Pelcitoclax + Cobimetinib for Recurrent Ovarian and Endometrial Cancers

Recruiting at 6 trial locations

Age: 18+

Sex: Female

Trial Phase: Phase 1

Sponsor: National Cancer Institute (NCI)

Must be taking: Platinum-based therapy

Must not be taking: CYP3A4 inhibitors, CYP3A4 inducers

Disqualifiers: Uncontrolled illness, Retinal pathology, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 1

Duration: 28 days per cycle, repeated until disease progression or unacceptable toxicity

42 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a combination treatment for ovarian and endometrial cancers that have returned after initial improvement. Researchers are testing the safety and optimal dosage of two drugs: pelcitoclax (also known as APG-1252), which promotes cancer cell death, and cobimetinib, which blocks signals that cause cancer cells to multiply. The trial aims to determine if these drugs together can shrink or stabilize tumors. Individuals whose ovarian or endometrial cancer has returned after treatment and who have already tried certain therapies might be suitable for this study. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new combination therapy.

Do I need to stop my current medications to join the trial?

The trial requires that you stop taking any medications that are strong inhibitors or inducers of CYP3A4 at least 7 days before starting the trial drugs. If you're on such medications, you'll need to discuss alternatives with your doctor.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that the combination of pelcitoclax (APG-1252) and cobimetinib is still undergoing safety testing in humans. In this early study phase, researchers focus on assessing the treatment's safety and potential side effects. Detailed safety information remains limited at this stage.

Pelcitoclax aims to kill cancer cells by making survival more difficult for them. Cobimetinib blocks signals that promote cancer cell growth. Although these drugs may work together to slow down or shrink tumors, the primary focus is ensuring their safety when combined. As this is an early study phase, establishing safety details remains crucial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Pelcitoclax and Cobimetinib for recurrent ovarian and endometrial cancers because these treatments bring some fresh approaches to the table. Pelcitoclax is a new type of drug that works by targeting and blocking proteins that help cancer cells survive, which is different from the usual chemotherapy methods. Cobimetinib, on the other hand, targets a specific pathway called the MAPK/ERK pathway, which is involved in cell division and growth. This dual approach could potentially enhance the effectiveness of treatment by attacking cancer cells from different angles, offering hope for more effective management of these challenging cancers.

What evidence suggests that this combination therapy might be an effective treatment for recurrent ovarian and endometrial cancers?

Research has shown that combining pelcitoclax and cobimetinib might help shrink or stabilize tumors in patients with recurring ovarian and endometrial cancers. In this trial, participants will receive both pelcitoclax, which blocks proteins that prevent cancer cells from dying, and cobimetinib, which inhibits a protein that signals cancer cells to grow. These drugs may work better together than alone because they target cancer cells in different ways. Early studies suggest this combination could be promising, but further research is needed to confirm its effectiveness. ^{1 2 3 4 5}

Who Is on the Research Team?

Joyce Liu, MD

Principal Investigator

Dana-Farber - Harvard Cancer Center LAO

Are You a Good Fit for This Trial?

This trial is for adults with recurrent ovarian or endometrial cancer who've had platinum-based therapy and, if applicable, specific prior treatments based on their cancer type. They must be able to take oral meds, provide tissue samples if available, use contraception if needed, and have no other health issues that could interfere.

Inclusion Criteria

I have a history or symptoms of heart disease and need a heart function assessment.

My ovarian cancer worsened within 6 months after my last platinum treatment.

My cancer has returned or spread and cannot be surgically removed, with no standard treatments left.

Exclusion Criteria

I am allergic to medications similar to APG-1252 or cobimetinib.

I do not have any unmanaged ongoing illnesses.

I have a stomach or intestine condition that affects how I absorb pills.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive APG-1252 intravenously once a week and cobimetinib orally on days 1-21 of each 28-day cycle. Biopsies, blood collection, CT/MRI scans, and ECHO/MUGA are conducted throughout the trial.

28 days per cycle, repeated until disease progression or unacceptable toxicity

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessment of adverse events and progression-free survival.

Up to 30 days after removal from study therapy

Long-term Follow-up

Exploration of markers of response and resistance, and assessment of radiological response and RAS pathway signaling.

Up to 3 years

What Are the Treatments Tested in This Trial?

Interventions

• APG-1252
• Cobimetinib

Trial Overview The trial tests a combo of two drugs: Pelcitoclax (APG-1252) which may help kill cancer cells by blocking certain proteins, and Cobimetinib which targets abnormal proteins in cancers with a BRAF gene mutation. The goal is to see if this drug duo can shrink or stabilize the tumors.

How Is the Trial Designed?

Group I: Treatment (pelcitoclax, cobimetinib) Experimental Treatment 8 Interventions

Patients receive APG-1252 IV Q7D. Patients also receive cobimetinib PO QD on days 1-21 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo biopsy and collection of blood on study and undergo CT and/or MRI throughout the trial. Patients undergo ECHO or MUGA during screening and on study.

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

Patients with recurrent ovarian cancer are categorized as either platinum-sensitive or platinum-resistant, which influences treatment options; platinum-sensitive patients often benefit from re-treatment with paclitaxel/platinum combinations, while platinum-resistant patients may receive single-agent therapies like altretamine or topotecan.

For platinum-sensitive patients with minimal residual disease, intensive intraperitoneal therapy with cisplatin and paclitaxel shows the most promise for long-term disease-free survival, highlighting the importance of tailored treatment strategies based on disease characteristics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of refractory and recurrent ovarian cancer. Alberts, DS.[2005]

Ovarian cancer (OC) has a high mortality rate and is often diagnosed at advanced stages, particularly type II tumors, which are associated with poor prognosis and resistance to standard treatments like chemotherapy.

Recent advances in molecular biology and the exploration of immunotherapy are promising for improving treatment options for recurrent and refractory OC, highlighting the importance of identifying prognostic and predictive biomarkers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New Achievements from Molecular Biology and Treatment Options for Refractory/Relapsed Ovarian Cancer-A Systematic Review. Bachmann, C.[2023]

In a study of 101 women with recurrent endometrial, cervical, and ovarian cancer treated with immunotherapy, prior antibiotic use (pABX) was linked to a significantly lower response rate, progression-free survival (PFS), and overall survival (OS) compared to those who did not use antibiotics.

Specifically, women who received pABX had a PFS of only 2.9 months and an OS of 9.3 months, while those without antibiotics had a PFS of 8.9 months and an OS of 19.9 months, indicating that prior antibiotic use may negatively impact the effectiveness of immunotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of antibiotic treatment on immunotherapy response in women with recurrent gynecologic cancer. Chambers, LM., Michener, CM., Rose, PG., et al.[2021]

Advanced epithelial ovarian cancer responds well to first-line chemotherapy, with 70-80% of patients showing a response, but most eventually relapse and develop chemoresistant disease.

New treatment options, including topoisomerase I inhibitors and immunotherapy, are being explored for patients with recurrent ovarian cancer, highlighting the need for clinical trials to improve outcomes, especially for those with platinum-resistant disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Salvage chemotherapy for epithelial ovarian carcinoma. Christian, MC., Trimble, EL.[2015]

Atezolizumab, a PD-L1 inhibitor, was well tolerated in patients with advanced ovarian and uterine cancers, with no new safety concerns and mostly mild treatment-related adverse events.

Preliminary results showed anti-tumor activity in some patients, with long durations of response, suggesting that atezolizumab may be a promising treatment option for these cancers, especially in those with high microsatellite instability.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety, clinical activity and biomarker assessments of atezolizumab from a Phase I study in advanced/recurrent ovarian and uterine cancers. Liu, JF., Gordon, M., Veneris, J., et al.[2019]

Pembrolizumab and dostarlimab, immune checkpoint inhibitors, have been approved for treating advanced recurrent endometrial cancer in patients with specific molecular subgroups, particularly those with mismatch repair deficiency (MMRd) or microsatellite instability-high (MSI-H) status, based on data from 15 studies involving 1609 patients.

The combination of pembrolizumab or dostarlimab with lenvatinib has shown efficacy in patients with mismatch repair proficient/microsatellite stable (MMRp/MSS) endometrial cancer, highlighting the importance of biomarker assessment to optimize treatment strategies for different molecular phenotypes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immune Checkpoint Inhibitors Targeting the PD-1/PD-L1 Pathway in Advanced, Recurrent Endometrial Cancer: A Scoping Review with SWOT Analysis. Johnson, RL., Ganesan, S., Thangavelu, A., et al.[2023]

The combination of pembrolizumab and carboplatin was found to be well-tolerated and showed activity in patients with recurrent platinum-resistant ovarian cancer, with a median overall survival of 11.3 months.

Patients with a higher ratio of peripheral CD8+PD1+Ki67+ T cells to tumor burden had significantly longer overall survival, suggesting this ratio could help identify those who may benefit more from this treatment approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab with low-dose carboplatin for recurrent platinum-resistant ovarian, fallopian tube, and primary peritoneal cancer: survival and immune correlates. Liao, JB., Gwin, WR., Urban, RR., et al.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05691504

Testing the Combination of APG-1252 (Pelcitoclax) and ... Giving APG-1252 in combination with cobimetinib may shrink or stabilize tumor in patients with recurrent ovarian and endometrial cancers. Detailed Description.

2. dana-farber.org dana-farber.org/clinical-trials/23-334

A Phase 1 Study of APG-1252 (pelcitoclax) and ... This phase I trial tests the safety, side effects, and best dose of combination therapy with pelcitoclax (APG-1252) and cobimetinib in treating patients ...

3. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2022-11033

Testing the Combination of APG-1252 (Pelcitoclax) and ... Giving APG-1252 in combination with cobimetinib may shrink or stabilize tumor in patients with recurrent ovarian and endometrial cancers. Eligibility Criteria ...

4. trialx.com trialx.com/clinical-trials/listings/266746/testing-the-combination-of-apg-1252-pelcitoclax-and-cobimetinib-in-recurrent-ovarian-and-endometrial-cancers/

Testing the Combination of APG-1252 (Pelcitoclax) and ... Giving APG-1252 in combination with cobimetinib may shrink or stabilize tumor in patients with recurrent ovarian and endometrial cancers.

5. go.drugbank.com go.drugbank.com/drugs/DB05239/clinical_trials?conditions=DBCOND0021883%2CDBCOND0131677&phase=1&purpose=treatment&status=recruiting

Cobimetinib Recruiting Phase 1 Trials for Recurrent ... Testing the Combination of APG-1252 (Pelcitoclax) and Cobimetinib in Recurrent Ovarian and Endometrial Cancers. Cobimetinib (DB05239) · Pelcitoclax (DB16285) ...