Cabozantinib + Pamiparib for Advanced Cancer

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: M.D. Anderson Cancer Center

Must not be taking: CYP3A inhibitors, Herbal medications

Disqualifiers: Uncontrolled hypertension, Recent stroke, others

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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 6 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine the optimal dose and side effects of two drugs, cabozantinib (Cabometyx) and pamiparib (BGB-290), for treating advanced solid tumors that have spread or do not respond to standard treatments. These drugs may inhibit tumor growth by blocking specific enzymes that aid cancer cell proliferation. Suitable candidates for this trial have advanced solid tumors unresponsive to standard treatments or possess a specific genetic marker, such as a BRCA mutation. As a Phase 1 trial, the research focuses on understanding the treatment's effects in people, offering participants the chance to be among the first to receive this potentially groundbreaking therapy.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications. However, you cannot take certain drugs that affect liver enzymes (CYP3A inhibitors or inducers) or herbal supplements during the study. It's best to discuss your current medications with the study team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that the combination of cabozantinib and pamiparib is generally well-tolerated by patients with advanced solid tumors. Early results indicate that pamiparib is safe, particularly for those with advanced solid and ovarian cancers. Cabozantinib has reduced disease progression or death by 40% in some cases.

One study found that taking pamiparib twice a day and cabozantinib once a day was manageable for patients, with only mild side effects reported. This suggests the treatment might be safe for most people. However, as this is an early-stage trial, not all side effects may be known yet. Discuss potential risks with the clinical trial team and consider them alongside the benefits. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about cabozantinib and pamiparib for advanced cancer because these drugs work differently from most standard treatments. Cabozantinib is a tyrosine kinase inhibitor that targets multiple pathways involved in tumor growth and spread, offering a broad approach against cancer cells. Pamiparib is a PARP inhibitor, which helps prevent cancer cells from repairing themselves, making them more vulnerable to treatment. Together, this combination has the potential to attack cancer from different angles, possibly leading to better outcomes than current therapies that typically focus on just one pathway.

What evidence suggests that cabozantinib and pamiparib might be effective for advanced cancer?

Research has shown that cabozantinib can help treat advanced solid tumors. Specifically, studies found that 22% of patients who used cabozantinib after other treatments experienced tumor shrinkage or disappearance. On average, these patients lived about 17.4 months after starting treatment. Pamiparib, another cancer treatment, blocks certain enzymes that cancer cells need to grow. This trial will evaluate the combination of cabozantinib and pamiparib to determine their combined effectiveness in treating advanced cancers. Although there are promising signs, more research is needed to assess how well cabozantinib and pamiparib work together in this context. ^{1 3 6 7 8}

Who Is on the Research Team?

Siqing FU, MD

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

Adults with advanced solid tumors that are resistant to standard treatments or have no standard treatment options available. Participants must have specific genetic markers related to tumor growth, be able to take oral medication, and not have had certain recent treatments. They should also meet various health criteria like adequate blood cell counts and organ function, agree to use effective contraception, and not be pregnant or breastfeeding.

Inclusion Criteria

My condition has a specific genetic feature confirmed by a certified lab.

I can take pills and do not have chronic stomach or absorption problems.

I am fully active or restricted in physically strenuous activity but can do light work.

Exclusion Criteria

Pregnancy or breastfeeding

I have not received a live vaccine recently.

I am currently taking blood thinners.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive cabozantinib orally once daily and pamiparib orally twice daily. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Up to 6 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

What Are the Treatments Tested in This Trial?

Interventions

• Cabozantinib
• Pamiparib

Trial Overview The trial is testing the combination of two drugs, Cabozantinib and Pamiparib, for their effectiveness in stopping tumor growth by inhibiting enzymes needed for cell proliferation. It aims to determine the optimal dosages and document any side effects when used together on patients with refractory advanced solid tumors.

How Is the Trial Designed?

Group I: Treatment (cabozantinib, pamiparib) Experimental Treatment 2 Interventions

Patients receive cabozantinib PO QD and pamiparib PO BID. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Cabozantinib is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Cabometyx for:

• Renal cell carcinoma
• Hepatocellular carcinoma

Approved in United States as Cabometyx for:

• Renal cell carcinoma
• Hepatocellular carcinoma

Approved in Canada as Cabometyx for:

• Renal cell carcinoma
• Hepatocellular carcinoma

Approved in Japan as Cabometyx for:

• Renal cell carcinoma

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

Published Research Related to This Trial

Pamiparib demonstrated promising efficacy in treating locally advanced or metastatic HER2-negative breast cancer with deleterious or suspected deleterious BRCA1/2 mutations, achieving an objective response rate of 38.2% in triple-negative breast cancer and 61.9% in hormone receptor-positive cohorts.

The treatment was generally well-tolerated, although hematologic adverse events were common, leading to dose reductions in 64.8% of patients, indicating a need for monitoring but an overall acceptable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pamiparib in patients with locally advanced or metastatic HER2-negative breast cancer with germline BRCA mutations: a phase II study. Xu, B., Sun, T., Shi, Y., et al.[2023]

In a study involving 180 patients with advanced solid tumors, the combination of pamiparib and tislelizumab demonstrated an overall objective response rate (ORR) of 20%, with the highest response (47.4%) observed in patients with triple-negative breast cancer (TNBC) who had BRCA1/2 mutations or homologous recombination deficiency.

While the treatment showed promising antitumor activity, it was associated with a significant incidence of treatment-emergent adverse events, with 61.7% of patients experiencing grade 3 or higher side effects, indicating that while the therapy is effective, careful monitoring for safety is necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pamiparib in combination with tislelizumab in patients with advanced solid tumours: results from the dose-expansion stage of a multicentre, open-label, phase I trial. Friedlander, M., Mileshkin, L., Lombard, J., et al.[2023]

The combination of pamiparib (a PARP inhibitor) and tislelizumab (an anti-PD-1 antibody) was generally well tolerated in a study of 49 patients with advanced solid tumors, with a recommended phase 2 dose established as tislelizumab 200 mg every 3 weeks plus pamiparib 40 mg twice daily.

Out of the participants, 20% achieved an objective response, including two complete responses, indicating that this combination therapy may provide clinical benefits and warrants further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pamiparib in combination with tislelizumab in patients with advanced solid tumours: results from the dose-escalation stage of a multicentre, open-label, phase 1a/b trial. Friedlander, M., Meniawy, T., Markman, B., et al.[2020]

Pamiparib, administered at 60 mg twice a day, demonstrated significant antitumor activity in patients with advanced ovarian cancer, achieving an objective response rate of 64.6% in those with platinum-sensitive ovarian cancer (PSOC) and 31.6% in platinum-resistant ovarian cancer (PROC).

The treatment was well-tolerated, with a manageable safety profile, although some patients experienced grade ≥3 adverse events, primarily hematologic toxicities like anemia and decreased neutrophil count.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pamiparib Monotherapy for Patients with Germline BRCA1/2-Mutated Ovarian Cancer Previously Treated with at Least Two Lines of Chemotherapy: A Multicenter, Open-Label, Phase II Study. Wu, X., Zhu, J., Wang, J., et al.[2023]

The combination of the AKT inhibitor ipatasertib with paclitaxel significantly improved progression-free survival in patients with metastatic triple-negative breast cancer, especially in those with specific genetic alterations (PIK3CA/AKT1/PTEN).

Circulating tumor DNA (ctDNA) analysis showed that lower levels of ctDNA during treatment were associated with better outcomes, indicating that ctDNA could be a useful tool for monitoring treatment response and prognosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Circulating Tumor DNA and Biomarker Analyses From the LOTUS Randomized Trial of First-Line Ipatasertib and Paclitaxel for Metastatic Triple-Negative Breast Cancer. Wongchenko, MJ., Kim, SB., Saura, C., et al.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05038839?intr=BGB-290&aggFilters=studyType:int&viewType=Table&rank=8

NCT05038839 | Cabozantinib and Pamiparib for the ... This phase I trial finds the best dose and side effects of cabozantinib and pamiparib in treating patients with solid tumors that have spread to other ...

2. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2021-03248

Cabozantinib and Pamiparib for the Treatment of ... This phase I trial finds the best dose and side effects of cabozantinib and pamiparib in treating patients with solid tumors that have spread to other places ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39107157/

CARINA Study Results Conclusion: DoT for 2L treatment was numerically better for cabozantinib than for other therapies, and after 1L CPI-CPI therapy than after 1L TKI-CPI therapy.

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7926018/

Cabozantinib real‐world effectiveness in the first‐through ... For patients treated with 1L PD(L)1 combination (n = 31), 2L cabozantinib had ORR of 22%, median TTF of 5.4 months, and median OS (mOS) of 17.4 ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT01588821?term=xl-184%20,%20prostate%20cancer&viewType=Table&rank=2&tab=results

Study Results | Cabozantinib in Advanced Solid ... An unfavorable change in the health of a participant, including abnormal laboratory findings, that happens during a clinical study or within a certain amount of ...

6. withpower.com withpower.com/trial/phase-1-neoplasms-9-2021-29737

Cabozantinib + Pamiparib for Advanced Cancer Pamiparib has shown antitumor activity and safety in patients with advanced solid tumors and ovarian cancer, suggesting it may be effective in treating other ...

7. annalsofoncology.org annalsofoncology.org/article/S0923-7534(24)02215-4/fulltext

629P Phase I study of pamiparib and cabozantinib in ... Preliminary evidence in this study showed that the treatment with oral pamiparib 60 mg BID and cabozantinib 40 mg QD was well-tolerated and has yielded modest ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11332639/

The efficacy and safety of cabozantinib in patients ... Positive results were observed for cabozantinib, with a 40% reduction in disease progression or death and a 23% tumor response rate compared to ...