The University of Texas MD Anderson Cancer Center will join with Pfizer to study novel combinations of three of the pharma giant’s immuno-oncology candidates and other Pfizer treatments for solid and blood cancers, the partners said today, through a collaboration whose value was not disclosed.
The collaboration will consist of multiple studies—the first of which is envisioned to enroll up to 188 patients with solid tumors, who will be placed in seven different treatment groups of immuno-oncology agents alone or immuno-oncology agents combined with radiotherapy.
The second study will include eight different treatment groups and is expected to enroll up to 159 patients with acute myeloid leukemia (AML) undergoing treatment at MD Anderson. Three additional studies are planned to evaluate investigational Pfizer agents in patients with blood cancers. The majority of the trials are expected to open in late 2017.
“This alliance aims to define patients with solid tumors who may benefit from immunotherapy and to develop therapy resistance strategies,” Aung Naing, M.D., associate professor of investigational cancer therapeutics, MD Anderson, said in a statement. “The studies are designed to hone in on specific combinations and tumor types, and explore unique mechanisms of response and resistance to immunotherapies.
Dr. Naing will lead the solid tumor program while Naval Daver, M.D., assistant professor of leukemia at MD Anderson, will head the blood cancer clinical studies, which Dr. Naver said would involve an accelerated series of Phase Ib combination immunotherapy trials for AML and solid tumors.
A joint steering committee consisting of representatives of MD Anderson and Pfizer will oversee the collaboration, which the partners said will include—but not be limited to—five Pfizer cancer candidates.
One of them is Bavencio® (avelumab), which has been co-developed by Pfizer through an up-to-$2.85 billion alliance with Merck KGaA launched in 2014. Bavencio won two FDA approvals this year: The programmed death-ligand 1 (PD-L1) checkpoint inhibitor gained its first U.S. authorization in March for metastatic Merkel cell carcinoma in adults and children aged 12 years and over. Bavencio was additionally approved in May for patients with locally advanced or metastatic urothelial carcinoma (UC) whose disease progressed during or following platinum-containing chemotherapy therapy, or who exhibit disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy.
Another approved cancer treatment being studied by MD Anderson and Pfizer will be Mylotarg™ (gemtuzumab ozogamicin), a CD33-directed antibody–drug conjugate approved September 1 by the FDA for adults with newly diagnosed CD33-positive AML, and adults and children 2 years and older with relapsed or refractory CD33-positive AML.1.
That approval marked the second go-round for Mylotarg; in 2000, Mylotarg won authorization at a higher dose as a single agent in patients with CD33-positive AML who had experienced their first relapse and were 60 years or older and who were not considered candidates for other cytotoxic chemotherapy. But after a confirmatory trial failed to show clinical benefit and did show a higher rate of fatal toxicity compared to chemotherapy, Pfizer voluntarily withdrew the drug in the U.S. in 2010.
Mylotarg is the first therapy to win FDA approval for an indication that includes pediatric AML—and according to Pfizer, the only AML therapy that targets CD33, an antigen expressed on AML cells in up to 90% of patients.
Also being assessed is glasdegib (PF-04449913), a Phase II oral smoothened (SMO) inhibitor included in six studies recruiting patients. These include a Phase II study (NCT01841333) in AML patients with high risk of post-allogeneic stem cell transplantation relapse; a Phase II study (NCT02226172) in patients with primary or secondary myelofibrosis; a Phase I combination study (NCT02367456) with azacitidine in first-line AML, myelodysplastic syndromes (MDS), and chronic myelomonocytic leukemia patients, and a Phase I study (NCT02038777) in Japanese patients alone or with low-dose ara-C or cytarabine and daunorubicin in previously untreated patients with AML or high-risk MDS.
Two Phase I Pfizer pipeline candidates are also to be studied through the collaboration:
- PF-04518600, a Phase I OX40 (CD-134) agonist under study as monotherapy and in combinations with Pfizer’s Inlyta® (axitinib) (NCT03092856) Bavencio (NCT03217747), utomilumab (NCT02315066), and both Bavencio and utomilumab (NCT02554812).
- Utomilumab (PF-05082566), a Phase I 4-1BB (CD-137) agonist in numerous studies, including combinations with Bavencio and PF-04518600 (NCT02554812 and NCT03217747); utomilumab (NCT02554812); Merck & Co.’s marketed cancer immunotherapy Keytruda® (pembrolizumab) (NCT02179918, completed in March); Genentech/Biogen’s Rituxan® (rituximab) (NCT01307267); Rituxan and Bavencio (NCT02951156) and Kyowa Hakko Kirin’s anti-CCR4 antibody Poteligeo® (mogamulizumab) (NCT02444793).