Quavonlimab + Pembrolizumab for Advanced Cancer

No longer recruiting at 64 trial locations

Overseen By Toll Free Number

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Merck Sharp & Dohme Corp.

Must not be taking: CTLA-4 agents, PD-1 agents

Disqualifiers: CNS metastases, Active infection, Autoimmune disease, 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the combination of two drugs, quavonlimab and pembrolizumab (also known as KEYTRUDA), to determine their effectiveness in treating advanced cancers. Researchers aim to assess the safety of these drugs, how the body processes them, and their ability to shrink tumors. The trial includes different parts for various cancer types, such as lung cancer (NSCLC) and melanoma, each with a specific focus. Suitable candidates for this trial have advanced cancer, have not responded to other treatments, and have specific types of lung cancer or melanoma that are difficult to treat with current options. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering patients a chance 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 protocol does not specify if you need to stop taking your current medications. However, it mentions that participants should not have had chemotherapy, radiation, or biological cancer therapy within 4 weeks before starting the study treatment, and should not be on any investigational agents. It's best to discuss your specific medications with the trial team.

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

Research has shown that the combination of quavonlimab and pembrolizumab is generally well-tolerated. Specifically, administering 25 mg of quavonlimab every six weeks with pembrolizumab demonstrated a good safety profile, resulting in fewer serious side effects compared to other dosing schedules. This treatment also proved effective against tumors in patients with advanced non-small cell lung cancer.

Pembrolizumab, already approved by the FDA for other cancers, is known for its manageable side effects. While some side effects occur, they are usually mild and controllable. Overall, the safety data for this combination appears promising, especially with ongoing studies in various advanced cancers. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about quavonlimab and pembrolizumab because these treatments offer a novel approach to targeting advanced cancers, including melanoma and non-small cell lung cancer (NSCLC). Unlike traditional chemotherapy that attacks all rapidly dividing cells, these drugs are immunotherapies that work by enhancing the body's own immune system to fight cancer. Quavonlimab is a unique anti-CTLA-4 antibody that can potentially overcome resistance to PD-1/PD-L1 inhibitors like pembrolizumab, offering hope to patients who have not responded well to existing treatments. Additionally, the combination of these two therapies could lead to more effective and durable responses compared to the current standard of care.

What evidence suggests that this trial's treatments could be effective for advanced cancer?

Research has shown that the combination of quavonlimab and pembrolizumab may help treat advanced solid tumors. In this trial, participants will receive varying doses and schedules of quavonlimab and pembrolizumab across different treatment arms. Studies have shown promising results, with 28% to 40% of patients experiencing tumor shrinkage or halted growth. Most patients tolerate the side effects well, indicating that the treatment is generally tolerable. This therapy is being tested to determine its potential benefits for those with difficult-to-treat cancers. ^{1 2 4 5 6}

Who Is on the Research Team?

Medical Director

Principal Investigator

Merck Sharp & Dohme LLC

Are You a Good Fit for This Trial?

This trial is for adults with advanced solid tumors. Participants must have measurable disease, be in good physical condition (ECOG status of 0 or 1), and not pregnant or breastfeeding. They should have tried all other treatments without success, agree to use contraception, and provide a tumor sample. Certain types of cancer patients are excluded, like those with untreated brain metastases or active infections.

Inclusion Criteria

I have an advanced cancer (not lung cancer for certain groups) and cannot or will not receive standard treatments.

For Efficacy Expansion Phase Arms F and G: Have histologically/cytologically-confirmed unresectable Stage III or Stage IV melanoma per American Joint Committee on Cancer (AJCC) staging system version 8, not amenable to local therapy. Have at least 1 measurable lesion by CT or MRI per RECIST 1.1 by BICR. Cutaneous lesions and other superficial lesions are not considered measurable lesions for the purposes of this protocol, but may be considered as non-target lesions. Participants with unresectable Stage III or IV disease must have progressed on treatment with an anti-PD-1/L1 monoclonal antibody (mAb) administered either as monotherapy, or in combination with other checkpoint inhibitors or other therapies (combinations with anti-cytotoxic T-lymphocyte associated protein 4 [CTLA-4] agents will not be allowed). Participants who receive anti-PD-1 therapy as adjuvant treatment following complete resection of Stage III or IV melanoma and have disease recurrence (unresectable loco-regional disease or distant metastases) while on active treatment or within 6 months of stopping anti-PD-1 are eligible. Have submitted pre-trial imaging and provided a baseline tumor sample. Proto-oncogene B-raf (BRAF) V600 mutation-positive melanoma participants should have received targeted therapy for advanced or metastatic disease (eg, BRAF/MEK inhibitor, alone or in combination) prior to enrolling on this study; however, they are not required to progress on this treatment prior to enrollment. BRAF V600E mutation-positive melanoma participants who have NOT received a BRAF inhibitor (either as adjuvant therapy or in the metastatic disease setting) with lactate dehydrogenase (LDH) < local upper limit of normal (ULN), no clinically significant tumor-related symptoms, and absence of rapidly progressing metastatic melanoma. Approximately 10 participants each from Arms F and G will have 2 mandatory biopsies

I have an advanced cancer that has spread, and I can't or won't use treatments that could help.

Exclusion Criteria

For Dose Escalation Cohorts (1-3) and Dose Confirmation Arms (A-E): Has known untreated central nervous system (CNS) metastases. Has known carcinomatous meningitis. Has received any prior immunotherapy and was discontinued from that treatment due to a Grade 3 or higher immune-related adverse events (irAE). Has had a severe hypersensitivity reaction to treatment with any monoclonal antibody or components of the study drug. Has any active infection requiring therapy. Has a history of interstitial lung disease, history of noninfectious pneumonitis that required steroids (or has current pneumonitis), or history of inflammatory bowel disease. Has an active autoimmune disease that has required systemic treatment in the past 2 years. Has clinically significant cardiac disease. Has received a live or live attenuated vaccine within 28 days of planned treatment start. Has known history of human immunodeficiency virus (HIV) and/or known active Hepatitis B or C infections, and/or known to be positive for hepatitis B surface antigen (HBsAg)/ hepatitis B virus (HBV) DNA. Has known psychiatric or substance abuse disorders that would interfere with the participant's ability to cooperate with the requirements of the trial. Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the study, starting with screening and for up to 120 days following cessation of pembrolizumab or pembrolizumab/quavonlimab. Has not fully recovered from any effects of major surgery without significant detectable infection

For Dose Confirmation Phase: Has received previous treatment with another agent targeting programmed cell death protein 1 (PD-1), programmed cell death ligand 1 (PD-L1), or anti PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor. Has had chemotherapy, definitive radiation, or biological cancer therapy within 4 weeks (2 weeks for palliative radiation) prior to the first dose of study therapy, or has not recovered to Common Toxicity Criteria for Adverse Events (CTCAE) Grade 1 or better from any AEs that were due to cancer therapeutics administered more than 4 weeks earlier. Has received lung radiation therapy of >30 Gray (Gy) within 6 months before the first dose of study treatment. Is currently participating and receiving study therapy in a study of an investigational agent or has participated and received study therapy in a study of an investigational agent or has used an investigational device within 28 days of administration of quavonlimab. Has a history of a second malignancy, unless potentially curative treatment has been completed with no evidence of malignancy for 3 years

For Arm F and G (Efficacy Expansion Phase) and Arm K (Coformulation Phase) ONLY: Has known active CNS metastases and/or carcinomatous meningitis. Has not had resolution of anti-PD-1 antibody-related AEs, including immune-mediated AEs back to Grade ≤1 or baseline (not applicable to Arm K). Has not discontinued steroid treatment for an irAE for at least 2 weeks prior to the first dose of study drug (not applicable to Arm K). Has ocular melanoma (not applicable to Arm K). Has mucosal melanoma (not applicable to Arm K). Has had an allogenic tissue/solid organ transplant

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Evaluation of available PK and safety data including dose limiting toxicities (DLTs) with quavonlimab and pembrolizumab

Up to 6 weeks

Dose Confirmation

Gathering additional safety, tolerability, PK, and preliminary efficacy data of quavonlimab in combination with pembrolizumab

Up to 35 cycles (approximately 24 months)

Efficacy Expansion

Gathering preliminary anti-tumor efficacy data for quavonlimab in combination with pembrolizumab and quavonlimab monotherapy

Up to 24 months

Coformulation

Evaluation of the safety and PK of a coformulated product of pembrolizumab/quavonlimab

Up to 24 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 77 months

What Are the Treatments Tested in This Trial?

Interventions

• Pembrolizumab
• Quavonlimab

Trial Overview The study tests escalating doses of Quavonlimab combined with Pembrolizumab on participants with advanced solid tumors to evaluate safety, tolerability, how the body processes the drugs (pharmacokinetics), and initial effectiveness against the tumors.

How Is the Trial Designed?

Group I: Expansion: DL1 Quavonlimab Schedule 2+PDL2 Pembro Schedule 2: Arm F Experimental Treatment 2 Interventions

On Cycle 1, Day 1 of the Efficacy Expansion Phase and during all subsequent cycles, participants with PD-1/PD-L1 refractory melanoma receive quavonlimab at DL1 in combination with pembrolizumab at pembrolizumab dose level 2 (PDL2). Both quavonlimab and pembrolizumab will be administered according to Schedule 2 for up to 24 months on study.

Group II: Expansion: DL1 Quavonlimab Schedule 2 Monotherapy: Arm G Experimental Treatment 1 Intervention

On Cycle 1, Day 1 of the Efficacy Expansion Phase and during all subsequent cycles, participants with PD-1/PD-L1 refractory melanoma receive quavonlimab at DL1 according to Schedule 2 for up to 24 months on study. Participants who demonstrate radiographically confirmed progressive disease in Arm G will be eligible to receive combination therapy with pembrolizumab (crossover).

Group III: Escalation: Dose Level (DL) 1 Quavonlimab + Pembro: Cohort 1 Experimental Treatment 2 Interventions

On Cycle 1, Day 1 of the Dose Escalation Phase, advanced solid tumor participants receive a single monotherapy dose lead-in with quavonlimab at dose level 1 (DL1). On Cycle 2, Day 1, and for 3 subsequent cycles on Day 1 (Cycles 3 to 5), these participants receive quavonlimab at DL1 in combination with pembrolizumab (pembro) at pembrolizumab dose level 1 (PDL1) according to Schedule 1. For all subsequent cycles (starting with Cycle 6), all participants receive pembrolizumab monotherapy according to Schedule 1. Participants will be treated for up to 35 cycles total on study.

Group IV: Escalation: DL 3 Quavonlimab + Pembro: Cohort 3 Experimental Treatment 2 Interventions

On Cycle 1, Day 1 of the Dose Escalation Phase, participants with advanced solid tumors except NSCLC receive a single monotherapy dose lead-in with quavonlimab at DL3. On Cycle 2, Day 1, and for 3 subsequent cycles on Day 1 (Cycles 3 to 5), these participants receive quavonlimab at DL3 in combination with pembrolizumab at PDL1 according to Schedule 1. For all subsequent cycles (starting with Cycle 6), all participants receive pembrolizumab monotherapy according to Schedule 1. Participants will be treated for up to 35 cycles total on study.

Group V: Escalation: DL 2 Quavonlimab + Pembro: Cohort 2 Experimental Treatment 2 Interventions

On Cycle 1, Day 1 of the Dose Escalation Phase, participants with advanced solid tumors except NSCLC receive a single monotherapy dose lead-in with quavonlimab at DL2. On Cycle 2, Day 1, and for 3 subsequent cycles on Day 1 (Cycles 3 to 5), these participants receive quavonlimab at DL2 in combination with pembrolizumab at PDL1 according to Schedule 1. For all subsequent cycles (starting with Cycle 6), all participants receive pembrolizumab monotherapy according to Schedule 1. Participants will be treated for up to 35 cycles total on study.

Group VI: Confirmation: DL 2 Quavonlimab Schedule 2 + Pembro (SCLC): Arm D Experimental Treatment 2 Interventions

On Cycle 1, Day 1 of the Dose Confirmation Phase, participants with SCLC receive quavonlimab at DL2 in combination with pembrolizumab at PDL1. On all subsequent cycles, participants receive pembrolizumab at PDL1 according to Schedule 1 and quavonlimab at DL2 according to Schedule 2. Participants will be treated for up to 35 cycles total on study.

Group VII: Confirmation: DL 2 Quavonlimab Schedule 2 + Pembro (NSCLC): Arm C Experimental Treatment 2 Interventions

On Cycle 1, Day 1 of the Dose Confirmation Phase, participants with NSCLC receive quavonlimab at DL2 in combination with pembrolizumab at PDL1. On all subsequent cycles, participants receive pembrolizumab at PDL1 according to Schedule 1 and at DL2 quavonlimab according to Schedule 2. Participants will be treated for up to 35 cycles total on study.

Group VIII: Confirmation: DL 2 Quavonlimab Schedule 1 + Pembro (NSCLC): Arm E Experimental Treatment 2 Interventions

On Cycle 1, Day 1 of the Dose Confirmation Phase and during all subsequent cycles, participants with NSCLC receive quavonlimab at DL2 in combination with pembrolizumab at PDL1 according to Schedule 1. Participants will be treated for up to 35 cycles total on study.

Group IX: Confirmation: DL 1 Quavonlimab Schedule 2 + Pembro (NSCLC): Arm B Experimental Treatment 2 Interventions

On Cycle 1, Day 1 of the Dose Confirmation Phase, participants with NSCLC receive quavonlimab at DL1 in combination with pembrolizumab at PDL1. On all subsequent cycles, participants receive pembrolizumab at PDL1 according to Schedule 1 and quavonlimab at DL1 according to Schedule 2. Participants will be treated for up to 35 cycles total on study.

Group X: Confirmation: DL 1 Quavonlimab Schedule 1 + Pembro (NSCLC): Arm A Experimental Treatment 2 Interventions

On Cycle 1, Day 1 of the Dose Confirmation Phase and during all subsequent cycles, participants with NSCLC receive quavonlimab at DL1 in combination with pembrolizumab at PDL1, both according to Schedule 1. Participants will be treated for up to 35 cycles total on study.

Group XI: Coformulation: Pembrolizumab/Quavonlimab Schedule 2: Arm I Experimental Treatment 1 Intervention

On Cycle 1, Day 1 of the Coformulation Phase and during all subsequent cycles, participants with advanced/metastatic solid tumors receive pembrolizumab/quavonlimab according to Schedule 2 for up to 24 months on study.

Group XII: Coformulation Phase in China: Pembrolizumab/Quavonlimab Schedule 2: Arm K Experimental Treatment 1 Intervention

On Cycle 1, Day 1 of the Coformulation Phase and during all subsequent cycles, participants in mainland China with advanced solid tumors receive pembrolizumab/quavonlimab according to Schedule 2 for up to 24 months on study.

Pembrolizumab is already approved in United States, European Union, United Kingdom for the following indications:

Approved in United States as KEYTRUDA for:

• Head and neck squamous cell carcinoma (HNSCC) with PD-L1 CPS ≥1
• Melanoma
• Non-small cell lung cancer (NSCLC)
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Hepatocellular carcinoma
• Renal cell carcinoma
• Cervical cancer
• Endometrial carcinoma

Approved in European Union as KEYTRUDA for:

• Head and neck squamous cell carcinoma (HNSCC) with PD-L1 CPS ≥1
• Melanoma
• Non-small cell lung cancer (NSCLC)
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Hepatocellular carcinoma
• Renal cell carcinoma
• Cervical cancer
• Endometrial carcinoma

Approved in United Kingdom as KEYTRUDA for:

• Untreated metastatic or unresectable recurrent head and neck squamous cell carcinoma (HNSCC) with PD-L1 CPS ≥1

Who Is Running the Clinical Trial?

Merck Sharp & Dohme Corp.

Lead Sponsor

Trials

2,287

Recruited

4,582,000+

Chirfi Guindo

Merck Sharp & Dohme Corp.

Chief Medical Officer

Engineering degree from Ecole Centrale de Paris, MBA from New York University Stern School of Business

Robert M. Davis

Merck Sharp & Dohme Corp.

Chief Executive Officer since 2021

J.D. from Northwestern University Pritzker School of Law, MBA from Northwestern University Kellogg Graduate School of Management, Bachelor's in Finance from Miami University

Merck Sharp & Dohme LLC

Lead Sponsor

Trials

4,096

Recruited

5,232,000+

Chirfi Guindo

Merck Sharp & Dohme LLC

Chief Marketing Officer since 2022

Degree in Engineering from Ecole Centrale de Paris, MBA from New York University Stern School of Business

Robert M. Davis

Merck Sharp & Dohme LLC

Chief Executive Officer since 2021

JD from Northwestern University Pritzker School of Law, MBA from Northwestern University Kellogg Graduate School of Management, Bachelor's in Finance from Miami University

Published Research Related to This Trial

In a phase II trial involving 15 patients with resectable non-small cell lung cancer (NSCLC), neoadjuvant treatment with pembrolizumab showed a major pathologic response in 27% of patients, indicating promising antitumor activity before surgery.

The treatment was found to be feasible and safe, with only 33% of patients experiencing moderate adverse events, and no postoperative mortality, suggesting that pembrolizumab does not compromise surgical outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. Eichhorn, F., Klotz, LV., Kriegsmann, M., et al.[2022]

Nivolumab and pembrolizumab are FDA-approved monoclonal antibodies that target PD-1, helping to enhance T cell activity against cancer by blocking the PD-1/PD-L1 interaction, which allows cancer cells to escape immune detection.

Both drugs have shown efficacy across multiple cancer types, including melanoma and non-small cell lung cancer, and are considered interchangeable options for treating these conditions, which may help manage the rising costs of cancer therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab and pembrolizumab: Monoclonal antibodies against programmed cell death-1 (PD-1) that are interchangeable. Prasad, V., Kaestner, V.[2022]

Pembrolizumab (KEYTRUDA) was approved by the FDA for treating unresectable or metastatic melanoma based on two clinical trials involving 1,374 patients, showing significant improvements in overall survival compared to ipilimumab, with hazard ratios indicating a reduced risk of death.

Patients receiving pembrolizumab also experienced significant improvements in progression-free survival, although some immune-mediated adverse reactions like hypothyroidism and pneumonitis were noted, highlighting the importance of monitoring for side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Pembrolizumab for the Treatment of Patients with Unresectable or Metastatic Melanoma. Barone, A., Hazarika, M., Theoret, MR., et al.[2022]

In a phase I study involving 40 patients with extensive-stage small cell lung cancer (SCLC), the combination of quavonlimab and pembrolizumab showed encouraging antitumor activity with an objective response rate (ORR) of 18%, indicating potential effectiveness in treating this aggressive cancer.

The treatment was generally well tolerated, with 80% of patients experiencing treatment-related adverse events, but only 10% facing dose-limiting toxicity, suggesting that the combination therapy has manageable safety profiles.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-cytotoxic T-lymphocyte-associated antigen-4 monoclonal antibody quavonlimab in combination with pembrolizumab: Safety and efficacy from a phase I study in previously treated extensive-stage small cell lung cancer. Cho, BC., Yoh, K., Perets, R., et al.[2021]

Pembrolizumab, a PD-1 inhibitor, has demonstrated clinical effectiveness in treating various solid tumors, particularly in patients with PD-L1-positive non-small-cell lung cancer and unresectable/metastatic melanoma.

Early-phase trials and ongoing studies are focused on further confirming the clinical benefits of pembrolizumab in thoracic malignancies, highlighting its potential as a significant treatment option in cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of thoracic malignancies: current landscape and future directions. Karim, S., Leighl, N.[2017]

Pembrolizumab, an anti-PD-1 antibody, has shown significant efficacy in treating advanced melanoma, demonstrating superior progression-free survival compared to chemotherapy in Phase II trials and improved overall survival in Phase III trials.

The treatment is generally well tolerated with a favorable safety profile, though common side effects include fatigue and rash, while less frequent but serious immune-related adverse events can occur.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab in the management of metastatic melanoma. Spain, L., Younger, E., Hatipoglu, E., et al.[2020]

Pembrolizumab is a monoclonal antibody that effectively blocks the PD-1 receptor on T cells, enhancing their ability to attack cancer cells, particularly in melanoma patients.

In a Phase I study involving 411 patients, pembrolizumab demonstrated high durable response rates with minimal toxicity, indicating its potential as a safe and effective treatment option for melanoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab joins the anti-PD-1 armamentarium in the treatment of melanoma. Hersey, P., Gowrishankar, K.[2017]

Pembrolizumab (Keytruda) is the first anti-PD-1 therapy approved in the US for treating advanced malignant melanoma, specifically for patients who have progressed after prior treatments.

It is designed to target the PD-1 protein, enhancing the immune system's ability to fight cancer, and is currently under review for approval in the EU.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab: first global approval. Poole, RM.[2021]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT03179436

NCT03179436 | Study of Quavonlimab (MK-1308) in ... The purpose of the Efficacy Expansion Phase is to gather preliminary anti-tumor efficacy data for quavonlimab in combination with pembrolizumab as well as for ...

2. merck.com merck.com/news/merck-presents-three-year-survival-data-for-keytruda-pembrolizumab-in-combination-with-chemotherapy-and-updated-phase-1-2-data-for-investigational-quavonlimab-mk-1308-in-combination-with-key/

Merck Presents Three-Year Survival Data for KEYTRUDA ... Quavonlimab is currently being evaluated in combination with KEYTRUDA across multiple solid tumors as part of ongoing Phase 1 and 2 trials. A ...

3. mycancergenome.org mycancergenome.org/content/clinical_trials/NCT03179436/

Clinical Trial: NCT03179436 This study will assess the safety, tolerability, pharmacokinetics (PK), and preliminary efficacy of escalating doses of quavonlimab when used in ...

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/34371366/

Safety and efficacy from a phase I study in previously ... First-line treatment with quavonlimab + pembrolizumab conferred encouraging antitumor activity (objective response rate [ORR], 28%-40%) and was generally well ...

5. annalsofoncology.org annalsofoncology.org/article/S0923-7534(20)43175-8/fulltext

Safety and efficacy of quavonlimab, a novel anti-CTLA-4 ... The combination therapy was safe and tolerable and showed antitumor activity in patients with advanced NSCLC. •. Data from this study led to a ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/33276076/

Safety and efficacy of quavonlimab, a novel anti-CTLA-4 ... Quavonlimab 25 mg Q6W plus pembrolizumab demonstrated similar efficacy and a better safety profile among all quavonlimab doses/schedules ...