HBsAg) are eligible. Subjects positive for hepatitis C (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA.
- Receipt of live attenuated vaccine within 30 days prior to the first dose of Investigational Product (IP). Note: Subjects, if enrolled, should not receive live vaccine whilst receiving IP and up to 30 days after the last dose of IP. COVID-19 vaccination must be performed minimum 7 days prior to first dose of APX005M. -
Trial locations and contacts
1 site in 1 country.
About this study
Official title: An Early Phase Randomized Trial of APX005M in BRCAwt Patients With Recurrent Ovarian Cancer
The overall objective is to demonstrate preliminary efficacy of APX005M-carboplatin-PLD and APX005M-radiotherapy-carboplatin-PLD combinations as treatment for relapsed BRCAwt ovarian cancer patients, where platinum combination therapy is an option.
Read the detailed description
The rationale for integrating immunotherapy with chemotherapy is based on preclinical studies, which have shown, that chemotherapy induces immunogenic cell death leading to increased recognition of the tumor by the immune system. Carboplatin is shown to inhibit PD-L2 expression, thereby limiting immunosuppression by both dendritic cells and tumor cells. Paclitaxel decreases the percentage of CD4+ and FoxP3+ regulatory T cells (Tregs) and reduces their cytokine production without disrupting the function of its effector counterpart (CD4+ and FoxP3 effector T (Teff) cells). Several trials have shown effect of checkpoint inhibition following chemotherapy and radiotherapy, most notably in the PACIFIC trial in stage III NSCLC [63]. We therefore hypothesize, that the proposed combined therapies will yield improved clinical effect in this patient population.
The hypotheses in this study is, that the CD-40 agonist APX005M with or without radiotherapy, and in combination with platinum-doublet chemotherapy, will provide the necessary immune activation and serve as a basis for increased clinical effect of the combination.
- Conditions
- Ovarian Cancer
- Being tested
- APX005M
- Keywords
- ovarian cancer, immunotherapy
- Medical subject headings
- Ovarian Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
APX005MDrug
Also called Radiation therapy, carboplatin and PLD
adding immunotherapy with or without radiation therapy to chemotherapy. Low dose radiation therapy is to sensitise tumour cells to immunotherapy.
| Study group | Role | What they receive |
|---|---|---|
| Standard of Care | Active comparator | Carboplatin AUC = 5, IV day 1 and pegylated liposomal doxorubicin (PLD) 30 mg/m , IV day1 q4 wks
Total:6 cycles or until progressive disease or unacceptable toxicity. Receives: Drug: APX005M |
| APX005M | Experimental | Carboplatin AUC = 5, IV day 1 combined with pegylated liposomal doxorubicin (PLD) 30 mg/m , IV day1 q4 wks APX005M 0.3 mg/kg, days 1 \& 15 IV q4 wks x concomitant with chemotherapy
Total:6 cycles or until progressive disease or unacceptable toxicity. Receives: Drug: APX005M |
| APX005M+RT | Experimental | Carboplatin AUC = 5, IV day 1 combined with pegylated liposomal doxorubicin (PLD) 30 mg/m , IV day1 q4 wks APX005M 0.3 mg/kg, days 1 \& 15 IV q4 wks x concomitant with chemotherapy External beam radiation therapy; a dose of 0.5 Gy per fraction, administered as single fractions prior to APX005M administration; days 1 \& 15 q4 wks x 6 cycles. Maximum 24 wks of therapy; total dose 6 Gy.
Total:6 cycles or until progressive disease or unacceptable toxicity. Receives: Drug: APX005M |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall Response Rate according to RECIST at 12 weeks of treatment
To evaluate the preliminary efficacy of APX005M-carboplatin-PLD and APX005M radiotherapycarboplatin-PLD combinations
Measured: 18 months
Secondary outcomes (1)
Adverse events
To evaluate adverse events, safety \& feasibility of the two combinations
Measured: 18 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Jan 2022
- Study start7 Sep 2023
- Primary completion7 Sep 2023
- Study completion7 Sep 2023
Why it stopped: IMP provider company (Apexigen) is sold, thus both IMP and grant is terminated
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Ovarian CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- randomised, open-label, three arm study
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Nordic Society of Gynaecological Oncology - Clinical Trials Unit
- Sponsor type
- University, hospital or other
- Collaborators
- Belgian Gynaecological Oncology Group, GSO Global Clinical Research BV, The Central and Eastern European Gynecologic Oncology Group, Swiss GO Trial Group
- Responsible party
- Sponsor
- Investigators
- Mansoor R Mirza, Study chair, NSGO-CTU
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05201001
- Sponsor's protocol ID
- ENGOT-OV64/NSGO-CTU-SOLERO
- Acronym
- APX005M
- Status last verified
- Apr 2022
- First submitted
- 9 Jul 2021
- Last updated
- 11 Sep 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided: NSGO-CTU can be contacted
Study at a glance
From the registry record, last updated by the sponsor on 11 Sep 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Early Phase Randomized Trial of APX005M in BRCAwt Patients With Recurrent Ovarian Cancer
- ClinicalTrials.gov ID
- NCT05201001
- Acronym / sponsor ID
- APX005M / ENGOT-OV64/NSGO-CTU-SOLERO
- Conditions
- Ovarian Cancer
- Keywords
- ovarian cancer, immunotherapy
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: IMP provider company (Apexigen) is sold, thus both IMP and grant is terminated
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Nordic Society of Gynaecological Oncology - Clinical Trials UnitUniversity, hospital or other
- Collaborators
- Belgian Gynaecological Oncology Group, GSO Global Clinical Research BV, The Central and Eastern European Gynecologic Oncology Group, Swiss GO Trial Group
- Study start
- 7 Sep 2023 (actual)
- Primary completion
- 7 Sep 2023 (actual)
- Study completion
- 7 Sep 2023 (actual)
- First posted
- 21 Jan 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The overall objective is to demonstrate preliminary efficacy of APX005M-carboplatin-PLD and APX005M-radiotherapy-carboplatin-PLD combinations as treatment for relapsed BRCAwt ovarian cancer patients, where platinum combination therapy is an option.
Detailed description
The rationale for integrating immunotherapy with chemotherapy is based on preclinical studies, which have shown, that chemotherapy induces immunogenic cell death leading to increased recognition of the tumor by the immune system. Carboplatin is shown to inhibit PD-L2 expression, thereby limiting immunosuppression by both dendritic cells and tumor cells. Paclitaxel decreases the percentage of CD4+ and FoxP3+ regulatory T cells (Tregs) and reduces their cytokine production without disrupting the function of its effector counterpart (CD4+ and FoxP3 effector T (Teff) cells). Several trials have shown effect of checkpoint inhibition following chemotherapy and radiotherapy, most notably in the PACIFIC trial in stage III NSCLC [63]. We therefore hypothesize, that the proposed combined therapies will yield improved clinical effect in this patient population.
The hypotheses in this study is, that the CD-40 agonist APX005M with or without radiotherapy, and in combination with platinum-doublet chemotherapy, will provide the necessary immune activation and serve as a basis for increased clinical effect of the combination.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
- Model description
- randomised, open-label, three arm study
| Arm | Type | Receives |
|---|---|---|
| Standard of Care | Active comparator | Drug: APX005MCarboplatin AUC = 5, IV day 1 and pegylated liposomal doxorubicin (PLD) 30 mg/m , IV day1 q4 wks Total:6 cycles or until progressive disease or unacceptable toxicity. |
| APX005M | Experimental | Drug: APX005MCarboplatin AUC = 5, IV day 1 combined with pegylated liposomal doxorubicin (PLD) 30 mg/m , IV day1 q4 wks APX005M 0.3 mg/kg, days 1 \& 15 IV q4 wks x concomitant with chemotherapy Total:6 cycles or until progressive disease or unacceptable toxicity. |
| APX005M+RT | Experimental | Drug: APX005MCarboplatin AUC = 5, IV day 1 combined with pegylated liposomal doxorubicin (PLD) 30 mg/m , IV day1 q4 wks APX005M 0.3 mg/kg, days 1 \& 15 IV q4 wks x concomitant with chemotherapy External beam radiation therapy; a dose of 0.5 Gy per fraction, administered as single fractions prior to APX005M administration; days 1 \& 15 q4 wks x 6 cycles. Maximum 24 wks of therapy; total dose 6 Gy. Total:6 cycles or until progressive disease or unacceptable toxicity. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Have signed an Institutional Review Board/Independent Ethics Committee-approved informed consent form prior to any study-specific evaluation.
- Histologically diagnosed epithelial ovarian, fallopian tube or primary peritoneal cancer.
- Radiological or histological confirmation of relapse disease ≥ 6 month after last chemotherapy
- Known BRCAwt
- Have completed at least one line of platinum-containing chemotherapy (maximum three previous lines of therapy are permitted). Earlier PARPi treatment permitted
Key exclusion criteria (30 listed)
- Previous immunotherapy (for example anti-PD-1/L1).
- 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.
- 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.
- Subjects with myelodysplastic syndrome/acute myeloid leukemia or with features suggestive of MDS/AML. Page 48 af 128 ENGOT-OV64/NSGO-CTU-SOLERO EudraCT: 2020-005990-29 Final Version 1.0, 06. July 2021
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| APX005MAlso: Radiation therapy, carboplatin and PLDadding immunotherapy with or without radiation therapy to chemotherapy. Low dose radiation therapy is to sensitise tumour cells to immunotherapy. | Drug | APX005M, APX005M+RT, Standard of Care |
Primary outcome
Overall Response Rate according to RECIST at 12 weeks of treatment
Time frame: 18 months
To evaluate the preliminary efficacy of APX005M-carboplatin-PLD and APX005M radiotherapycarboplatin-PLD combinations
1 secondary outcome
Adverse events
Time frame: 18 months
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Sep 2023.
- Individual participant dataSharing planned: Undecided. NSGO-CTU can be contacted
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Mansoor R Mirza study chair
NSGO-CTU
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing APX005M in people with Ovarian Cancer, run by Nordic Society of Gynaecological Oncology - Clinical Trials Unit at 1 site in Denmark.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 30 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 11 Sep 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Denmark. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Overall Response Rate according to RECIST at 12 weeks of treatment (time frame: 18 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Sep 2023.