AB801 for Advanced Cancer

(ARC-27 Trial)

Recruiting at 13 trial locations

Overseen By Medical Director

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Arcus Biosciences, Inc.

Must not be taking: Immunosuppressants, Corticosteroids

Disqualifiers: Autoimmune diseases, Prolonged QT interval, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 8-12 weeks

91 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial requires that you stop taking systemic immunosuppressive medications (like corticosteroids and methotrexate) at least 2 weeks before starting the study treatment. The protocol does not specify about other medications, so it's best to discuss your current medications with the study team.

What data supports the effectiveness of the drug AB801 for advanced cancer?

Research shows that docetaxel, a component of AB801, has been effective in treating various cancers, including breast and lung cancer, often improving survival rates and response rates when used alone or in combination with other drugs. ^{1 2 3 4 5}

What safety data exists for docetaxel (Taxotere) in humans?

Docetaxel, also known as Taxotere, has been associated with several side effects, including severe allergic reactions, low white blood cell counts, fluid retention, and nerve damage. Some patients have experienced serious heart and breathing problems, and skin reactions have been more common with certain formulations. ^{6 7 8 9 10}

What makes the drug AB801 unique for treating advanced cancer?

The treatment AB801 combines docetaxel, a well-established chemotherapy drug known for its effectiveness in various cancers, with zimberelimab, an immune checkpoint inhibitor that helps the immune system attack cancer cells. This combination aims to enhance the overall anti-cancer effect by using both chemotherapy and immunotherapy strategies. ^{4 11 12 13 14}

What is the purpose of this trial?

The primary purpose of this study is to assess the safety and tolerability of AB801 in participants with advanced malignancies, and to determine a recommended AB801 dose for expansion.

Research Team

Medical Director

Principal Investigator

Arcus Biosciences

Eligibility Criteria

This trial is for adults with certain advanced cancers like lung, colorectal, breast, ovarian, kidney, head and neck, or bladder cancer that's worsened despite treatment. They should have no standard care options left or can't tolerate them. Participants need at least one measurable tumor and must be in good physical condition (ECOG score 0-1).

Inclusion Criteria

My cancer has not responded to treatment and there are no standard treatments left for me.

My cancer does not have specific genetic changes and is not a mix of small-cell and squamous types.

I've had treatment with platinum-based chemo and PD-(L)1 inhibitor for advanced cancer.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive AB801 orally daily in various dose levels to assess safety and tolerability

8-12 weeks

Dose Expansion

Participants with NSCLC receive AB801 in combination with docetaxel to determine recommended dose for expansion

8-12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• AB801
• Docetaxel
• Zimberelimab

Trial Overview The study tests AB801 alone and combined with other drugs (Zimberelimab and Docetaxel) to find a safe dose for people with advanced malignancies. It aims to see how well participants tolerate AB801 and determine the best dose for further research.

Participant Groups

Group I: Dose Expansion Cohort - AB801 + Docetaxel Experimental Treatment 2 Interventions

Participants with NSCLC will receive AB801 orally in combination with docetaxel IV infusion

Group II: Dose Escalation Cohort 7 - AB801 tablets Dose Level 7 Experimental Treatment 1 Intervention

Participants will receive AB801 orally daily

Group III: Dose Escalation Cohort 6 - AB801 tablets Dose Level 6 Experimental Treatment 1 Intervention

Participants will receive AB801 orally daily

Group IV: Dose Escalation Cohort 5 - AB801 tablets Dose Level 5 Experimental Treatment 1 Intervention

Participants will receive AB801 orally daily

Group V: Dose Escalation Cohort 4 - AB801 capsule Dose Level 4 Experimental Treatment 1 Intervention

Participants will receive AB801 orally daily

Group VI: Dose Escalation Cohort 3 - AB801 capsule Dose Level 3 Experimental Treatment 1 Intervention

Participants will receive AB801 orally daily

Group VII: Dose Escalation Cohort 2 - AB801 capsule Dose Level 2 Experimental Treatment 1 Intervention

Participants will receive AB801 orally daily

Group VIII: Dose Escalation Cohort 1 - AB801 capsule Dose Level 1 Experimental Treatment 1 Intervention

Participants will receive AB801 orally daily

Who Is Running the Clinical Trial?

Arcus Biosciences, Inc.

Lead Sponsor

Trials

44

Recruited

7,500+

Findings from Research

In a phase III trial involving 511 patients with advanced breast cancer, the combination of capecitabine and docetaxel significantly improved progression-free and overall survival compared to single-agent docetaxel, with a median survival of 14.5 months versus 11.5 months.

Patients who received single-agent docetaxel followed by capecitabine had a notably better survival rate compared to those who received other poststudy chemotherapy, indicating that sequential therapy with these agents may enhance treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Survival benefit with capecitabine/docetaxel versus docetaxel alone: analysis of therapy in a randomized phase III trial. Miles, D., Vukelja, S., Moiseyenko, V., et al.[2019]

In a phase II trial involving 76 patients with HER2/neu-negative metastatic breast cancer, the combination of docetaxel and bevacizumab showed a promising objective response rate of 51%, with a median overall survival of 26.3 months.

The treatment was generally well tolerated, with manageable side effects, although common grade 3/4 adverse events included neutropenia (33%) and leukopenia/lymphopenia (25%).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase II trial of docetaxel with bevacizumab as first-line therapy for HER2-negative metastatic breast cancer (TORI B01). Hurvitz, SA., Allen, HJ., Moroose, RL., et al.[2020]

Docetaxel has shown a high overall response rate of approximately 60% in phase II studies for metastatic breast cancer and has demonstrated superior efficacy compared to doxorubicin, making it a promising candidate for adjuvant therapy.

The combination of docetaxel with doxorubicin is particularly promising for treating early-stage breast cancer, as it has not been associated with significant heart-related side effects, unlike other combinations, and large phase II trials are currently underway to assess its effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A review of the efficacy and safety of docetaxel as monotherapy in metastatic breast cancer. Crown, J.[2018]

Docetaxel has shown impressive efficacy in treating various cancers, including breast cancer, non-small-cell lung cancer (NSCLC), and ovarian cancer, outperforming or matching established chemotherapy regimens in phase III trials involving multiple tumor types.

In addition to its effectiveness, docetaxel is often associated with an improved safety profile, and it has demonstrated a survival benefit in previously challenging cases, such as anthracycline-resistant breast cancer and second-line NSCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The current status of docetaxel in solid tumors. An M. D. Anderson Cancer Center Review. Hong, WK.[2018]

In a study of 43 patients with anthracycline-resistant advanced breast carcinoma, the combination of docetaxel and capecitabine resulted in a significant overall response rate of 62.8%, with a median survival time of 15 months.

The treatment was found to be effective and tolerable, although it did cause gastrointestinal and hematological toxicities, indicating that while it improves quality of life, monitoring for side effects is important.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Combination of docetaxel and capecitabine for the treatment of anthracycline-resistant advanced breast carcinoma]. Zhang, JD., Shao, ZY.[2018]

Docetaxel, an anti-microtubule agent, has demonstrated significant effectiveness in treating metastatic breast cancer, as confirmed by Phase I and II trials.

However, this case report highlights a rare but serious side effect: a rapid onset of diffuse scleroderma-like illness in a patient undergoing treatment, emphasizing the need for monitoring adverse reactions during therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Scleroderma in association with the use of docetaxel (taxotere) for breast cancer. Hassett, G., Harnett, P., Manolios, N.[2018]

In a phase II study involving 58 patients with advanced gastric cancer, the combination of docetaxel, fluorouracil, and leucovorin (TFL) showed a moderate overall response rate of 26%, with 4 complete and 11 partial responses observed.

The TFL regimen was found to have manageable toxicity, with neutropenia being the most common severe side effect (30% of patients), and no toxic deaths reported, indicating a favorable safety profile for this chemotherapy combination.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combination docetaxel (Taxotere), fluorouracil, and leucovorin (TFL), as first-line chemotherapy in advanced gastric cancer: a Hellenic Cooperative Oncology Group phase II study. Papakostas, P., Tsavdaridis, D., Kosmidis, P., et al.[2022]

Docetaxel, an FDA-approved chemotherapy for various cancers, can cause severe side effects, including life-threatening reactions such as anaphylaxis and cardiac-respiratory arrest, as demonstrated in a case involving a 62-year-old patient with metastatic prostate cancer.

Despite premedication with corticosteroids, the patient experienced a cardiac-respiratory arrest within 15 minutes of receiving docetaxel, highlighting the need for careful monitoring during treatment, especially in patients with pre-existing conditions like atrial fibrillation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Docetaxel-induced cardiac-respiratory arrest in a patient with chronic atrial fibrillation. Huq, M., Balvanz, TM., Mambourg, S.[2019]

In a study of 97 breast cancer patients, those treated with the one-vial ready-to-use formulation (T1V) of Taxotere received a significantly lower dose of the drug compared to those treated with the two-vial preparation (T2V), indicating potential issues with dose delivery.

Patients using the T1V formulation experienced higher rates of cutaneous and neurological toxicities, as well as a greater frequency of grade 3 toxicities, suggesting that the new formulation may have a less favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dose intensity and toxicity associated with Taxotere formulation: a retrospective study in a population of breast cancer patients treated with docetaxel as an adjuvant or neoadjuvant chemotherapy. Chanat, C., Delbaldo, C., Denis, J., et al.[2018]

In a study of 27 patients with inoperable non-small-cell lung cancer (NSCLC) who had previously received platinum-based chemotherapy, docetaxel showed a partial response rate of 24%, indicating its effectiveness as a treatment option.

The main side effect observed was severe neutropenia in 75% of patients, highlighting the need for careful monitoring of blood cell counts during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Efficacy of docetaxel in non-small cell lung cancer patients previously treated with platinum-containing chemotherapy. French Group of Pneumo-Cancerology]. Robinet, G., Thomas, P., Pérol, M., et al.[2018]

In a study involving 44 patients with advanced or metastatic carcinoma, CKD-810 (a test form of docetaxel) showed equivalent pharmacokinetics and safety compared to the reference docetaxel (Taxotere), with no significant differences in key parameters like maximum plasma concentration and time to reach that concentration.

Both CKD-810 and reference docetaxel had similar rates of severe toxicity, with neutropenia being the most common side effect, indicating that CKD-810 is a safe alternative for patients undergoing treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Open-label, randomized, single-dose, crossover study to evaluate the pharmacokinetics and safety differences between two docetaxel products, CKD-810 and Taxotere injection, in patients with advanced solid cancer. Cho, EK., Park, JY., Lee, KH., et al.[2018]

Docetaxel is an effective treatment for non-small cell lung cancer (NSCLC), showing comparable efficacy to newer platinum-based therapies in advanced stages, and has been approved for use in this context.

Clinical trials are ongoing to explore the best ways to combine docetaxel with other treatments, such as thoracic radiotherapy and molecularly targeted agents, to enhance its effectiveness in various stages of NSCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Docetaxel in non-small cell lung cancer: a review. Davies, AM., Lara, PN., Mack, PC., et al.[2019]

Docetaxel is an effective treatment for advanced non-small cell lung cancer (NSCLC), showing survival benefits in both first- and second-line therapy, and is comparable or superior to other platinum-based chemotherapy options.

The drug has a manageable toxicity profile and has shown promising results when combined with novel targeted agents in Phase II studies, indicating its versatility in treatment regimens.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Docetaxel in advanced non-small cell lung cancer. Wakelee, H., Ramalingam, S., Belani, CP.[2018]

Docetaxel shows significant antitumor activity in advanced non-small cell lung cancer (NSCLC), with objective response rates of 33-38% in previously untreated patients and 21-27% in those who had prior chemotherapy, based on four Phase II studies involving a total of 171 patients.

The most common side effect was neutropenia, along with other non-hematological adverse events like hypersensitivity reactions and skin rash, indicating that while docetaxel is effective, monitoring for side effects is important.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Docetaxel in stage III and IV non-small cell lung cancer. Rigas, JR.[2019]

References

1. United States pubmed.ncbi.nlm.nih.gov

Survival benefit with capecitabine/docetaxel versus docetaxel alone: analysis of therapy in a randomized phase III trial. [2019]

2. United States pubmed.ncbi.nlm.nih.gov

A phase II trial of docetaxel with bevacizumab as first-line therapy for HER2-negative metastatic breast cancer (TORI B01). [2020]

3. United States pubmed.ncbi.nlm.nih.gov

A review of the efficacy and safety of docetaxel as monotherapy in metastatic breast cancer. [2018]

4. United States pubmed.ncbi.nlm.nih.gov

The current status of docetaxel in solid tumors. An M. D. Anderson Cancer Center Review. [2018]

5. China pubmed.ncbi.nlm.nih.gov

[Combination of docetaxel and capecitabine for the treatment of anthracycline-resistant advanced breast carcinoma]. [2018]

6. Italy pubmed.ncbi.nlm.nih.gov

Scleroderma in association with the use of docetaxel (taxotere) for breast cancer. [2018]

7. Japan pubmed.ncbi.nlm.nih.gov

Combination docetaxel (Taxotere), fluorouracil, and leucovorin (TFL), as first-line chemotherapy in advanced gastric cancer: a Hellenic Cooperative Oncology Group phase II study. [2022]

8. England pubmed.ncbi.nlm.nih.gov

Docetaxel-induced cardiac-respiratory arrest in a patient with chronic atrial fibrillation. [2019]

9. England pubmed.ncbi.nlm.nih.gov

Dose intensity and toxicity associated with Taxotere formulation: a retrospective study in a population of breast cancer patients treated with docetaxel as an adjuvant or neoadjuvant chemotherapy. [2018]

10. France pubmed.ncbi.nlm.nih.gov

[Efficacy of docetaxel in non-small cell lung cancer patients previously treated with platinum-containing chemotherapy. French Group of Pneumo-Cancerology]. [2018]

11. Germany pubmed.ncbi.nlm.nih.gov

Open-label, randomized, single-dose, crossover study to evaluate the pharmacokinetics and safety differences between two docetaxel products, CKD-810 and Taxotere injection, in patients with advanced solid cancer. [2018]

12. England pubmed.ncbi.nlm.nih.gov

Docetaxel in non-small cell lung cancer: a review. [2019]

13. England pubmed.ncbi.nlm.nih.gov

Docetaxel in advanced non-small cell lung cancer. [2018]

14. England pubmed.ncbi.nlm.nih.gov

Docetaxel in stage III and IV non-small cell lung cancer. [2019]