A Study to Learn About the Study Medicine PF-07934040 When Given Alone or With Other Anti-cancer Therapies in People With Advanced Solid Tumors That Have a Genetic Mutation.

Carcinoma, Non-Small-Cell Lung Clinical Trial

Official title:

A Phase 1 Open-Label Study of PF-07934040 as a Single Agent and in Combination With Other Targeted Agents in Participants With Advanced Solid Tumors Harboring Mutations in the KRAS Gene

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06447662
• Other study ID #: C5421001
• Status: Not yet recruiting
• Phase: Phase 1
• Start date: July 28, 2024
• Est. completion date: July 12, 2028

Study information

• Verified date: June 2024
• Source: Pfizer
• Contact: Pfizer CT.gov Call Center
• Phone: 1-800-718-1021
• Email: ClinicalTrials.gov_Inquiries[@]pfizer.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to learn about the safety and effects of the study medicine alone or when given together with other anti-cancer therapies. This study also aims to find the best dose.

This study is seeking participants who have solid tumors (a mass of abnormal cells that forms a lump or growth in the body) that:

• are advanced (cancer that doesn't disappear or stay away with treatment) and

• have a KRAS gene mutation (a change in the DNA of the KRAS gene that can cause cells to grow in very high numbers).

This includes (but limited to) the following cancer types:

Non-Small Cell Lung Cancer (NSCLC): It's a type of lung cancer where the cells grow slowly but often spread to other parts of the body.

Colorectal Cancer (CRC): This is a disease where cells in the colon (a part of large intestine) or rectum grow out of control.

Pancreatic ductal adenocarcinoma (PDAC): This is a cancer that starts in the ducts of the pancreas but can spread quickly to other parts of the body. Pancreas is a long, flat gland that lies in the abdomen behind the stomach. Pancreas creates enzymes that help with digestion. It also makes hormones that can help control your blood sugar levels.

All participants in this study will take the study medication (PF-07934040) as pill by mouth twice a day repeating for 21-day or 28-day cycles.

Depending on which part of the study participants are enrolled into they will receive the study medication (PF-07934040 alone or in combination with other anti-cancer medications). These anti-cancer medications will be given in the study clinic by intravenous (IV) that is directly injected into the veins at various times (depending on the treatment) during the 21-day or 28-day cycle.

Participants can continue to take the study medication (PF-07329640) and the combination anti-cancer therapy until their cancer is no longer responding.

The study will look at the experiences of people receiving the study medicines. This will help see if the study medicines are safe and effective.

Participants will be involved in this study for up to 4 years. During this time, they will come into the clinic between 1 to 4 times in each 21-day or 28-day cycle. After they have stopped taking the study medication (at about at 2 years) they will be followed for another two years to see how they are doing.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 330
• Est. completion date: July 12, 2028
• Est. primary completion date: July 13, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Histological or cytological diagnosis of advanced, unresectable, and/or metastatic or relapsed/refractory solid tumor.

ECOG PS 0 or 1

• Presence of at least 1 measurable lesion based on RECIST version 1.1 that has not been previously irradiated.

• Documentation of mutated KRAS gene

1. PDAC, CRC, Other tumor types: Confirmed KRAS mutation, any variant

2. NSCLC: Confirmed KRAS mutation, any variant except previously treated G12C. If driver mutation, must have failed precision medicine therapy [eg, inhibitors of epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), c-ros oncogene 1 (ROS1), and others].

• Part 1 and Part 2a: Participant must have progressed on standard treatment(s) for which no additional, effective therapy is available.

1. PDAC (2-3L): Participants must have received and radiologically progressed on prior lines of systemic therapy for metastatic pancreatic adenocarcinoma. If participants received prior neoadjuvant or adjuvant chemotherapy and progressed within 6 months of the last dose, then this should be considered as a prior line of systemic therapy.

2. NSCLC (2-3L): Participants must have received prior lines of anti-cancer treatment and progressed on at least a platinum-containing chemotherapy regimen and checkpoint inhibitor therapy; for participants with EGFR, ALK, or other genomic tumor alterations, participants must have progressed on approved therapy for these alterations.

3. CRC (2-3L): Participants must have had one or two prior systemic treatment regimens for mCRC. For either one or two prior treatments, these regimens must have included a fluoropyrimidine, oxaliplatin, or irinotecan; for one prior treatment, exposure to VEGF/VEGF receptor (VEGFR) inhibitor is optional;

4. Other tumors: Participants, in the judgment of the investigator, must have progressed or become intolerant to all available standard therapies, or have refused such therapy.

• Part 2b:

1. PDAC (1L) Cohort A2: Participants must not have received prior chemotherapy for metastatic disease. Participant could have received neoadjuvant therapy, adjuvant therapy, or adjuvant chemo-radiotherapy, as long as relapse did not occur within 6 months of completing these forms of adjuvant treatment. If so, the relapse within 6 months would be considered a line of therapy; the participant would be considered 2L, and not 1L.

2. CRC (2-3L) Cohort B2: Participants must have had one or two prior systemic treatment regimens for mCRC. For either one or two prior treatments, these regimens must have included a fluoropyrimidine, irinotecan, oxaliplatin; for one prior treatment, exposure to a VEGF/VEGF receptor (VEGFR) inhibitor is optional.

3. CRC (1L) Cohort B3: Participants must not have had prior chemotherapy for advanced or metastatic disease. Participant could have received adjuvant chemotherapy or adjuvant chemo-radiotherapy, as long as relapse did not occur within 6 months of complete of adjuvant therapy. If so, the relapse within 6 months would be considered a line of therapy; the participant would be considered 2L, and not 1L.

4. NSCLC (1L) Cohort C2: Participants must have a TPS =50% and must not have received prior systemic treatment setting.

5. NSCLC (1L) Cohort C3: Participants with any TPS and must not have received prior systemic treatment setting.

Exclusion Criteria:

• Active or history of pneumonitis/ILD, pulmonary fibrosis requiring treatment with systemic steroid therapy, including evidence to suggest pneumonitis/ILD on baseline assessments including imaging.

• Diagnosis of immunodeficiency or an active autoimmune disease that require systemic treatment with chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy in the past 2 years.

• Sensory peripheral neuropathy =Grade 2

• Active or history of clinically significant gastrointestinal (GI) disease (including but not limited to inflammatory GI disease [eg, ulcerative colitis, Crohn's disease, inflammatory bowel disease], immune-mediated colitis, peptic ulcer disease, GI bleeding, chronic diarrhea) and other conditions that are unresolved and/or may increase the risk associated with study participation or study treatment administration.

• Active bleeding disorder, including GI bleeding, as evidenced by hematemesis, significant hemoptysis or melena in the past 6 months.

• Major surgery or completion of radiation therapy =4 weeks prior to enrollment/randomization or radiation therapy that included >30% of the bone marrow.

• Known sensitivity or contraindication to any component of study intervention (PF 07934040, gemcitabine, nab-paclitaxel, cetuximab, bevacizumab, FOLFOX, 5-FU, pembrolizumab, cisplatin, carboplatin, pemetrexed, SHP2 inhibitor(s), cyclin-dependent kinase (CDK) inhibitor(s), antibody drug conjugates (ADCs) or EGFR inhibitor(s)).

• Hematologic abnormalities.

• Renal impairment.

• Hepatic abnormalities.

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Non-Small-Cell Lung
• Carcinoma, Pancreatic Ductal
• Colorectal Neoplasms
• Neoplasms

Intervention

Drug:
• PF-07934040
panKRAS inhibitor

Combination Product:
• Gemcitabine
Chemotherapy (antimetabolite)
• Nab-paclitaxel
Taxane-type Chemotherapy
• Cetuximab
Monoclonal Antibody (EGFR Inhibitor)
• Fluorouracil
Part of FOLFOX chemotherapy regimen cytotoxic chemotherapy (antimetabolite and pyrimidine analog)
• Oxaliplatin
Part of FOLFOX Chemotherapy Regimen platinum based compound (alkylating agent)
• Leucovorin
Part of FOLFOX chemotherapy regimen Folic Acid Analog
• Bevacizumab
VEG-F inhibitor
• Pembrolizumab
immune checkpoint inhibitor (PD-1 inhibitor)
• pemetrexed
Can be used in Platinum-based Chemotherapy regimen Antimetabolite
• Cisplatin
Can be used as part of Platinum-based chemotherapy regimen Platinum-based antineoplastic (alkylating agent)
• Paclitaxel
Can be used in Platinum-based chemotherapy regimen Taxane
• Carboplatin
Can be used as part of a platinum-based chemotherapy regimen platinum containing compound (alkylating agent)

Locations

Country	Name	City	State
Puerto Rico	Pan American Center for Oncology Trials, LLC	Rio Piedras

Sponsors (1)

Lead Sponsor	Collaborator
Pfizer

Country where clinical trial is conducted

Puerto Rico, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Part 1 & 2: Incidence of Adverse Events (AEs)	An adverse event (AE) was any untoward medical occurrence in a participant who received study medication without regard to possibility of causal relationship to it. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/ incapacity; congenital anomaly. AEs included both serious and all non-serious AEs.	Start of treatment up to 30 days after last dose or start of new anticancer therapy (whichever occurs first)
Primary	PART 1 & 2: Number of participants with laboratory abnormalities	Number of participants with laboratory test abnormalities. Laboratory test parameters included hematology, coagulation, liver function, renal function, electrolytes, clinical chemistry, and urinalysis (dipstick and microscopy).	From start of treatment up to 30 days after last dose or start of new anticancer therapy, whichever occurred first
Primary	Part 1: Number of participants with Dose-limiting toxicities (DLT)	Any of the prespecified AEs that are attributable to one, the other, or both study treatments, occurring in the DLT observation period are considered DLTs, excluding toxicities clearly due to underlying disease or extraneous causes	Baseline up to 28 days
Primary	Part 2: Objective Response - Number of Participants With Objective Response (alone or in combination)	Percentage of participants with objective response-based assessment of complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST v1.1) for overall response rate (ORR), progression free survival (PFS), and overall survivor (OS) assessed by the Investigator.	Baseline and every 8 to 12 weeks through time of confirmed disease progression, death, unacceptable toxicity, or through study completion, approximately 2 years'
Secondary	Part 1 & 2: Maximum Observed Serum Concentration (Cmax)	Evaluate the single and multiple dose PK of PF-07934040 as monotherapy, or in combination with other anti-tumor agents.	baseline through end of Cycle 1 (All cycles are 28 days except part 2b Cohort C2 which are 21 days)
Secondary	Part 1& 2: Time to Reach Maximum Observed Serum Concentration (Tmax)	Evaluate the single and multiple dose PK of PF-07934040 as monotherapy, or in combination with other anti-tumor agents.	Baseline through end of Cycle 1 (All cycles are 28 days except part 2b Cohort C2 which are 21 days)
Secondary	Part 1 & 2: Serum Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast)	Evaluate the single and multiple dose PK of PF-07934040 as monotherapy, or in combination with other anti-tumor agents.	Baseline through end of Cycle 1 (All cycles are 28 days except part 2b Cohort C2 which are 21 days)
Secondary	Part 1 & 2: Changes in pERK levels	Evaluates the intended mechanism of action (MoA) modulation of KRAS inhibition and target engagement effect of PF-07934040 in peripheral blood of participants with advanced solid tumor malignancies.	Baseline through end of Cycle 1 (All cycles are 28 days except part 2b Cohort C2 which are 21 days)
Secondary	Part 1: Objective Response - Number of Participants With Objective Response	Percentage of participants with objective response-based assessment of complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST v1.1) assessed by the Investigator including overall response rate (ORR), progression free survival (PFS), and overall survival (OS).	Baseline and every 8 to 12 weeks through time of confirmed disease progression, death, unacceptable toxicity, or through study completion, approximately 2 years
Secondary	Part 1: Effect of Food on Cmax	Evaluate the effect of food on Cmax of PF-07934040 as monotherapy.	Baseline through end of Cycle 1 (All cycles are 28 days)
Secondary	Part 1: Effect of Food on Tmax	Evaluate the effect of food on Tmax of PF-07934040 as monotherapy.	Baseline through end of Cycle 1 (All cycles are 28 days)
Secondary	Part 1: Effect of Food on AUClast	Evaluate the effect of food on AUClast of PF-07934040 as monotherapy.	Baseline through end of Cycle 1 (All cycles are 28 days)

External Links

•   To obtain contact information for a study center near you, click here.